Intro To Neuroscience Class Notes

PPT for unit 1
Tuesday, August 27, 2013
12:14 PM
4.
Transmiss...
3. Units of
the Nervo...
2.
Neuroana...
1. Evolution
and the b...
Power Points Page 1
Communication and Adaptation

Tuesday, September 24, 2013
1:19 PM
TEST OCTOBER 15
Communication and adaptation25pts
Development- 18 pts
Drugs and addiction 17 pts
35 MC FIB
3 5-pt short answer
1 10-pt response
Previous lecture review questions

Types of Synapses
Difference between neuroeffector junction and axoaconic synapses
Neuroeffector is axon-to-(organ, muscle, etc)
Axoaxonic from axon terminal to axon terminal to modulate
Neurotransmitter release
Compare and contrast Small molecule NTs and Large Molecule NT's WRT
Synthesis and degradation
Large are produced from big molecule cleaved into smaller ones in cell
body (Pre-propeptide moved down the axon)
Small molecule made by enzymes created in soma and made in axon
Small molecules can experience re-uptake to be reused or degraded by
enzymes
Large molecules degraded by enzymes, no re-uptake
What is unique about glutamate and GABA
Are exclusively inhibitory or excitatory
Only one more enzyme needed to make GABA from Glutamate
Glial cells highly involved in synthesis and re-uptake
Acetylcholine is very involved in
Memory, alzheimers, and motor systems
Nucleus Basalis of Meynert sends Acetylcholine to other brain regions
via large reaching projections
Dopamine in CNS
Reward processes and Motor behavior
Parkinsons disease and addiction
Ionotropic vs Metabotropic receptors
Ionotropic receptor has ion channel embedded into neuron
Metabotropic receptor creates second messengers and complex
processes
NMDA Receptor
Excitatory, need depolarization and glutamate binding to it to open
channel
Chemically and voltaicaly gated
Psychopharmacology
For any drug to be psychoactive it must cross blood brain barrier
Capillaries and blood vessels are sealed shut in brain unless they
can easily pass through membrane
Drugs can act in many places (See PPT slide 16)
Agonist drugs mimic effect of NT
Antagonist drugs block effect of NT
Precursor loading
Increase concentrations of precursor to drive equilibrium further
to products side and create agonist effect
L-DOPA to treat Parkinsons
Inactivate Enzymes
Prevent synthesis of NT's (generally used in research due to nasty
side effects)
Antagonist effect
Block vesicle release (antagonist) facilitate release (agonist effect)
Agonist- Amphetamine (causes release of dopamine)
Cause leaky vesicles
Reserpine- lowers blood pressure by leaking noradrenaline
Intended to act in periphery and relieve hypertension
Side effect causes depression by acting in CNS
Postsynaptic receptors
Morphine is opioid agonist by acting like endogenous opioids
Naltrexone blocks opioid receptors
Blocking reuptake
Test 2 notes Page 2
Blocking reuptake
Agonist effect so that more NT is in synapse and you facilitate
effect
Cocaine and amphetamine block dopamine transporter
SSRI's Selective serotonin reuptake inhibitors
Inactivate breakdown enzyme
Agnoist effect so that more NT is in synapse
Stimulate autoreceptor
Most neurons release NT and have receptor for that NT on axon
terminal
Negative feedback loop to keep levels constant
By stimulating autoreceptor you block synthesis
LSD stimulates serotonin autoreceptors
Hormones
Posterior pituitary
Controlled by hypothalamus
Direct neural connection to PP
Anterior Pituitary
Connected to hypothalamus by capillary beds, glandular tissue to
synthesize hormones
Releasing Hormones
Peptides released by hypothalamus, increase or decrease release
from Anterior pituitary
Hormones are released into blood stream so they go everywhere in
body
Receptors throughout body including brain
"diffuse NT's" very global effects and multiple possible effects
depending on what organ system they act on
Involvement in hormone secretions
Feedback loops
Control amt of hormone released
Generally a negative feedback loop
Neural regulation
Other brain regions like limbic system and frontal lobe influence
hormone release
Experiential responses
You can learn to control release of hormones with experience
Experience alters structure and function of hypothalamic neurons
Oxytocin- released by PP best known for uterine contractions and
milk let down, but oxytocin released by "aw isn't it cute"
experiences
Biological rhythms of hormone levels
Vary greatly through the day
Organizational, activational, and permissive effects of hormones
Organizational- cause permanent change in structure of organ,
most clearly during development
Corticosterone kills off brain cells to sculpt brain to
environment (can be induced by stress)
Activational- acute effects from hormone, non permanent
Corticosterone decreases inflamation
Permissive- Hormone must be present in certain level for other
physiological processes to happen
Corticosterone must be present in certain levels for adrenal
gland to metabolize fat
Steroids and neurosteroids
Most hormones we talk about are peptides acting on cell surface
Steroids and neurosteroids are chemical structures that cross cell
membrane easily
Have receptors on cell surface and cell nucleus
Bind to receptors in nucleus to turn on or off genes
Can cause acute and long term changes
Progesterone and pregnanolone work to decrease anxiety
levels (working to synthesize pregnanolone)
DHEA from androgens in men and women related to sex
drive (testosterone etc)
LEARNING AND MEMORY
Learning
Relatively permanent, comes from experience
Neuroplasticity
NS must change to learn something, some kind of adaptation in neuron or
Test 2 notes Page 3
NS must change to learn something, some kind of adaptation in neuron or

biochemistry
Hebb Synapse
Father of neuroscience
Speculating on how NS works, when A acts on B repeatedly, something
changes to make A's action on B more efficient
Habituation
Aplysia Californica- sea snails to study learning
Relatively complex NS compared to other mollusks and
invertebrates
Habituation- non-associative learning, a response that gets smaller and
smaller after repeated weak stimulus
Ticking of clock, clothes on skin, etc
EPSP in motor neuron decreases with repeated stimulation thus much less
likely to have an action potential in motor neuron
Where is change? Calcium channel experiences change that inhibits
opening of calcium channels
Sensitization
Response to stimulus is strengthened with repeated presentations of
stimulus is stronger than normal
Interneuron makes axoaxonic connection to terminal of sensory neuron
No molecular change in Calcium channel, but still allowing more Ca in to
excite larger EPSP
Broader Action Potential caused by potassium flowing out (Spike
broadening)
Potassium channels become phosphorylated
Axoaxonic connection releases serotonin from interneuron to cause
second messenger cascade (metabotropic receptor) results in
phosphorylation
Associative Learning
Linking unrelated stimuli to elicit response
Long term potentiation LTP
Increase in synaptic efficiency
Seen in mammalian system
Changed size in EPSP lasts for long time
Studied by Bliss and Lomo
Took hippocampus and cut slices out of it
Hippocampus has very regular cellular organization and
connectivity
Stimulation results in increased EPSP amplitude for long term
Neurochemistry of LTP
AMPA is more simple ionotropic receptor, opens sodium channels in
response to glutamate
NMDA doubly gated with voltage and glutamate
Need two inputs, set up nicely for associative learning
Needs strong electrical stimulus to displace Mg, and needs weak
electrical stim from glutamate
Actions of Ca on postsynaptic neuron
More responsive of AMPA receptors to glutamate
Forms new AMPA receptors
Retrograde messengers trigger more glutamate release
Nitric oxide
Initiates increased production of NT
LTP works much better with two inputs synergizing together
Human brain works around 40Hz to facilitate LTP
Long Term Depression
Decrease in synaptic efficiency
Involves NMDA and calcium entering, but decreased responsiveness of AMPA
receptors and decreased numbers of AMPA receptors
LAST CLASS REVIEW

Describe habituation and molecular basis in sea slug
Describe sensitization
Molecular basis for LTP
Test 2 notes Page 4
Test 2 notes Page 5
Development and Developmental Disorders

Tuesday, October 01, 2013
1:27 PM
Homework:
Today's Topics:
Next paper due next Tuesday

2nd test two weeks
Important Points:
Paper is on website, measure of brain, electrical activity, etc, references
Lecture Topic:
During the lecture, take notes here. Insert a sub-page for each lecture topic.
Early Development
ADHD
Autism
Dyslexia
Summary
After the lecture, use this space to summarize the main points of this Lecture
Topic.
Test 2 notes Page 6
Early Development
1:29 PM
Development Defects
Teratology- monsters
Causes are varied
Stress, nutrition, radiation, disease, viruses,
Rule of thumb- changes in first trimester of human development are gross changes
Need lots of exposure to change things
Middle trimester is organ development
Third trimester is brain growth spurt
Alcohol is most harmful here
Early Stages
Conception
Zygote
Becomes hollow ball of cells that becomes blastula
Gastrula is hollow ball that sees cellular differentiation
Divisible into three layers, endoderm, mesoderm, ectoderm
Endoderm- inner layer becomes organs
Mesoderm- becomes muscles, fat, etc
Extoderm- thin cellular layer that becomes skin and skeleton, AND
NERVOUS SYSTEM
Neurula Stage
Neural plate forms, thickening of cells
Slowly neural plate curves in on self and fuses to form neural tube
Formed 25 days post conception
Initiated by retinoic acid and retinoid receptors
High levels of retinoic acid causes neural tube defects
Growth factors- acting on receptors facilitating formation of tube
Fibroblasts and transforming GF
Neural tube is about at midbrain area
Grows forward and back to form forebrain
Neural Tube defects
Anencephaly
Encephal- greek for brain (anencephal- no brain)
Failure of fusion from midbrain forward, still forms spinal cord
Invariably fatal
25% of fetuses are born alive, most are miscarried
Complete lack of functioning brain
Can be carried to term and be infant organ donors
Holoprosencephaly
Fully formed midbrain and part of forebrain, failure of fusion in cortical areas
Far more likely to live
Will always be institutionalized, severe seizures
No cortex, no real function
Spina bifida
Failure of fusion from midbrain backward along spinal cord
Degree of failure indicates severity
Relatively good prognosis
Can go in late term and surgically repair spinal cord
Will have abnormalities and retardation, degree can vary
Test 2 notes Page 7
Will have abnormalities and retardation, degree can vary

Highly related to malnutrition, often lack of folic acid
Prenatal vitamins help to prevent spina bifida
Some genetic basis, more prominent in Irish/British/Scottish descent
Development of the Embryo

Proliferation
Dividing cells, not an even rate
Different regions show different rate, dividing cells are all along ventricular surface, not
yet differentiated
Ventricular Zone
Notch signaling can result in larger or smaller number of cell divisions
Most cells are formed between two and four months post conception
Proliferation in Adult Brain
Still proliferation going on, particularly in hippocampus
Involved in learning and memory
Still not sure what exactly this is for
Increases with exercise, antidepressant medication, stress
Cells incorporate and make viable neurons and connections
Proliferation keeps going in olfactory bulbs as well
Uneven rate is what gives shape to brain
Have neural tube, start to see bumps along tube
Transverse subdivisions
Prosencephalon-forebrain
Mesencephalon- midbrain
Rhombencephalon- hindbrain
Specific patern of gene expression in each region
Forebrain divides into telencephalon and diencephalon
Forebrain divides from one bump to two (Telencephalon, diencephalon)
Hindbrain divides into metencephalon (pons and cerebellum) and
myelencephalon (Medulla)
Migration
Cells must move to their needed location
Cortex- radial glial cells form pathway for moving cells
Six layers, inside out organization
Chemical signaling in new neurons and radial glial cells
Extracellular matrix is chemical soup providing signals for neurons to travel along via
chemical attraction or repulsion
Migration problems create two common problems
Dyslexia
Specific reading disability
Brain cortex involved in actions is mixed up and scrambled in angular gyrus
Crossed wires and short circuits
Probably happens around six months post-conception
Schizophrenia
Pre-Frontal cortex development problems
Neurons dont get to where they should be, stuck in white matter not
making connections
Ectopic Neurons- out of place
Everyone has some ectopic neurons
Differentiation and Organization- ever increasing specialization
Stops moving, forms dendritic tree
Neurotransmitter type becomes differentiated
Test 2 notes Page 8
Neurotransmitter type becomes differentiated

Sex hormones start differentiating around six months (cyclic hormone release etc)
Cell Death- overproduction and weeding out
Most cells you will ever have at six months of development, then start dying off
Neural Darwinism
Use it or lose it phenomenon, if neurons start having action potentials and neurotrophic
factors they will be kept and used, if not they die
Apoptosis- cell death is different than caused by toxins
Caspases- involved in cell death and apoptosis process
Synaptogenesis
Cells have to stop at one point and grow axon to correct location
Nerve growth Cones
Very complicated structure "searches" for correct chemical signal in extracellular
matrix
Problems with differentiation and organization happen often in
Down's syndrome
Trisomy of 21st chromosome, frequent in young (-16) and older (40+) mothers
Mental retardation, distinctive physical defects, learning disabilities
Relatively shortened lifespans
Change in dendritic spines
Young start as long spindly spines, then to short stubby spines
DS children have fewer spines, and they remain long spindly
Short stubs are better electrical connectors
Phenylketonuria
Caused by recessive gene, hallmarks are retardation, self injury, psychotic symptoms
Phenylalanine --> tyrosine via phenylalanine hydroxylase
Tyrosine is precursor for dopamine and many NT's
With recessive gene you have malfunctioning PH enzyme
Causes buildup of phenylalanine and causes brain damage
Can be regulated with diet
REVIEW QUESTIONS
Describe the neurala stage
Neural plate is forming from ectoderm, fuses to form neural tube, starting at midbrain
and progressing forward and backward. Retonoic acid is needed to help form tube with
help from fibroblast and transforming growth factors
Complete by 25 days post conception
How does proliferation give rise to shape of brain
Proliferation and cell division happens at uneven rates so different portions of the brain
become larger. Forebrain becomes diencephelon, telencephelon, etc (know all divisions)
So much proliferation in forebrain that it must wrap around to form C shape
Migration in cortical cells
Radial glial cells form track for neuron to follow. Inside out organization
Two disorders with problems in migration
Dyslexia occurs in angulur junction
Schitzophrenia occurs in prefrontal cortex, some neurons remain stuck in white matter
Describe five things that happen in differentiation and organization
NT type determined
Synapses formed
Dendritic tree formed
Cell death
Steroids start working to determine sex
Compare contrast PKU and Downs
Test 2 notes Page 9
Compare contrast PKU and Downs

Downs trisomy, PKU is recessive gene
PKU causes breakdown of hydroxylase and sensitivity to phenylalanine
Downs causes physical defects and mental impairement
PKU causes retardation and psychotic symptoms
Test 2 notes Page 10
Fetal Alcohol Spectrum Disorders

1:46 PM
FASD caused by alcohol exposure

Leading known cause of mental retardation
Some genetic component, genetics of mother and fetus are implied in how severe effects of
alcohol are
Occurs mostly in third trimester when most differentiation is occuring
Symptoms
Mental retardation (sometimes not present)
Low probability of living independently
Huge proportion come into trouble with law
Does not mean they are violent, just social impairment, easily influenced by
people
Permanent, no cure to reverse alcohol effects. Can be prevented (in animals) but not
practical to implement
High risk of alcoholism later in adult hood
Greater than genetic risk
Occurs with other drugs as well
Epigenetic modifier
Myelination
Starts prenataly, doesnt finish till around 21 years old
Pre-natal starts in respiration, heart rate regulation, etc (medulla) then to primary sensory
areas, secondary areas, and finally prefrontal cortex
Some evidence that adolescent risk behavior is due to incomplete myelination in prefrontal
cortex
Can be delayed with under nutrition or malnutrition
ADHD
1:34 PM
Symptomes and prevalence

Impaired self regulation and impulsivity
Delay Discounting
Marshmallow test!
Learn to wait for reward and control themselves
People with ADHD have very difficult time waiting for reward
Tests of executive function
Looks at ability to organize and plan series of actions to solve problems
Time perception
ADHD shows extreme variability in how time is perceived
Grossly over-diagnosed, often misdiagnosed in people that are very intelligent
More prevalent in males, but over-diagnosed none the less
Comorbidity with anxiety disorders, bipolar disorders, addiction etc
Makes neural science very difficult
Genetic Risk
Endophenotypes, delay discounting
Separating by people with problems and those without
Dopamine D4 and D2 receptors, MAO-A and COMT
Enzymes that degrade catecholamines
Strongest genetic component for risk is genes involved in dopamine system
Genes that supress systems
Second leading genetic cause is noradrenergic system gene suppression
Genetic risk could in part be via passive interaction (parenting style)
Maternal Smoking
Increased risk independent of genetics and low birth rate
Nicotine has big affect on attention systems
Early childhood adversity
Nonspecific, moving a lot, chaotic family life, etc
Etiological heterogeneity and gene x environment interaction
Cause can vary greatly among individuals with same effect
Most people have a little bit of everything
Neurochemical bases of ADHD
Ridaline, adderal, pemoline, etc all stimulants that act to increase dopamine and
noradrenaline at synapse (agonist drugs)
Levels of MHPG in cerebrospinal fluid
Noradrenaline metabolite (breakdown product)
Observe lower than normal levels of MHPG
Indicates lower than normal levels of noradrenaline in ADHD brain
Imaging studies
Frontostriatal system findings
Prefrontal areas show hypo activation during inhibition tasks
Failure to activate prefrontal cortex, anterior cingulate, right caudate and left parietal
ADHD people cant bring those structures online as well
Subtle reduction in volume of frontal lobes, basal ganglia, and cerebellum
Suggests fewer synaptic connections, dendritic trees, etc
Mesocorticolimbic and frontostriatal pathways are neural circuits that then impair cognitive
function to manifest in behavioral symptoms
function to manifest in behavioral symptoms

Treatment
Medication
Stimulants
Help facilitate attention on objective tasks
Limited evidence that it helps adults with adhd
Less than 50% of adults show positive response
Only
work about 70% of the time for ALL people with ADHD
Risks
Heard defects are a high risk factor
Growth retardation
Long term effects
Controversial, rate of drug abuse in people taking stimulants for long term is
very high
From animal studies, young animals on stimulants show increased tendancy to
take that drug in adulthood, and show attention problems when removed from
the drug
Autism
Thursday, October 03, 2013
2:17 PM
Wide range on autistic spectrum, but most are more towards sever side
70% associated with brain damage
Asbergers is considered to be high functioning autism
7-1 male to female
Clinical autism closer to 4-1
Autism is considered to be present from birth
Early signs are indicated by shared gaze
Babies follow eyes of others to look where you look
Autistic infants do not track eyes and gaze
Autism differs from mental retardation in symptoms
Systemizing vs mind blindness
Lack of communication
Social aloofness, failure of empathy
Lack of reciprocal play behavior
Around 3-4 people truly begin to play with each other, then imaginative pretend play with
others begins
Autistic children do not exhibit reciprocal imaginary play
Autistic children prefer order and systemization
Mind blindness
Huge problems with theory of mind
People's minds are different than yours
People have different feelings than yours
Peekaboo- young kids (<2) cant understand that you can see something that
they can't
Sally-anne test
Prevalence
Increase in past several decades
Some conflict that there is over diagnosis vs real increase, fairly well studied that there is
real increase beyond genetic drift
Some highly prevalant "pockets" or geographic areas
Huge gender preference toward males (See above)
Genetics
Autism starts very early
Monozygotic (dischordant) vs dyzogotic studies
Many attempts to actually find genes, hundreds or thousands of genes involved,
heterogeneity with polygenic inheritance along with significant gene-gene and geneenvironment interactions
Genes targeted in autism
Chromatin remodeling and transcription
Bundle up DNA regulates epigenetic regualation
Actin cytoskeleton dynamics
How neurons are shaped
Synaptic scaffolding
Shape of synapse is affected
Neurotransmission and second messenger systems impaired
Apoptosis cell death is altered
Cell adhesion molecules
MANY are developmental and happen very early
MANY are developmental and happen very early

Genetic predispisition points to problems with cell migration
Transmission disturbances of excitatory inhibitory balance, and abnormal
synaptogenesis
High rates of autism in silicon valley
Looking for toxin in industry and parents with some autistic tendencies
Nonrandom mating could be implicated
Neural Changes
Cerebellum
Missing cells, missing large dendritic trees, and smaller than normal
Autism does not look like classical cerebellum damage
Cerebellum is very important in switching between modalities
Auditory, visual, somatosensory, etc
Orbitofrontal cortex and medial temporal areas (amygdala)
Not missing structures and not damaged, but missing activation (seen in scans)
Effects at birth are very low level, but needed to develop high level thinking
Dyslexia
1:34 PM
Developmental Dyslexia
Reading is impaired, cannot be explained with general learning deficit etc
Reading is very new evolutionarily
Only 35% of adults read above the level of a 14 year old
Angular Gyrus
Right at meeting of occipital temporal and parietal lobe
Dyslexia is more common im males, related to other learning disabilities, left handedness, and
immune function
Dyslexia and left handedness show higher rates of immune dysfunction
Testosterone theory by Geschwind
Planum temporale
Typically larger on left than on right
Dyslexics do not show this size differential
Testosterone prevents neuronal growth
Disrupts immune function
Testosterone exposure occurs too early in boys so it inhibits left side of PT,
results in higher probability of left handedness, etc etc
McCandliss and Noble
Dyslexics must "sound out" word letter by letter, some inability to look at word and see the
whole world
Superior temporal gyrus
Visual word form area, left side of STG shows activity, as people become expert
readers it shifts to Fusiform gyrus
Never able to show that elaboration and ability to automatically read
Interventions and effect on brain
If caught early you can help prevent
Phonetic training to discriminate different sounds
Shows greater activation and hopefully leap to fusiform gyrus
Genetics
Some evidence that genetics is implied
Magnocellular visual system and migration problems
Drugs and Addiction

A)
B)
C)
D)
E)
1:54 PM
Classes of drugs
Theories of Addiction
Neurobiology of addiction
Genetics of Addiction
What do genes for alcoholism code for?
Classes of drugs
1:55 PM
A) Drugs are classified by most prominent psychoactive effect

a. Antianxiety agents and sedative hypnotics
b. Antipsychotic
c. Antidepressants
d. Mood Stabilizers
e. Opioid analgesics
f. Psychomotor stimulants
g. Psychedelic and hallucinogen stimulants
B) Many drugs are discovered accidentally
C) Barbiturates
a. Produce sedation and sleep (eg alcohol)
b. Can cause general anesthesia, coma, and death
c. Rarely used now, other than as sedation before surgery
d. Popular in sixties
D) Benzodiazepines
a. Minor tranquilizers
i. Reduce anxiety (Valium)
ii. Often used for temporary purposes (e.g. coping with stress due to death in family)
E) Both barbiturates and benzodiazepines work on GABAa receptor
a. Excitation produces influx of Cl- which hyperpolarizes neuron
b. GABAa has two sites
i. Sedative hypnotic site- alcohol and barbiturates directly influence cl- influx
ii. Antianxiety site- Benzodiazepines, enhances binding effect of GABA
1) Effect is dependent on amount of GABA present
a) Harder to overdose
c. Debate about if barbiturates and benzodiazepines are addictive
i. Definitely habit forming
F) Antipsychotic agents
a. Major tranquilizers (Neuroleptic)
i. Drugs block D2 dopamine receptor
ii. Used for treating schizophrenia
iii. Mechanism of therapeutic action is still not understood
1) Immediate effect of reducing motor activity
2) After short period of use (3-5 weeks) there is reduction in symptoms of
schizophrenia
a) Particular reduction in hallucinations and delusions of schizophrenia
3) Negative side effect of dyskinesia- impaired control of movement
G) Antidepressants
a. Three Classes
i. Monoamine oxidase (MAO) inhibitors
1) Block enzyme MAO from degrading dopamine, noradrenaline, and serotonin
2) Good for treating depression with anxiety associated with it
ii. Tricyclic antidepressants
1) First generation antidepressants with a chemical structure characterized by
three rings that block serotonin and noradrenaline reuptake transporter
proteins
iii. Second generation antidepressants
1) Blocks reuptake of serotonin (SSRIs)
a) Selective serotonin reuptake inhibitors
a) Selective serotonin reuptake inhibitors

i) No effect on blood pressure, cause weight loss
iv. First and second generation antidepressants have side effects of decreased sex drive,
mood blunting, etc etc
b. Antidepressants affect synapse quickly, but it takes weeks for their antidepressive actions to
develop
c. Any antidepressants will increase neurogenesis in hippocampus
i. Mild depression often helped by exercise
d. 20% of patients with depression DONT respond to antidepressants, indicating many causes
H) Mood Stabilizers
a. Clas IV used to treat bipolar disorder
b. Mutes intensity of one pole of the disorder, making other pole less likely to recur
c. Mechanism not well understood
i. Lithium may increase serotonin release
ii. Valproate may stimulate gaba activity via effect on sodium channels
iii. Treatment compliance is difficult
I) Opioid analgesic
a. Drugs with sleep inducing (narcotic) and pain relieving analgesic properties
b. Opiates
i. Come from opium, opium poppy
c. Pure substances derived from poppy plant
i. Codeine: cough medicine and pain relievers
ii. Morphine- powerful pain reliever
1) Heroin is derived from morphine
a) Fat soluble and penetrates BBB faster than morphine, provides rapid pain
relief
d. Opiates are potentially addictive
i. Although addictive, not as harmful
e. Nalorphine and naloxone
i. Opiate antagonists that block effects of morphine
ii. Also used for treatment of addiction
J) Psychomotor stimulants
a. Increase motor behavior, elevate mood and alertness
b. Cocaine
i. Obtained from coca plant
ii. Blocks dopamine reuptake (agonist) more dopamine in synapse
iii. Used originally as topical local anesthetics
1) Derivatives like novocaine are common
iv. Not thought to be addictive originally
1) Withdrawl effects are psychological, dysphoria etc
2) Contrast with heroine withdraw is more physical (like flu)
c. Amphetamine
i. Double dopamine agonist, releases dopamine into synapse, blocks reuptake as well
ii. Stronger longer lasting effects, but feels like same drug as cocaine
iii. Uses
1) Asthma treatment
2) Study aid
3) Improve alertness and productivity
4) Weight loss aid
iv. High abuse potential
1) Methamphetamine enters brain faster, causes degeneration of neurons in
frontal cortex
d. General Stimulants
d. General Stimulants
i. General increase in metabolic activity of most cells
ii. Caffeine
1) Psychoactive
a) Inhibits enzyme that normally breaks down second messenger cyclic AMP
i) Gives you more energy
b) Increase in cAMP leads to increase in glucose production, more energy
available
2) Coffee and tea products account for more world wide trade than wine and
liquor, second only to food trade
K) Psychadelic drugs
a. Alter sensory perception and cognition, produce hallucinations
i. Four main types
1) Acetylcholine
2) Norepinephrine (Mescaline)
3) Serotonin (LSD, psilocybin)
4) THC (Marijuana)
a) Some debate if there is more involved as stimulant as well, distorts
perception but wont cause hallucination to degree of LSD
b) Potency has increased drastically
c) Addictive debate is still up in the air, believed to be about as addictive as
alcohol
Theories od Addiction
1:31 PM
A) Becomes a compulsion, reflexive use

a. "can't imagine living without it"
B) Addictive substances vary a lot in their subjective effects
a. Cocaine vs opiates vs alcohol vs caffeine etc
b. Subjective effects are NOT what makes things addictive, they might be implied
in continued use to develop addiction
C) Theory of Negative reinforcement
a. We will work to avoid something unpleasant
b. Idea was that addiction was result of avoiding withdraw
c. Problem with theory is that one of issues with addiction is long term relapse risk
D) Theory of positive reinforcement
a. We do addictive drugs because they make us feel good
b. Compulsive addicts need drug to feel normal, euphoric high goes away
relatively quickly
c. Some addicts go into paranoid episodes after long term use, and continue using
even without euphoria
E) Incentive sensitization theories
a. Idea that initially you take a drug out of curiosity etc, drug works in brain areas
involved in motivational behavior. Over time the drug sensitizes that system to
become something to drive motivation
b. Incentive value of drug becomes hyper active
c. Shift from liking the drug to needing the drug
d. Brain regions involved in addiction are same areas involved in thirst, hunger, sex
drive, maternal instinct, anything fundamentally motivated
F) Classical conditioning
a. Pavlovian processes
G) Neural models based on Koob and Bloom 1988
a. Find where things act and locate common regions
b. Particular system that all addictive drugs impact
c. Dopamine activity is directly or indirectly affect dopamine activity from VTA to
nucleus accumbens
i. Involved in all fundamental motivational process
ii. Addictive drugs hijack this system
d. Dopamine activity increases with unexpected reward or punishment
H) Understand the Koob and Bloom simplified process
a. Central and basolateral nuclei are involved highly in addictive cues
b. Prefrontal cortex involved in cortex
c. Ventral subiculum involved in context of addiction (favorite bar, friends, certain
coffee shops, time of day etc)
d. Brains homeostasis mechanism will inhibit dopamine mechanism
i. When off drugs the dopamine activity is very low
1) Dysphoric, not a lot of pleasure in anything
2) Takes a long time for dopamine mechanism to correct itself
I) Neurobiology of addiction, Goldstein 2009
a. Impaired insight, failure to seek treatment
b. Failure in circuits underlying interoception, self awareness, and socioemotional
cognitive responses
i. Addicts engage in hurtful behaviors towards family and friends but have
no concept of wrong doing while on drugs
no concept of wrong doing while on drugs

c. Results of goldstein
i. Role of insula and anterior cingulate cortices
1) People make discrimination decisions about stimuli
a) Make an error, ask if they were conscious of making error
2) Insula is right next to somatosensation areas for body
a) Important for how you feel
ii. Addict is missing subconscious cues that maybe this is a bad decision,
unaware that it may be a mistake
1) Shows little activation in insula and cingulate during decision
making
The Senses
1:14 PM
General Properties of Sensory Systems

Vision
Audition
Test Three Page 23
General Properties of Sensory Systems

1:29 PM
A) General properties
a. Visual, Auditory, Somatosensory, Gustatory, Olfactory
i. Gustatory and taste work together
ii. Most of the time we are working in a multi sensory environment
b. Receptors
i. Receptors for senses that transduce physical information into neural
information
1) Transduction
a) Light energy transformed into action potentials, sound
waves into neural energy
c. Thalamus
i. All senses except olfactory are processed through thalamus
1) Olfactory goes directly to cortex
2) From thalamus everything Is projected to cortex
a) Most things upon reaching cortex are crossed
b) Right senses to left brain, left senses to right brain
c) Cortex regions communicate with each other
d) Topographic Organization
i) Adjacent parts of the world are in adjacent parts of
cortex
ii) Amount of cortex devoted to particular piece of world
is dependent on sensitivity to that part of world
Very sensitive to speech region of frequencies
Little cortex devoted to peripheral vision, much
more devoted to direct field of vision
e) Columnar Organization
i) Vertically through six layers of cortex
ii) Group of cells in column of cortex share response
characteristics
Cells in column of visual cortex respond to same
aspect of world
Column of auditory cortex responds to same
frequency in that area
d. Parallel Pathways of information processing
i. Hierarchical processing is impossible with the speed that we must
process
ii. Parallel pathways process different aspects of the world simultaneously
1) Color in one area, movement in another, objects in a third, then
somehow unified into a subjective experience "Binding Problem"
e. Perception vs Reality
i. We dont really see reality, we see only what we perceive with our
senses
1) Snakes that see in infrared regions, birds with 4 cones instead of
three and see colors we cant imagine
Test Three Page 24
Vision
2:22 PM
A) Vision
a. Cell Layers in retina
i. Rods and cones connected to bipolar cells, connected to ganglion cells that project directly
to brain
1) Inside rods and cones are opsins (light sensitive chemical) that change their shape and
break down when exposed, alters ion channels in rods and cones to release NT to
bipolar --> Ganglion-->axon-->optic nerve--> brain
ii. Horizontal amacrine cells- lateral connections, inhibit and enhance different cell firings
iii. Rods- opsin that is extremely sensitive to light
iv. Cones- Opsins that break down with a particular wavelength
1) Three types
2) Color blindness usually caused by missing cone type
v. Cones have high acuity- for every cone there is one ganglion
vi. Rods have low acuity- rods combine (up to 100) to one ganglion
1) Combining information loses detail
b. Single Cell Recording
i. Implant a plate into brain where you can drop electrodes to puncture a single cell and
record its action potential
ii. Receptive field- the type of stimulation that results in maximal number of action potentials
or minimal action potentials
iii. Ganglion Cells: Drop electrode into cell, shine light around visual feed and find where
response is
1) Ganglions have center surround receptive field, with two types (on center and off
center cells)
a) Receptive fields overlap extensively
b) Thalamus has center surround receptive fields (larger)
iv. Slide 7 is path of vision
1) Primary visual cortex=striate cortex=V1
2) Superior colliculus
a) Orients before you actually know what you see
b) Reflexive and subcortical
c. Crossing of optic tracts
i. NOT Right eye/ left eye, it is right VISUAL FIELD and left VISUAL FIELD
1) Crossing dependent on what side of visual field
2) Nasal portions of retinas cross to opposite side
ii. Optic nerve comes to optic chiasm
1) Axons of ganglion cells make connections in lateral geniculate nucleus
a) Very distinct cell layers that process specific information
2) From LGN information is sent to and processed by V1 (primary visual cortex/striate
cortex)
3) All of these structures have venter surround receptive fields
iii. Cells in striate cortex
1) Simple Cells
a) Bar in a particular orientation in a particular place
2) Complex cells
a) Bar of light that move across circular receptive field at particular angle
3) Hypercomplex cells
a) Bar of light in particular orientation anywhere in the on part of receptive field
iv. Organization of striate cortex
Test Three Page 25
iv. Organization of striate cortex

1) All cells in column share orientation preference
2) Orientation bias shifts ~10deg for each adjacent column
3) Each cell in series of columns responds to same area of visual field
4) Ocular dominance- particular cell will respond primarily to left or right visual field
5) Hypercolumn- group of columns that contains all of the orientation biases, AND both
left and right occular dominance
v. Organization of cells in columns and blobs
vi. Ventral stream to temporal cortex
1) "What System"
2) Clearly involved in recognition of form, what are you seeing?
vii. Dorsal Stream to Parietal Cortex
1) "Where System"
2) Involved in localizing what you see and detecting movement/motion
viii. Dorsal/Ventral streams processed separately but in parallel
B) Disorders of visual cortex
a. Blindsight
i. Patients with damage to area V1, primary visual cortex
1) No subjective awareness of vision
2) Preserved ability to localize stimuli, detect movement, and perceive orientation of
lines or simple shapes
ii. Explanations
1) Small islands of intact visual cortex
2) Chimpanzee named Helen, surgically had cortex removed, and still showed blindsight
tendencies
3) Weiskrantz kept Helen as blind monkey pet, confirmed at death that she had PVC fully
removed
4) Blindsight due either to superior colliculus OR extrastriate projections from thalamus
a) Unconscious vision without visual cortex, still no subjective experience
b. Visual Agnosia
i. Damage to temporal cortex (what system)
1) Bilateral, usually from CO poisining
ii. People lose ability to recognize objects
1) They can still see and have good motor acuity and detection
2) Have no idea WHAT they are seeing (knowledge of world does not meet up with their
sensory input
3) No recognition of food, very serious
4) Prosopagnosia- cannot recognize faces
c. Balint's Syndrome
i. "where pathway" impairment
ii. Damage to parietal lobe from primary cortex (dorsal stream)
iii. Individuals know what they are seeing, but have difficulty with visually guided movements
i.e. reaching for an object
d. Visual hallucinations, visual experiences
i. With drugs, disorders, etc. All are due to brain activity and are "real"
e. McGurk Effect
i. Cross sensory illusion
ii. When listening to someone talk you also watch their mouth
iii. Perception of speech influences what you hear
Test Three Page 26
Audition
1:53 PM
C) Audition
a. Sound waves themselves are "sound" compressed or ucompressed air
i. Frequency=pitch
ii. Amplitude= loudness
iii. Complexity= timbre
b. Auditory receptors are hair cells
i. Moves eardrum-->bones-->fluid etc etc
ii. Invferior colliculus first to process auditory input
1) Damage causes poor orientation to sound
iii. Medial geniculate nucleus of thalamus has projections from inferior colliculus
c. Primary Auditory Cortex
i. Heschl's Gyrus(considerably inside lateral fissure)
ii. Wernicke's area in left posterior temporal cortex involved in comprehension of speech
iii. Broca's area in frontal left cortex
1) Involved in speech production
iv. Posterior parietal cortex for localizing and guiding movement by sound (Where cortex)
d. Speech
i. Production and comprehension
ii. Both of the aphasia's are due to left side brain damage
iii. Broca's aphasia- trouble producing speech, but still good comprehension. Aware of
deficit, generally frustrated by inability to produce speech
1) Comprehension is poor in scenarios when the grammar of speech conveys
meaning
iv. Wernicke's aphasia
1) Have affluent aphasia, speak a lot, but speech is meaningless
2) Do not understand much of any speech
3) Individuals are unaware of impairment
v. Broca's aphasia rehabilitation
1) Teach people to sing, very effective
2) Musicality of speech conveys lots of meaning (right hemisphere function)
3) Trains right hemisphere to take over function that is lost from left hemisphere
damage
Test Three Page 27
Motor System
2:18 PM
Basics
A) All movement is constantly adapted
B) Kinesthetic sense
a. Knowledge to move appropriately and adapt constantly
b. Knowing how body is moving I space
c. Extrafusal muscle fiber
i. Big muscle fibers that contract and relax, are enervated by alpha
motor neurons
d. Sensory systems of muscle systems
i. Muscle spindle organ
1) In all muscles are small muscle fibers that are in parallel
(interfusal muscle fibers)
a) Are sensory, do not do any movement (sense what
other muscle is doing)
b) Receive axon from gamma motor neuron
2) Has sensory fibers that detect stretch, directly connected to
alpha motor neuron
ii. Golgi Tendon Organ
1) Stretch receptor in tendons, controls how much force your
muscles must exert to keep muscles where they are
supposed to be
2) Has inhibitory interneuron
a) Inhibits alpha motor neuron so that muscles relax
b) If you over exert your muscles they will be totally
inhibited and completely relax
i) Power lifters example (cheating system by
anesthetizing golgi tendon organ so that relaxing
reflex is lost)
C) Pyramidal system
a. From motor cortex down lateral and ventral corticospinal tracts (slide 3)
b. Lateral corticospinal tract controls limbs and digits
c. Ventral CS Tract controls trunk, posture
i. Cut spinal cord, lose all voluntary movement below cut
d. Damage to Pyramidal system manifests itself in pyramidal signs
i. Lose control of outer extremities
ii. Postural control stays intact
iii. Flaccid paralysis initially- muscles lose all tone, over time a spastic
paralysis can develop (rigid). Eventually recovery is possible
iv. Lack of motor response to somatosensory input
D) Extrapyramidal system
a. Basal ganglia including caudate and putamen (striatum), globus pallidus
(internal and external)
b. Substantia nigra projects to basal ganglia
c. Subthalmic nucleus also projects to basal ganglia
d. ^^ Controls voluntary and especially trunk movement
i. Damage causes lots of involuntary movement
E) Slide 6 for process of movement
Huntingtons Disease
Parkinsons Disease
Test Three Page 28
Huntingtons Disease
Parkinsons Disease
Dominant gene with
Shakes and tremors, clumsiness,
50% inheritance
Adult onset disease ~60
Initial symptoms of
Devolves into lack of voluntary
fidgeting, devolves into
movement, most people wheelchair
arms and legs
bound
Cognitive blunting, haze over their
involuntary movement
Full fledged limb flinging
mind
around
Emotional blunting
Metabolism is huge
Can be drug induced
problem, constant
Designer drug in california
caused rash outbreak of early
motion burns lots of
onset severe parkinsons
energy, causes people
Loss of dopamine fibers from
to lose lots of weight
Often misdiagnosed as
Substantia Nigra to Basal ganglia
F)
schitzophrenia
Disease is clinically silent until
Begins in adulthood, ~
~80% of neurons are
40-50
destroyed
Typically will die within
Upregulation of dopamine
10 years
receptors as you start to lose
Gross atrophy of the
neurons, brain compensates
basal ganglia
for degeneration
Eventually the brain can
So much
shrinkage and cell
not keep up
loss that the
structure
collapses
a. Prevalence of different symptoms depends on corticostriatal loops

affected
b. Huntingtons caused by dominant gene on chromosome 4, codes for
huntingtons protein
i. Gene is trinucleotide repeat, different individuals have so many
repeats, 24-56, huntington's shows excessive trinucleotide repeats
1) Number of repeats can indicate when it will start
2) If gene is from father the repeats will increase, and generally
show worse prognosis
c. Changes in the direct pathway in parkinsons (damage to substantia nigra
inputs)
d. Changes in indirect pathway in huntingtons (damage to
caudate/putamen)
i. Direct and indirect pathways slide 7
ii. Dopamine effects can be excitatory or inhibitory
Test Three Page 29
Emotion and Motivation

Tuesday, November 05, 2013
Final Monday dec 9th
1:15 PM
Sexual Behavior
Androgen insensitivity syndrome
No testosterone receptors but XY Chromosomes, effectively female
Androgenital syndrome
XX Chromosomes
Females produce testosterone through adrenal glands
In this condition adrenal glands over produce testosterone too early
Results in more masculinized appearance
Clitoris becomes enlarged to resemble penis
Internal organs are female
Later onset, third trimester
Recognized at birth
Adrenal gland malfunction can be corrected early
Individuals who grow up this way are female, and have gender identity
strongly oriented toward female
Sexual orientation is more tended towards homosexuality
Gender identity does not have to do solely with testosterone or chromosomes
Identical twin case study
Twin baby boys born, around 6 months of age boys are circumcised
One baby has penis accidentally burnt off during laser circumcision
Decided to raise baby as girl, surgically altered sex change operation
Baby girl now exhibits "girly" behavior
Argument for gender identity being linked to socialization and how girls
and boys are treated differently
Around puberty girl struggles with depression and difficult social experiences
with peers
At age 14 girl is told whole story, tries to commit suicide
Age 21, has sex change operation back to male
Commits suicide age 38
Becomes relatively clear that gender identity is NOT just linked to socialization
but has deeper roots
There are unquestionably individuals with true gender identity issues, different than
sexual orientation, and different than cross dressing
Sexual Motivation
In Rats: Motivation (how strong you will work to find partner, how rewarding it is) vs
Performance (actual sexual act)
Motivation is based in amygdala
Males will work for female rats, opioids wipe out motivation
Female rats will not work to access one male, but will work for 5-6 males
Hypothalamus involved in performance
Both male and female performances seen with hypothalamus
stimulation and in play behavior
Hormones
Female rats and mammals must be in certain hormonal state to be
receptive to sexual behavior
Contrasts very strikingly with humans, humans DO NOT exhibit
correlation between sexual receptivity and hormonal state
Males- testosterone is not activational for sexual behavior
Testosterone is permissive, must have certain level for motivation
to be intact
In Humans
Performance vs motivation
Must have certain levels of testosterone in men and women to have typical
level of sexual motivation
Estrogen and progesterone do not impact sexual motivation in women, but
damage to adrenal glands in women will show decreased motivation
Men will have diminishing motivation as they age and produce less
testosterone
Huge effort on part of drug companies to develop drug to increase sex drive in
women
Particularly after women can no longer have children
Temporal Lobe cortex highly involved in motivation in humans
Epilipsy in Temporal lobe (hyper activity) have decreased sex drive,
controlling epilepsy shows increased sex drive
Amygdala could be output pathway but temporal lobe does modulation
Sexual Behavior
Sexual Orientation
Sex related differences in hypothalamus
Lavai Compared het females, het males
Preoptic area contains twice as many neurons
Bed nucleus of the stria terminalis is 2.5 times larger
NAH3 region is 2 times larger
Suprachiasmic nucleus contains twice as many neurons
Hypothalamus of homosexual males differs, is inbetween hetero males
Test Three Page 30
Gender difference in sexual orientation spectrum

Men show bimodal distribution toward either end
Women do not show bimodal distribution
More likely to be within bisexual realm
Hypothalamus of homosexual males differs, is inbetween hetero males

and hetero females
"Third sex" hyphothesis
Issues with study
Most homosexual men died from AIDS, which affects brain
Good correlations, but no causal evidence
Causal arrow can go either way, but news media does
not report those things
Genetic basis
Hamer and Colleagues 1993
Sample of 114 homosexual males (at extreme end of
homosexuality)
Higher than average incidence of male homosexuality on
maternal side of mens families, but not on paternal side
Potential involvement of x chromosome, certain region on x
chromosome shared between individuals in family that are
homosexual
HOWEVER genes specify proteins, not sexual behavior
Little followup on any study because difficult to get funding
Believed to be genetic predisposition, but likely many ways to get to sexual
orientation
Sexual orientation predates puberty
Best predictor of male homosexuality is early age play behavior (4 to 5 years
old)
Individuals show gender preferences way before thinking about sex
Individuals have flexibility with gender preferences
Social behavior
Affiliation as a drive
Humans need social bonds, without them you become depressed
If isolated, people feel strong drive to have human contact
People with lots of friends tend to have weak bonds
People with few friends tend to have very intense bonds
Evolution of complex social groups
Intelligence of human beings developed from the complex social groups
Children solve problems better in a social context
Social behavior in primates
Effect of lesions of orbital frontal cortex or amygdala
Has heavy reciprocal projections
Damage to either region shows decreased social behavior, loss of
dominance, inappropriate behavior, change in social preference, loss of
facial expression, and social vocalization
These are the types of damage that will change who you are
Variability of effects
Changes in cognition seen
Phineas Gage
Rail road worker, hardworking family man, good employee
Dynamite accident, has tamping rod through orbit of eye and skull
Lives, has strong change in personality, almost complete 180 turn
Pseudodepression and pseudopsychopathy
Group work
Relatively recent development that people live in groups larger than 100
Stereotypes
In group
Group we think we belong to
Out group
People who we think are not part of our group
^^Can Change routinely and quickly, in different scenarios
Illusory correlation
Out group is all the same, in group differs
Îllusion of out group homogeneity accompanies in group
differentiation
^^^Can lead to discrimination against out group
Brain wants to categorize things into sets
Categorization used as a heuristic, as a trick, to handle large amts of
information
Categorization is basic property og brain
Modeling in olfactory cortex
Three synapses, LTP individual and categories
Wiring is set up to put odors into categories
Honey Bees
Categorize automatically different odors with different
dances
Long term potentiation and properties in neural networks
Issue is using categorization too rigidly, ends with racism and
discrimination
Categorizing people on NON-CONCRETE things is natural and beneficial (ie
kind/mean, friends/enemy)
Categorizing people on CONCRETE things is dangerous (Skin color, gender, etc)
Harris and Fiske 2006
Steryotype content model (steryotypes of different individual)
Stereotype and take great pride in that stereotype (All USC Fans are
great fans and people)
All multimillionaires are ruthless businessmen and have tons of
money (Envy)
Test Three Page 31
money (Envy)
Pity (feel sorry for particular group, elderly people are confused)
Disgust (Homeless people, etc)
Warmth and competence perception is also associated with stereotypes
When people think of other people under brain scan:
Ventromedial prefrontal cortex shows activation
When we feel disgust for a person it is de-humanizing for extreme
outgroup, and there is no activation of MPFC (medial prefrontal
cortex)
UnderGrad imaging @ Princeton
Subtraction from fixation
Run through many stereotypes and rank pride, envy, pity,
disgust, compassion, competence etc
Some groups (elderly and drug addicts) show high
levels of pity and disgust
Shows activation in insula and amygdala- (gut, visceral
feeling)(disgust)
Emotional deficits and moral cognition
Some groups where individuals are treated as objects and non human
Psychopaths have very little compassion and warmth for any other
humans
Lesions of ventromedil prefrontal cortex in childhood vs adulthood
Childhood damage impairs morality and human perspective
Adult damage DOES NOT impair moral cognition
Mood and Anxiety disorders

Depression
Abnormal regulation of feelings of sadness and happiness
Cause unknown, there is genetic component
Biological abnormality
About 70% of depressed people respond to antidepressants, most
increase levels of noradrenaline and serotonin
Limbic and prefrontal regions may be involved
Corticostriatal loops involved with emotion
Two sets, one for emotion and one for behavior
Limbic-thalamocortical loops involve insula (feeling of
illness, "can't move")
Depressed individuals act as sick individuals, like
having flu
Meloncholy depression more common- sleep a lot, not
active, etc
Agitated depression can inhibit sleep, very anxious
Anxious depression is increasing in younger
generations
WHO ranks depression as 3rd most dangerous disease
Change in sleep pattern is diagnostic tool
Some believe that depression is the greatest disease that plagues mankind
today
Deep and thorough inability to find happiness or regulate moods.
Inability to function
Some individuals are more prone to depression than others, but largely
unexplained
Repeated bouts of diagnosable depression have stronger genetic component
20% of adults will display diagnosable depression at some point, most with
repeated bouts
3x more common in women than in men
Women more likely to have FIRST episode, after first men and
women have similar stats in repeated difficulty
First episode of depression often during adolescence, women
perceive adolescent stress as much bigger deal
Efficacy of psychotherapy for depression
Psychotherapy has been shown to be just as effective as drug therapy,
and has better long term prospects
People learn to develop skills to control chronic depression
Mild to moderate depression is best cured with exercise
Efficacy of pharmacotherapy
Attempts to match pharmacotherapy with different depression subtypes
Tricyclic antidepressands (noradrenaline and serotonin agonists, block
reuptake)
More effective than SSRIs for serious depression, but causes
hypertension
SSRI (Serotonin agonist, new generation)
Usually first perscribed, dont cause weight gain, dont cause
blood pressure problems, but can inhibit sex drive and digestion
MAO Inhibitors (Inhibits enzyme that breaks down dopamine serotonin
and noradrenaline, agonist for all three)
Not a treatment of choice, except they are very effective for
individuals with anxious depression
Have lethal interactions with certain food types (anything
fermented, any antihistamines)
Electroconvulsive therapy
ECT- cause seizures in individual by running current through brain
(intended to cure schizophrenia)
Did not cure schizophrenia but it did alleviate depression
Test Three Page 32
Did not cure schizophrenia but it did alleviate depression

dramatically and immediately
Issues with ECT, we do not understand it at all, also causes
memory deficits
ALL Drug TREATMENTS INCREASE NEUROGENESIS OF HIPPOCAMPUS
Obsessive compulsive disorder
Symptoms
Obsessive thoughts
Compulsions are actual actions, ie germs, constantly washing hands
Striking feature is that individuals have a lot of insight into how
abnormal their thoughts and behavior are
Many people with OCD are also depressed because they have no control
but know they are abnormal
Some evidence that animals show OCD type actions
Particularly in overbred and pure bred strains of animals
Brain Imaging
Overactivity in orbital frontal cortex
So active that it is thinking same thought over and over
Caudate Nucleus
Involved in any kind of habitual movement
Compulsions become this ingrained habit that cant be controlled
Lesions and disorders that cause secondary OCD
Damage to globus pallidus (output from basal ganglia) and adult damage
to Ventromedial prefrontal cortex
Parkinsons, huntingtons, tourettes, chronic motor tic disorder, all
related to each other
Again activation of cortico-striatal-pallidal-thalamic loops
Treated with SSRI's
Not perfect, but does seem to help
Psychotherapy works fairly well
PTSD
Lots of attention, huge rate of increase as people return from war after
surviving serious trauma
Classical conditioning
Response is specific to cues
Can enter full flight anxiety response, cascades into agoraphobia,
nightmares, emotional shutdown,
One issue is that not everyone who undergoes traumatic stress has PTSD
Some genetic predisposition, those with PTSD are very easy to classically
condition
Unconscious style of learning
Imaging findings
Trigger PTSD stresses
Activation in
Anterior cingulate cortex
Orbitofrontal cortex
Strong emotion occuring
Brocas area
Not clear why activated, suggested that the
individuals are talking themselves through the
experience
Amygdala
Very involved in conditioned emotional responses
Differences in conditionability, personality factors, sensitization, autonomic
responsivity, and hypothalamic pituitary axis
Test Three Page 33
Circadian rhythms and sleep wake cycle

Thursday, November 07, 2013
2:18 PM
Circadian rhythms
Everyone sleeps, all animals (down to fish)
ALL animals have circadian rhythms
Refers to rhythm that is not caused by outside stimulation
Endogonous rhythm
Entrainment (setting rhythms to the world)- zeitgebers (anything that helps to regulate rhythms)
Sunlight, temperature, activity levels
Limits of entrainment- can you break the 24 hour cycle and move to 28, 36, 48 etc
Natural endogenous rhythm is about 25 hours, causes drift of cycles
You can get people to live a 24-+ 3 hour day by controling zeitgebers
Rhythms past that point become random and noisy
Suprachiasmatic nucleus (in hypothalamus above optic chiasm)
Major endogenous clock in nervous system
Very small nucleus, 10,000 neurons
Neurons are very tiny, not much cytoplasm, packed densely
Larger abundance of dendo-dendritic synapses
Could be inherent in endogenous rhythm, does not need ANY other input to
have electrical rhythm
Very difficult to disrupt circadian rhythm, even in deep comas or other stresses
One way to disrupt rhythm is to disrupt protein synthesis
Lesions (bilateral) of SCN
Destroys rhythm even with distinct zeitgebers
Loss of circadian rhythm in temp regulation, other brain regions, hormone levels, etc
Bilateral lesions wipe out most circadian rhythms
Two separate groups of Circadian Neurons
M-cells
Become active in morning, entrained by light (can shift activity with exposure
to light)
E-cells
Control evening activity and need darkness for entrainment
Individual differences may explain morning people vs evening people
Sleep and Wakefulness

REM Sleep
Slow Wave Sleep/NREM Sleep (night terrors (children often, usually are completely absent)and
sleep walking)
"Shifting modes of consciousness" lots going on while we sleep
Awake- EEG is small amplitude and constand rapid movement
Stage 1- dozy area, irregular small amplitude
As you fall asleep you get much larger amplitudes and regular rhythms
REM sleep is low amplitude and EEG looks like wakefulness
Over the course of an 8hr sleep cycle REM stages get larger and larger
Each sleep cycle is about 90 minutes
Alcohol and sleeping pills suppress rem sleep cycles
REM Rebound- if not enough time spent in REM cycles, REM becomes more dominant
Sleep Deprivation
As soon as you go to sleep you go straight to REM sleep
REM Sleep increases with studying and learning, intensive work
Over the course of development
Sleep less as you get older
Less REM Sleep as you age
Less likely to sleep as deeply (No stage 4 deep sleep) as you get older
Large herbivores spend little time asleep, have to eat more, small and noctournal animals sleep
more
REM Sleep
No muscle tone, lose all stretch
Deep deep inhibition, If woken during REM Sleep people report dream, story, illogical or
bizarre
More detail on EEG changes
See PPT Slide
Slow spindle waves in NREM Sleep, 12-14 hz and delta waves, 1-4 hz
REM sleep gamma waves 30-70hz and PGO spikes
Brain regions involved
Involves diffuse neurotransmitter systems
Locus Ceruleus
In Pons, projects noradrenaline forward and backward
Raphe Nuclei
Serotonin
Acetylcholine
Brainstem nuclei
Three systems work together to modulate cycle
Post-test Three Final Page 34
Eve Martyr- neural circuit that controls stomach of crab
FINAL MONDAY DECEMBER 9th 12:30
Three systems work together to modulate cycle

Hobson et al-2005
Waking
High levels of noradrenaline and serotonin, low acetylcholine
Noradrenaline and serotonin inhibit REM Sleep
Rem Sleep- Low Noradrenaline and serotonin, high activity of acetycholine
NREM- middle ranges of activity in all three
Brain Activity in REM Sleep
Decreased activity in dorsolateral prefrontal cortex
Involved in learning
Also decreased activity in striate cortex (No response to external stimuli)
Increased acctivity in limbic, paralimbic, cingulate, hypothalamus, amygdala, etc
Emotional areas are active
Extrastriate cortex and basal ganglia activated
Visual areas and voluntary motor activity
Why do we sleep and dream?
Sleep deprivation study
World record is over 10 days awake (15 year old boy)
No psychotic break, waxing and waning in attentiveness, little tolerance for
things that are boring
Was relatively active, played a lot of video games, showed little motor
coordination problems
No real issues, decreased attention span but not much else, recovers quickly
POW camps use sleep deprivation, becomes much more harmful under stressful
situations
Fatal Familial Insomnia (extremely rare dominant mutation)
Prions- abnormally folded proteins, causes mad cow disease and FFI, assumed to be
involved in Alzheimer's and Parkinson's
Damages thalamus by accumulating prions, causes degeneration of neurons
Permanent state of almost sleep
When unable to regulate sleep people die within 9 months
Not clear if death is due to more brain degeneration or if it is due to sleep
deprivation
Memory consolidation studies
Electrical activity during NREM Sleep mimics that in maze learning in rats
Very distinct pattern re-occurs in maze and in slow wave sleep
Sleep is needed to consolidate memories and discard unnecessary memories
More contemplative people spend more time in rem sleep
Humans form stronger memories while sleeping, training before bed leads to better
performance upon waking
Brains are extremely active during sleep, forming new memories, deleting
unimportant ones
PTSD and depression
Show huge levels of sleep problems, disrupted circadian rhythms
Sleep Disorders
Insomnia
Almost always related to stress
Can be related to drinking alcohol, elevation changes, etc
Most common sleep disorder
One of the most common causes of insomnia is sleeping pills and REM rebound
Sleeping pills are GABA effectors, inhibitory, but inhibits WHOLE brain, inhibits
REM sleep.
Destroys classic sleep pattern, only slow wave.
Wake up feeling groggy, etc
Long term use of sleeping pills (even just a week) causes withdraw,
causes REM rebound
Dream so much that you wake up, feels like you cant sleep so you
go back to taking pills again
Creates addict type pattern
Narcolepsy
Strongly genetic
Runs in families, 2% in japan, more strongly in Asian populations but not exculsive
Sleep Attacks
Usually occur when things are boring, person falls into deep sleep for 3-5
minutes
Cataplexy
Under high arousal situations people lose all muscle tone but not
consciousness
Still awake, aware they have fallen
Sleep Paralysis
Rather common, occurs when falling asleep or waking up
Not asleep, but you cannot move
Can be very terrifying and stressful
Hypnagogic hallucinations
People are awake, but slip into dream state
Dream state melds with awake state
Extremely confusing, people think they are losing contact with reality
Extremely confusing, people think they are losing contact with reality
High rate of suicide and depression in narcoleptic individuals
Doberman pinschers and Labrador retreivers have high levels of narcolepsy
Feinting goats
Sleep at night is very disrupted, most symptoms are REM sleep linked
Generally narcoleptics cannot drive
Treatment
Stimulants
Amphetamine, ritalin, etc
At night often take SSRI's or Tricyclic antidepressants
Helps to regulate REM sleep
Learning and Memory

1:55 PM
Point of having a brain is to learn and adapt to environment

Famous Case of HM
Most well studied case
HM was young man with serious temporal lobe epilepsy, bilateral, and not drug controlled
30 seizures per day
In late 60s had tissue causing seizures removed
Scoville was surgeon that performed procedure. (previously performed surgery on psychotic patients
with little effect)
Hippocampus, amygdala, and temporal lobe cortex removed bilaterally from HM
Side effect of HM
HM exhibited anterograde amnesia
Unable to form any new memories, but good idea of past memories
Zero short term memory, tested by Brenda Milner of McGill
HM had normal IQ and was not impaired after surgery
Good conversationalist as long as things werent too long winded
Could not form explicit memory, conscious memory
Implicit memory left intact
Ex. Mirror drawing practice (no memory of performing task, but gets better at task as he
practices indicating unconscious "muscle" memory)
Emotional blunting from loss of amygdala
Never upset about loss of memory
RB was in for cardiac surgery, briefly deprived of oxygen, showed complete anterograde amnesia,
brain showed same damage as hm
Clive Wearing
Explicit memory destroyed, implicit memory intact
Caused by viral encephalitis
Temporal lobe severely damaged, along with hippocampus and frontal lobe
More serious case of anterograde amnesia than HM, old memories more impaired
Still remembered his wife, and musical ability
Also had severe retrograde memory loss (forebrain, loss of old memories)
Boswell
Damage to medial temporal regions and orbital frontal cortex, and insular cortex
Both anterograde and retrograde amnesia for explicit memory
Implicit memory is intact, emotional memory is intact
Could show motor learning, and emotional learning
Two sets of caregivers, one treats Boswell very well, the others are cold and removed
After time show Boswell pictures of caretakers, and have him sort them by who he thinks he
would be friends with and who he wouldnt
Clearly defined emotional memory even though it is totally unconscious
Multiple Memory Systems

Explicit Memory
Autobiographical memory, memory of your life
Declarative memory, memory you can tell a story about
Semantic memory, sheer knowledge
Spelling
Implicit memory
Cannot tell story about, dont know that you know
Procedural memory, motor memory
"riding a bike"
Emotional memory
Emotional reactions
Triggered by visual stimuli, phrases, smells/scents,
Often when you have emotional memory you can extract out a declarative memory
Classical Conditioning
Part of memory system, emotional memory can be tied into classical conditioning
Operant Conditioning
Drugs of addiction, rewarding. VTA Accumbens system associatiation
Separate neural circuitry but with overlap
Memory is distributed across many parts of brain
Memory is NOT an all or none system
Ascending diffuse systems on different sectors and function of prefrontal cortex
From brainstem, ascending to other areas
From VTA, Locus coeruleus, dorsal raphe (dopamine, norepinephrine, serotonin)
Spatial memory and on line working memory coincide, overlap in prefrontal cortex and involve VTA
Dopamine system and norepinephrine system
Reinforcement learning and reversal learning/extinction
From VTA and dorsal raphe (dopamine and serotonin systems)
Reward system, delay discounting
Attention set shifting, SSRT, Response inhibition, updating working memory
Work in Norepinephrine system from locus coeruleus
Pulling in new memories to working memory, very dynamic system
Learning and memory, decision making Page 37
Anterograde amnesia- difficulty forming new memories
Explicit memory
Know flowchart
Frontal cortex and temporal lobe structures involved
When trying to form new memory it starts in temporal lobe
Eventual storage of memory is in prefrontal cortex
Temporal for new memories
Prefrontal for old memories
LTP in hippocampus is involved in formation of memory
As memory is stored it becomes more permanent
A single memory can be moved around as it develops and ages to different structures
Alzheimer's seems to degrade hippocampus first, then extends into prefrontal cortex
Oldest memories seem to stay intact
Implicit Memory
Particularly procedural memory:
Involve motor systems, Substantia nigra to basal ganglia
Basal ganglia are often habit memories, motor memories
Bypasses prefrontal cortex, seem to conflict and not work well together
Emotional memories
Subcortical
Amygdala (key in negative emotional memories) Works with Hypothalamus and Periaqueductal Grey (PAG)
Amygdala and Hypothalamus work with striatum (Reward, good or bad) and medial temporal cortex to give
context to things
PAG involved in species-typical emotional expression
Six base emotions for humans
Happy sad disgust anger fear surprise
Stimulate hypothalamus and you get undirected rage emotion
Damage to amygdala can show emotional blunting, seizures in amygdala can cause rage and attacks
Summary
Multiple systems work together
Prefrontal cortex involved in explicit memory
Working memory, problem solving, very conscious
Basal ganglia involved in implicit memory, motor learning, and habits
OCD, increased activation in caudate, obsessive thinking that isnt under conscious control
Amygdala and hypothalamus in emotional memory
All areas of cortex are involved in memory to some degree
Binding problem, how do our unified memories include so many pieces that are processed in different places
Decision Making
Thursday, November 21, 2013
1:54 PM
Levels of analysis for decision making

Level of implementation- how brain mediates decision making
Level of algorithm and representation- how do we actually make decisions, what are the inputs, what
are outputs
Task analysis- why do we make decisions, do we make decisions to maximize benefits, how do
populations work
Approach from a neuroscience point of view
Animal studies
Animals make choices all the time
Human
Studies
Tranel, Bechara, and Damasio, 2000, bechara et al., 2005

Critiqued by dunn, dalgleish, and lawrence, 2006
Iowa Gambling task
Normal people brought in with 4 decks of cards, and they will gamble
Pick up cards from each of 4 decks, arousal measured with galvanic skin sensor
Gambling for money, have probability of big reward, or big punishment from two decks
Other 2 decks have small rewards, small losses
Clearly the better choice
Typical individual in early stages has no idea what is going on, no galvanic skin response
As time goes on and they reach for punishment decks the arousal system kicks in
Eventually the subjects figure out the rig and show the proper behavior
Dividing tasks up into knowldege periods: pre-punishment, pre-hunch, hunch, conceptual
Anticipatory SCRs (skin conductance response)
Indicates that people make decisions via subconscious mechanisms
Some evidence that people will make a decision, then pro con to make their decision
make sense
Prefrontal damage causes people to NOT show anticipatory galvanic responses
Never show "this might be bad" response
Can even get to conceptual knowledge of task, linked to very poor decision making
Damaged individuals missing subcortical arousal that guides decision making
Somatic marker hypothesis
Prefrontal cortex has to be guided by somatosensory system, feeling that something is wrong
Intuition, etc
Somatosensory maps in cortex and insula, talk about how loops are activated
Classes of complex stimuli activate body loop or as-if-body loop
Activation constrains reasoning and decision making, marks outcomes good and bad
Activation can facilitate attention and memory, can influence decision making indirectly
Effects of bilateral amygdala lesions
Shows bad decision making
Damage to sensory systems involved with gut or internal feelings impairs performance in
decision making
Effects of peripheral neuropathy
Can show impaired decision making by not sensing body having high arousal
Effects of right ventromedial prefrontal lesions
REALLY causes people to make poor decisions
Act inappropriately in social settings, managing money, etc etc
Addiction impairs prefrontal areas
Decision making and emotion
Old literature focuses on rational decisions, pro con, risk reward etc
Old literature focuses on rational decisions, pro con, risk reward etc
New literature argues more for emotional decision making
Delgado and Dickerson 2012
Neuroeconomics approach
Melding cognitive and computational neuroscience grounded in classical learning theory
To understand econ you have to understand human decision making across aggregate populations
Decision making as function of trial and error reward learning, the corticostriatal system (cortex basal
ganglia habits etc)
Consumers do not change habits easily
Long term memories play huge role from medial temporal lobe system
Experiences impact what you learn to do by habit
Corticostriatal loops
Talked about with addiction
First VTA to Nuc. Accumbens as trial and learning
Then becomes motor habit
Dopamine and unexpected reward
Parkinson's disease patients on or off medication
Show less flexibility in decision making without medication
When medicated with LDOPA they are more flexible with decisions
Interaction of reward system with hippocampus and related structures
VTA to nuc Accumbens, nuc accumbens to and from hippocampus
Works with formation of long term memories
LT memories facilitated by novel things, unexpected things
Difference in high trust vs low trust economies
Learn to trust via trial and error then through long term habit
The Trust Game
First player (proposer) is given money who can invest with another player (responder). The winnings
can be shared or not by the responder with the proposer
You can have confederate earn reputation (not give money back) OR just tell people that responder
reciprocates or not
VTA to Nuc Accumbens
When someone gives you money back the VTA NA system increases in activity (unexpected
reward)
If you give poor reputation to responder but still have them give money back there is no
increase in reward areas of VTA NA System
You don't respond the same to people with bad reputation as good reputation
Medial Temporal Lobe activity (memory of reputation) inhibits striatal signals when there is no
reason to be suspicious
There is a neurological basis for difficulty in changing social reputations and in stereotypes
existing
Medial prefrontal cortex (comes into play when thinking about people), dorsolateral prefrontal
cortex, oxytocin release
Oxytocin is involved in social bonding, friendship, trust, etc
Schizophrenia
1:35 PM
A class of disorders
First described by craiklen and bluler
Variability across and within an individual
Positive symptoms
Symptoms in addition to regular behavior
Hallucinations, delusions, disorganized thought process
Usually in auditory areas, usually people hear voices
Deluded beliefs that are outside realm of reality
Thoughts are scrambled, don't make lots of sense
Negative symptoms
Restricted affect
Not a full emotional range
Loss of drive
Little motivation
Poverty of speech
Can have episodes of positive symptoms then primarily negative
More negative symptoms is a worse prognosis, better at controlling positive symptoms
Most frequent onset is early adulthood
Mens onset peaks at 15-20
Women have another peak in late 40's
Speculated to be tied to estrogen interaction with dopamine, high levels of estrogen protect women
from onset, as E levels decline onset increases
In general schizophrenia is found more in men and have worse prognosis, more negative symptoms
Onset usually precipitated by a stresser
Military, college, leaving home
There ARE changes prior to onset, this is a developmental disorder
Schizophrenia prevalance is 1% (1 in 100)
In general when people present with Schizophrenia they have it for life (Not like depression)
Over 10 year course the symptoms degrade brain function then stabilize
Isolated instances of positive symptoms can happen but are rare
Still no cure, but some treatments
Suicidal thoughts are prevalent, voices in head are uncontrollable and people cant get away from them
Premorbid Signs
Prior to fitting the full diagnostic criteria there are indicators for high risk
Niemi et all 2003 high risk study
Schizophrenia runs in families, high risk for family members
Identify high risk families and look for premorbid signs
Developmental delays
Motor abnormalities
Poor social competence
Personality traits
Become more pronounced as you age
Preschizophrenic males show externalizing behavior that is much worse than females and
controls
Preschizophrenic females internalizing behavior increases drastically
Cognitive impairments
Predate onset of disorder
Impairment in prepulse inhibition
P50 auditory evoked response
EEG cap on, look for response to auditory signal
Shows exaggerated response
Can be much more diagnostic, could hopefully lead to earlier diagnosis and prevention
Prevalence
Regional differences
More common in northern climates
Scandanavia, russia, canada, etc
Less common in equitorial areas
Seasonal differences
Born in late spring and early winter (in northern hemisphere) have significantly higher risk of
schizophrenia (and vice versa in southern hemisphere)
Change in prevalence in subtype of schizophrenia and severity of symptoms
Manual for diagnosis to give standards and metrics
Prior to new sets there were different classes of schizophrenia based on symptoms
Catatonic, paranoid, disorganized, undifferentiated etc
Catatonic schizophrenia viewed as most severe, but is almost never seen now
Johnson et al- drugs that treat symptoms might prevent further degeneration
Adoption study
Kety- 1988, 1994
Look at adoptees that become schizophrenic
Adoptive relatives show normal schizo percentages
Biological relatives have much higher percentage of schizo cases
Schizophrenia related to schizotypal but not schizoid personality disorder, not related generally to psychosis
Don't see high rates of manic depressive disorder, bipolar disorder, etc
Schizotypal disorder- asocial, withdrawn, show bizarre behavior (hoarder, paranoia, etc)
Schizoid- asocial, withdrawn, but not exhibiting bizarre behavior
Gejman et al 2010
Molecular genetics indicate uncommon copy number variations (mostly deletions) and polygenic inheritance
Related to autism and bipolar disorder with respect to genetics (genes seem to be related)
Harrison and Owen 2003
7 genes identified as key, 5 have been replicated
Genes are involved with NMDA receptors (learning memory) Glutamate, developmental processes,
(formation and maintenanceof synapses, synaptic function, PSYN Genes, RGS4 gene)
Abnormalities in neural structure
Studies on anti psychotic nave schizophrenic individuals
Almost all schitzophrenic individuals are medicated once they present symptoms
Chronic medication could be causing changes in brain instead of the disease causing changes
Want to study nave schozophrenic individuals so you get good information not tainted by drug treatments
Schizophrenia Page 41
Positive symptoms- in addition to what is normal behavior

Negative symptoms- absence of normal behavior
Pre 90's- little understanding of +- symptoms, not much cohesion between
literature and neuroscience
Commanalities across gene impairments- families of genes that can be impaired

and cause difficulties
Want to study nave schozophrenic individuals so you get good information not tainted by drug treatments
Soft Neurological signs- signs that can indicate something is different and wrong
Problems with reflex
Problems with eye movement
Small minor motor issues
Children with delays in walking, talking, etc other developmental delays
In schizophrenic individuals there are a lot of soft neurological signs
Structural abnormalities
Enlarged ventricles
Spaces with cerebrospinal fluid in brain
Proven with twins that are discordant with schizophrenia
Small caudate nucleus
Lateral ventricle is enlarged -->smaller caudate
Dorsolateral prefrontal cortex
Smaller in size, area involved in working memory, strong cognitive area
Thalamus
Smaller than normal- leads to enlarged ventricles
Medial temporal lobe including amygdala, hippocampus, and entorhinal cortex
Abnormalities in dendritic trees, smaller than normal
Lots of forebrain structures impaired, and high level structures are smaller than normal (either not
developing properly or degenerating)
Changes in neuronal organization
Cortical subplate
Thalamus makes connection with cortical subplate, cortical subplate degenerates when cortex is ready
to connect to thalamus
In schizophrenic individuals cortical subplate neurons are still present and active
Cell bodies in middle of white matter
Abnormalities seen in prefrontal areas
Related to migration issues
Markers NADPH-d and MAP2 used to view abnormal neurons
Entorhinal cortex and hippocampus
Entorhinal is input and output of hippocampus
Miswired in schizophrenic individuals, axonal connectivity is present but disordered
Excitatory and inhibitory neuron balance
Stain for gaba vs glutamate- balance is off for schizophrenia
Too much inhibition in prefrontal areas, too much excitatory further back (occipital areas)
Not what you want to see in typical brain
Metabolic activity
Decreased activity in medial frontal cortex, cingulate gyrus, medial temporal lobe, corpus callosum, ventral
caudate
Caudate, MTL, etc are smaller than normal, so using a standard brain template dilutes the results
Increased activity in left lateral temporal and occipital cortices
Hypofrontality
Whole prefrontal area is more inhibited, less activated, less attentive and less cognitive activity
Dopamine hypothesis
Schizophrenia is result of too much dopamine activity
Evidence for
Action of neuroleptics (antipsychotics) correlated to ability to block dopamine receptors
Chronic abuse of amphetamine or cocaine
Dopamine agonists
Cant tell difference between schizophrenic and cocaine/amphetamine binge
Not permanent, except that this is an area that is drug sensitized
Once you have psychotic drug break it becomes more likely to happen with less drugs
Psychosis tends to be paranoid
Heavy use of PCPA, glutamate antagonist
Induces psychosis, binge looks like schizophrenia
Psychosis tends to be delusional grandeur, super human
Evidence against
Postmortem studies
Increase in D2 receptors in striatum
Dopamine system adapts with homeostatic mechanism
Levels of dopamine metabolite HVA in Cerebrospinal fluid
Indirect measure of dopamine levels
Failure to find evidence for increased turnover, no increased levels of HVA
HVA concentration in CSF is negatively correlated to degree of cortical atrophy and
ventricular enlargement, suggesting decrease in dopamine turnover
More atrophy=less HVA
Decreased dopamine turnover in schizophrenic individuals with strong signs of brain
degeneration
Opposite of what is expected with dopamine individuals
Un-medicated schizophrenic individuals show normal or decreased HVA in CSF
^^^^^^^^ÂLL OF THIS IS INCONSISTENT WITH DOPAMINE HYPOTHESIS
PET Scans reveal no consistent changes in dopamine receptors
Action of atypical neuroleptics
Do not have strong dopamine antagonist activity but still effective for treating
schizophrenic symptoms
Treatment
Three dopaminergic systems
Nigrastriatal
Substantia nigra--> Striatum (caudate putamen)
Mesolimbic
VTA--> Limbic Systems (Nucleus Accumbens)
Mesocortical
VTA--> Cortex (prefrontal)
Neuroleptics
Halperidol, chlorpromazine
Initial increase in firing rate of dopamine neurons in nigrostriatal and mesolimbic systems, chronic use
decreases firing to below pretreatment levels
Affinity to D2 receptors predicts efficacy
Effects on positive symptoms
Almost exclusively effect positive symptoms
Tardive dyskinesia
Motor tics
Look like subtler symptoms of Huntington's disease
Dyskinesia seen in unmedicated schozophrenics at 4-5%
Dyskinesia seen in unmedicated schozophrenics at 4-5%

Rate of dyskinesia is 15-20% in medicated schozophrenics
PERMANENT EFFECTS
Dysphoria, weight gain, etc
Nasty drugs to use, no one wants to be on them
Atypical neuroleptics
Clozapine, respiridone, olanzepine, quetiapine
Looked like they could have effect on negative symptoms but so far unfounded
Only affect mesolimbic and mesocortical system, not the nigrostriatal system
DOES NOT show tardive dyskenesia
Low affinity to D2 receptor, high affinity to D4 receptor, very non-specific
Affect all kinds of neurotransmitters and neuropeptides
Messiness of drug seems to be a key factor in how they work to treat schizophrenia
Effects and compliance
Only on negative symptoms
Better compliance, not as dysphoric, but still not great
Side effects- agranulocytosis (clozapine) leads to liver failure (fatal)
Usually shows up early
Proportion of individuals ~30% that dont respond to drugs
Other possible pharmacological therapies
5-HT3 receptor antagonists (serotonin)
Glutamatergic agonists
Could cause seizures or cell death
Glycine stimulating drugs
Treatment resistant schizophrenia
Gamma (30-80 Hz) Synchrony abnormalities as indicator of positive response to drugs
Normal individual shows high levels of gamma waves when problem solving
Schizophrenic individuals have abnormal gamma waves
Attempt to speed up process of finding drug that will work, early detection of a few days vs several weeks
If drug is effective it decreases abnormalities in gamma wave relatively quickly
Role of family treatment in schizophrenic individuals from families with high expressed emotion
When having first psychotic episode if family is "freaking out" with LOTS of emotion prognosis is not good for
schizophrenic individual. Volatile emotional family environment is detrimental to schizophrenics
Family therapy to educate and inform has been shown to be very beneficial
Cognitive therapy
Rector and Beck 2002
Delayed effects, can take up to a year
Cognitive restructuring
"This is how you need to think, how to manage illness, how to know when you are having delusional
thoughts."
Can ameliorate or get help with issues when they know delusions are coming on
Theories of Schizophrenia
Neurocognitive theory
Schmidt et al 2011
Cognitive effects predate onset of illness
More negative symptoms show more cognitive issues
Prediction of outcome of disease is more linked to cognitive issues and negative symptoms
Positive symptoms are not as good a predictor of poor prognosis as negative symptoms are
Mediating role of social cognition, impact of neurocognition on social cognition
Links between many different hardcore cognition tests relate to neurocognition and functional outcome
(Psychological and social) Social cognition is bridge between neurocognition nd functional outcomes
(Emotional recognition, PFA, SCST etc)
Impaired neurocognition impairs social cognition, impairs functional outcome.
Carlson's thalamic filter theory (for positive symptoms)
Thalamus is filter for sensory input, how much sensory info gets to cortex is function of thalamic function
Thalamus is reduced in size, positive symptoms related to lack of filtering
Filter is controlled by NMDA and glutamate receptors
Filter is normally opened and closed for normal function, schizophrenics cant close filter down to reduce
sensory inputs
Too much dopamine inhibition from VTA and SN to basal ganglia then does not inhibit GABA path from basal
ganglia to thalamus
Also caused by not enough excitation from GLUTAMATE to Basal Ganglia, still shuts down GABA inhibition
path from BG to Thalamus
Hyperdopamine-hypodopamine theory
Increase in dopamine activity in striatum and positive symptoms
Decrease in dopamine activity in frontal cortex and negative symptoms
Less activity in frontal cortex
Link between two systems
Often see a lot of positive symptoms in acute psychotic break, then show more negative symptoms
^Âddition to Thalamic filter theory
Neurodevelopmental hypothesis
Onset is adult, but there are premorbid signs
Genetic or epigenetic event during early dev. (likely second trimester)
Cortical subplate issues (subplate is still there in adult brain, malfunction of development)
Early environmental factors
Stress precipitates disease in adulthood, but disease was always present
"two-hit hypothesis"
Something early in development like immune event that targets brain (first hit)
Second hit comes in early adult hood, immune insults, environmental stressors, or genetics (Feigenson
2013)
Focuses on glutamate hypofunction
Mimics et al 2001
Genes involved in presynaptic function
PSYN Genes and RGS4 genes
RGS4 protein declines, less stable synapses and impaired function
If a synapse is not fully functional it is likely to die or be pruned
More pruning lowers synaptic function below threshold of disease
Consciousness
Thursday, December 05, 2013
1:40 PM
Phenomenological mind is what most of us think of the thoughts going through your head
Something about the chemistry and biology that makes consciousness happen
Defining consciousness
1994 interdisciplinary conference
NO solid definition in neuroscience of what consciousness is, dont want to restrict R&D
Examples of consciousness
Conscious awareness, self awareness
Notion of agency
If we are conscious we are in control of our own behavior
Consciousness as a state
Includes sleep and wakefulness
Dreaming is different consciousness than wake
Altered consciousness conditions
Drug use, comatose, anesthesiology etc.
Studying consciousness
Not restricted to one approach of paradigm
Difficulties in studying
Third person data is what observers want to study as scientists, but consciousness is
fundamentally first person
Ethical issues, consciousness across species
Manipulating consciousness can be hazardous, we dont understand what we are
working with
Applied issues
Anesthesiologists very interested in eliminating consciousness
Deep comatose patients that come out and report full and accurate information
Approaches to studying consciousness
Binding problem
Parallel processing and sensation and perception, how they work together
Proposed components of awareness
Crick 1984
Oscillations in neuronal activity
Recording a neuron shows action potentials that oscillate
Synchrony of oscillations
Gray et al 1989
Single cell recording in visual cortex of cats
Oscillations become synchronized when different neurons are processing
unified information
Synchrony works across senses (engel and singer 2001)
Gamma frequency in humans (40 hz waves)
People with misaligned eyes (one eye focused off to side, other normal) learn to use
only one eye
Eye that is used is synchronous, eye that is not used is NOT synchronized
Dehaene and Changeaux 2011
Global network for consciousness
Information is globally available via a network of neurons with long range
axons linking areas of brain
Anesthesia and consciousness (Mashour 2011-13)
Disintegration of cognitive processing
Consciousness Page 45
Disintegration of cognitive processing

As someone goes under anesthesia under imaging you see decrease in
connectivity in thalamocortical networks
Notion of agency
Gazzaniga and localization of function
Split brain patients (cut corpous callosum to prevent generalized seizures)
Initially show conflict between hemispheres
Left hemisphere is the interpreter, can name things, read, etc
Right hemisphere cannot read, name things, etc
Over time the conflict goes away, and left hemisphere becomes
more dominant controlling behavior
Left hemisphere controls agency
Conscious states in sleep
Difference between REM sleep and wakefulness is sensitivity to external stimuli
and memory
Late potentials like P300 wave (memory formation wave) are abolished
during REM
Hallucinogens (psilocybin, lsd, etc)
Kometer 2013 5Ht2A receptor for serotonin
Consciousness Page 46
Non-Cumulative section
Sleep and dreaming 15pts
Learning and memory 15pts
Schizophrenia
15 pts
Consciousness
5 pts
FINAL INFORMATION
1:10 PM
1. Name three parts of the neuron and describe generally how information is transmitted?
Dendrite, cell body, axon, axon terminal
2. What do glia do and describe a disorder of myelination?
Insulate cells (myelination)
Schwann cells in periphery
Oligodendrocyres in CNS
Multiple Sclerosis (autoimmune disorder, de-myelination in CNS , result of childhood viral
exposure
3. What is the epigenome and give an example?
Environmental factors influencing how genes are expressed
Regulates gene function w/o changing genetic sequence
Cancer, obesity, addiction?
4. Give three reasons that non-human animals are used in research.
Simplicity (animal brains are less complicated than human)
Efficiency (lifecycle of rat for instance is much shorter than human, allows for transgenerational
and large scale study, also cost is much lower)
Similarities across brains (many functions are similar enough to be transferrable)
Ethical regulation from Institutional Animal Care and Use Committee IACUC
5. Name four different parts of the peripheral nervous system.
Spinal Nerves, Cranial Nerves, autonomic ns (sympathetic (arousing) and Parasympathetic
(calming))
6. How do chemically-gated and voltage-gated channels open?
7. Give examples of a passive, evocative and active interaction of genes and the environment?
8. What are levels of analysis with respect to experimental approach to the study of the brain/mind?
9. What are a sulcus and gyrus?
Sulcus is a fold, gyrus is "hill" between the fold
Gyrus is wrinkle, sulcus is fissure
10. What three structures make up the hindbrain?
Medulla, pons, cerebellum
11. What two structures make up the tectum in the midbrain?
Superior and inferior colliculi
12. What three general structures or systems make up the forebrain?
Limbic system, basal ganglia, cortex
13. What are the lobes of the brain and what do they do generally?
Frontal lobe (Motor/executive function)
Parietal lobe (tactile function)
Occipital Lobe (visual)
Temporal lobe (visual, auditory, gustatory)
14. Who were Golgi and Cajal?
Golgi believes NS is composed of nerve net
Cajal develops neuron hypothesis, NS composed of discreet cells, neurons are units of brain
function
15. How does the synthesis of catecholamines and the synthesis of neuropeptides differ?
Catecholamines (Small molecule) synthesized in cell body w/ slow axonal transport for packaging
and release
Neuropeptides (large molecule) prepropeptide synth in cell body, fast trans to axon terminal for
cleavage into neuropeptide for package/release
16. What are two different modes of termination of action of neurotransmitters?
Reuptake by presynaptic terminal or enzymatic chemical breakdown in synaptic cleft
17. How does the NMDA receptor work?
Double gated
Excitatory, need depolarization and glutamate binding to it to open channel
18. What is the function of second messengers in the neuron?
Play role in metabotropic receptors and more complex receptors
19. Define agonist and antagonist.
Agonist drugs mimic effect of NT
Antagonist drugs block effect of NT
20. What is the key molecular change underlying sensitization in the Aplysia?
Interneuron makes axoaxonic connection to terminal of sensory neuron
No molecular change in Calcium channel, but still allowing more Ca in to excite larger EPSP
Broader Action Potential caused by potassium flowing out (Spike broadening)
Potassium channels become phosphorylated
Axoaxonic connection releases serotonin from interneuron to cause second messenger
cascade (metabotropic receptor) results in phosphorylation
21. How is long-term potentiation induced in a neuron?
First doing test pulse and look at EPSP, high frequency stimulation, wait a little, then another test
pulse shows larger EPSP
22. What is the Nernst Equation and what does it mean?
Ek = RT ln [K+]o
F
[K+]I
FINAL REVIEW Page 47
30 multiple choice
4 5-point questions
Cumulative section
20 3-point questions
1 15-point question
F
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[K+]I
Describes equilibrium potential of single ion by making it completely permeable to that ion
(simplification of goldman eqn)
What do sodium and potassium do during the action potential and why?
Sodium channels (voltagegated) open and sodium rapidly enters cell (depolarization)
Potassium channels then open and K leaves, overshoots resting to hyperpolarize neuron (leaky
channels)
Ions diffuse back to equilibrium
What are the absolute and relative refractory periods?
Absolute- new AP cannot be elicited because non-voltage gated sodium channel is closed
Relative- axon in later phase of an AP when increased electrical current is required for another
potential (K channels still open)
What is a postsynaptic potential and describe its properties?
Change in polarization due to stimuli (NT) that can excite (EPSP) or inhibit (IPSP) formation of new
action potentials
PSP's summate over time and space (more faster or more in closer area more likely to produce AP)
PSP's are graded in size, transmission is almost instantaneous
What are the steps in the axon terminal that cause a neurotransmitter to be released into the synaptic
cleft?
At axon terminal calcium activates microtubules that cause NT release
What causes an action potential to start?
1. EPSP's and IPSP's reaching threshold via summation of time and space
What is a tonic-clonic (Grand Mal) seizure?
Seizure across the whole brain, loss of muscle control and consciousness, muscles contract then
convulse.
How is the neural tube formed?
Neural plate forms, thickening of cells
Slowly neural plate curves in on self and fuses to form neural tube
Formed 25 days post conception
Initiated by retinoic acid and retinoid receptors
High levels of retinoic acid causes neural tube defects
Growth factors- acting on receptors facilitating formation of tube
Fibroblasts and transforming GF
Neural tube is about at midbrain area
Grows forward and back to form forebrain
Describe two key factors involved in neuronal migration?

Radioglial cells in cortex, extracellular matrix
What is apoptosis and when does it occur?
Cell death, during differentiation
What kind of dendritic spines are seen more frequently in mental retardation? Give examples.
Long spindly spines more frequently seen in downs syndrome, not as good electrical connectors
How does neuronal migration occur in the cortex?
Cortex- radial glial cells form pathway for moving cells
Six layers, inside out organization
Chemical signaling in new neurons and radial glial cells
Extracellular matrix is chemical soup providing signals for neurons to travel along via chemical
attraction or repulsion
What brain changes are seen in autism?
Cell migration issues
Smaller cerebellum with missing dendritic trees
Decreased activation in orbitofrontal cortex
How do benzodiazepines work to alleviate anxiety (describe on a molecular level)?
Bind to gaba receptor
1. Excitation produces influx of Cl- which hyperpolarizes neuron
2. GABAa has two sites
i. Sedative hypnotic site- alcohol and barbiturates directly influence cl- influx
ii. Antianxiety site- Benzodiazepines, enhances binding effect of GABA
How do stimulants generally affect brain function?
Increase motor behavior, elevate mood and alertness
Increase cell metabolic activity
What key structures and pathways mediate the addictive nature of drugs?
Dopamine and gaba projections from VTA and Amygdala to Nuc. Accumbens
How does a steroid hormone work?
A steroid hormone works by crossing cell membrane and acting on receptor in nucleus of cell by
turning on or off a gene
Given an example of an organizational and activational effect of a specific hormone.
Testosterone
Organizational effects in early development
Activational effects in adulthood, often behavioral and temporary
40. In what behaviors is the nucleus accumbens involved?

Involved in all fundamentally motivating behavior
Addiction, reward processes
41. What kinds of behaviors or thoughts activate the insula?
Emotion and autonomic functions, plays role in emotional disgust
42. What is a hypercolumn?
group of columns that contains all of the orientation biases, AND both left and right occular
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
53.
54.
55.
56.
57.
58.
59.
60.
group of columns that contains all of the orientation biases, AND both left and right occular
dominance
What is meant by topographical organization in the cortex and give an example?
Adjacent parts of the world are in adjacent areas of the brain,
What is a center-surround receptive field and what specific neurons show this type of receptive field?
Ganglion cells show center surround with on center or off center (on center cell excited with
stimuli ON CENTER, inhibited with stimuli off center and vice versa for off center cells)
Where is Brocas area and what is it involved in?
Broca's area is in frontal left cortex, involved in speech production
Where is Wernickes area and what is it involved in?
Wernicke's area in left posterior temporal cortex involved in comprehension of speech
What is the muscle spindle organ and how does it work?
Describe four pyramidal signs.

What is the degeneration observed in Huntingtons Disease?
1. Atrophy of basal ganglia
What is the degeneration observed in Parkinsons Disease?
1.
What is the drug treatment for Parkinsons Disease?
What are the cell layers in the retina?
What is single cell recording?
How does the hypothalamus control the anterior and posterior pituitary gland?
What are the Mullerian and Wolffian Systems and how do they develop?
What is the role of the medial prefrontal cortex and insula in processing of other humans?
How might tricylic antidepressants work in depression?
What type of neurons do you see in a column in the visual cortex?
1. All types of neurons, hypercomplex, complex, and simple
What structures are part of the basal ganglia?
What is the most interesting fact that you have learned in this course and why is it interesting?
Long questions
1:13 PM
1. What does dopamine do? Discuss different aspects of its function and speculate on a general brain function for this
neurotransmitter. (A good answer to this questions will not just consist of a listing of functions but also include some
synthesis across functions.)
2. What do you think might be neural or neurochemical distinction between a perception and a hallucination? Use
material from the course to support your ideas.
a. Perception is external, hallucination is internal.

3. Imagine that someone manages to intake so much sodium that they increase the extracellular content of sodium in
their central nervous system. How would this impact the electrical activity in the brain? Be very specific about
movement of ions and involvement of channels.
4. Tom was sitting at a table and saw a bottle of tequila. He reached out and grabbed the bottle and proceeded to drink
a fair bit of it. Fairly shortly, he got dizzy, stumbled out of his chair, fell into his bed, and fell rapidly asleep. What is
happening in Toms brain during this scenario? You will need to speculate but be as specific as possible.
Be creative, use information, develop arguments, etc

Intro To Neuroscience Class Notes

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PPT for unit 1

Tuesday, August 27, 2013

Power Points Page 1

Communication and Adaptation

Previous lecture review questions

NS must change to learn something, some kind of adaptation in neuron or

LAST CLASS REVIEW

Test 2 notes Page 4

Test 2 notes Page 5

Development and Developmental Disorders

Next paper due next Tuesday

Test 2 notes Page 6

Will have abnormalities and retardation, degree can vary

Development of the Embryo

Neurotransmitter type becomes differentiated

Compare contrast PKU and Downs

Test 2 notes Page 10

Fetal Alcohol Spectrum Disorders

FASD caused by alcohol exposure

Test 2 notes Page 11

Symptomes and prevalence

function to manifest in behavioral symptoms

Test 2 notes Page 13

MANY are developmental and happen very early

Test 2 notes Page 15

Test 2 notes Page 16

Drugs and Addiction

Test 2 notes Page 17

A) Drugs are classified by most prominent psychoactive effect

a) Selective serotonin reuptake inhibitors

Test 2 notes Page 20

A) Becomes a compulsion, reflexive use

no concept of wrong doing while on drugs

Test 2 notes Page 22

General Properties of Sensory Systems

Test Three Page 23

General Properties of Sensory Systems

Test Three Page 24

iv. Organization of striate cortex

Test Three Page 26

Test Three Page 27

a. Prevalence of different symptoms depends on corticostriatal loops

Test Three Page 29

Emotion and Motivation

Final Monday dec 9th

Test Three Page 30

Gender difference in sexual orientation spectrum

Hypothalamus of homosexual males differs, is inbetween hetero males

Test Three Page 31

Mood and Anxiety disorders

Test Three Page 32

Did not cure schizophrenia but it did alleviate depression

Test Three Page 33

Circadian rhythms and sleep wake cycle

Sleep and Wakefulness

Post-test Three Final Page 34

Eve Martyr- neural circuit that controls stomach of crab

FINAL MONDAY DECEMBER 9th 12:30

Three systems work together to modulate cycle

Post-test Three Final Page 36

Learning and Memory

Point of having a brain is to learn and adapt to environment

Multiple Memory Systems