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Basic Neuroanatomy

- Natural law: what should happen according to God


- Buddhism has the least trouble with the sciences
Sections
- Midsagittal: cut right down the midline
- Coronal: looking head on at face, frontal
- Cross sections: section of spinal cord
- Gross neuroanatomy:
o The act of diseecting brains to understand brain structure

Terminology for laterality


- Lateralization: left hemisphere is functionally different from right hemisphere
o Male humans more lateralized than female humans?
- Unilateral: one side of brain
- Bilateral: both sides of brain
o Ex. Bilateral implantation of cannuli into nucleus accumbens
- Ipsilateral: on same sides of brain
- Contralateral: on opposite sides of the brian
o Ex. Contralateral/decissation of axons from spinal cord
o If you move your pinky on the right hand, the motor cortex in your left
brain controls it
Motor projections in humans are contralateral
- Language is lateralized (especially in males)
o In left hemisphere for right handed people
o In right hemisphere for left handed people (60% of the time)

Development of Brain and Spinal Cord


- Dorsal/coronal section of human embryo
- Neural plate: flat, center part
- Neural groove: results from invagination of neural plate
- Neural tube: results from closing of neural groove, results in brain, spinal
cord, etc.
Major Division fo the Neuraxis
- Neuraxis: entire neural tube, which gives rise to the entire CNS during
embryonic development
o Bottom = spinal cord
o Hindbrian = metencephalon, myelencephalon
o Midbrain = mesencephalon (midbrain), 95% of neurons that make
DA as transmitter
o Forebrain = telencephalon (cortex), diencephalon (thalamus,
hypothalamus)
Where Neuraxis Dvisions End Up in Adult Brain
- Still have division of neuraxis
o Metencephalon = pons (bridge)
o Myelencephalon = medulla

Cerebroventricular System
- Hollow part of neural tube becomes cerebro-ventricular system
- Four main ventricles
o I,II: in forebrain (telencephalon)
Lateral ventricles
o III: in hypothalamus
o IV: in the brain stem
- Cerebral acqueduct (acqueduct of sylvius) connects ventricles III and IV
o Acqueduct carries water (California)
- Ventricals circulates CSF
o Excess CSF results in hydrocephalus
Squishes brain
o Treatment: apply shunt

Human Cortical Gyri and Sulci/Fissures


- gyri: hills
- Sulci: valleys
- Meninges
o Meningitis: inflammation of meninges
- Neurosurgeons get worried if tumors are in left hemisphere
o Because language is in there
Wenirckes = BA 22
- Fissure: a long valley/sulci
o Central fissure: divides frontal and parietal lobes
o Lateral fissure: divides both the frontal and parietal lobes (above)
and temporal lobe (below)
- Why does our brain have wrinkles?
o Squeeze large amount of surface area of cortex into small volume
- Why are we so smart?
o Brain size? No
Dolphins, Neanderthals, have larger brains than us
o Not wrinkles
o No magic structure, basic wiring pattern is the same
o Gene expression
Most of genes are same, just which ones are turned on

Lobes of the Cerebral Cortex


- Einstein had a particularly large parietal lobe
- Longitudinal fissure: separates left and right hemisphere
- Doplhins have larger temporal lobes (kind of like brain is squished
in/deformed inwards)
o Why do they have large temporal lobes?
o Echolocation
- Central fissure: frontal lobe and parietal lobe
- Human Cortical Zones.
o Primary Sensory Zones and
o Secondary/Tertiary Association Zones for Each Modality

Cortical Components of the Motor System


- Motor Cortex in Humans:
o We have Primary, Secondary, Tertiary, Quaternary Motor Cortices
- ADHD: shows decreased activity in the prefrontal cortex
o Adderoll increases PFC activity
- The more forward you go, the more abstract function gets
o Front = executive function
- Motor homunculus: a map of the motor cortex in the human brain that
represents the amount of cortex dedicated to each body part
o Rat is known as a ratunculus
o Area devoted to motor function is proportional to amount of use
Why if face so large?
Social communication aka emotions
o Raccoon-unculus and Coatimundi-unculus

Cortical Compoenents of the Somatosensory System


- Simunculus: the homunuculus analog for monkeys
- Prefrontal cortex is smaller in rats
o Marshmallow test:
Ones who ate marshmallow had impulsivity control problems in
the future
Sensory and Motor Areas of the Cortex
- 30 visual areas
- Why merge somatosensory and vision?
o Hand eye coordination, stand upright, balance
o All the time monitoring body and getting feel for where it is in space
- Drop electrode stimulation:
o Out of body experience

Association Cortex
- Association Cortex: Whats left after you map out clearly sensory and
clearly motor cortex
- whats left is association cortex
o Area of brain which particularly grew in leading to evolution of humans
- Much has been made, for a long time, of the relative increase in association
cortex in comparing simpler to more complex mammalian brains
o Amount of cortex dedicated to association cortex gets larger and larger
o Where growth occurred evolutionarily, why humans are smarter
- Animals not in line, but represent stages of cortical evolution
Brain Evolution
Vertebrate Brains
- Fish: dont have cortex
- How is cortex define in humans? Has layers
o Bunch of cells thick
Strata in valley of rock
Each layer has its own type of cell
- Dolphins only have five layers, humans have 6
o 6 layer = neocortex
o Cortex first appears in reptiles
Birds have reptilian brains (they evolved from dinosaurs)
- Tree of Life approach to brain evolution: not really correct, but useful
o THIS DID NOT HAPPEN
These are EXISTING species
o We like to think complexity increased
We did not come from monkeys
We came from a common ancestor
We did not go from codfish, to frog, to shrew, to horse
o Not a linear progression rather
- A more correct representation of brain evolution
o Is branching out like a tree, from common ancestor
o The brain is a rube-Goldberg machine:
Constantly adding and tinkering
If its not broken, dont fix it
o We have common ancestors

The Tasmanian Tiger


- The Tasmanian Tiger, an extinct marsupial
o Went extinct in 1936
o Very few where brain was removed
o Cant cut up the brain because there are very few in the world
o Thylacine: more proper name for the Tasmanian tiger
- The Tasmanian Devil, still present but highly endangered
o Tasmanian tiger vs. Tasmanian devil
Endangered due to cancer of the mouth/head region
o Get so large they cant eat anymore
- Berns 2017 (Emory Study)
o Reconstruction of the Cortical Maps of the Tasmanian Tiger and
Comparison to the Tasmanian Devil
o Recent Emory research related to brain evolution
o Used dti: diffusion tensor imaging
Water diffusion in brain, sign of white matter tracts
o Both Tasmanian tiger and Tasmanian devil (as well as north American
possum) are marsupials
No one watched tigers back when they were alive, dont know
anything about their behavior
o Trying to make ideas based on brain connectivity
Tiger has more association cortex, should be smarter
Tiger was a predator
Brains of carnivores are more complex than brain of herbivores

Triune Brain Model


- Dr. Paul MacLeans Triune Brain: a very influential view
o We still carry all of the older, lower brain systems.
- Paul Maclean: psychiatrist, proposed the triune brain model, back in the
60s
o Idea is that our behaviors might still be controlled by more ancient
areas (reptilian and neomammalian brains)
o Wrote The Triune Brain in Evolution
- The Truine Model:
o R-complex: reptilian, basal ganglia, caudate, putamen, nucleus
accumbens
Oldest: 284-286 milliion years ago
Regulates hunger, temperature control, fight-or-flight response
Shared with reptiles such as fish
o Limbic system: paleomammalian
Papez: neuropathologist, saw changes in emotion if
tumor/lesion in specific area
Showed how areas were connected together
Coined the term limbic system proposed as brain
system for emotion
Very controversial at the time
Evolved during Jurassic period, 206-144 million years ago
Regulates: mood, memory, hormone control
Shared with older mammals: dogs, cats, mice
o Neocortex: thought required for complex thought
Evolved during Eocene and Oligocene Epochs. 52-24 million
years ago
Regulates: logic and though required for complex social
situations
Shared with monkeys and chimpanzees
- PAUL MACLEAN
Hominids
- Where did humans originate?
o Africa
- Pan troglodytes
o Chimpanzees
o What is a troglodyte?
Beings that live underground
- Neanderthals
o At some point in history there were multiple humans
o Most of them were dead ends
o Discovered in nenderthal valley in Germany
o Actually had bigger brain size than us
Not stupid brutes we thought they were
- Homo florensis
o Hobbits

Hominid Brain Volume:


- extremely rapid increase in volume in the last 1.7 million years
- Endocasts: blow latex rubber into skull, used to estimate brain volume
- Less than 2 million years ago huge, exponential growth in brain size
o Must have been a selective pressure
o Social bonding/communication was very involved
o Big brains tend to go with complex society
o Need a large brain to socialize
o Need to recognize people/faces (FFA)
o Need to recognize emotions
- Individuals that had larger brain were better at this, had more offspring
o Self feeding proposition, social structure and brain structure driving
each other (positive feedback)
- Two views:
o 1. evolution (society)
o 2. religion (the finger)
- Neils Slide:
o What drove the remarkable, relatively quick, increase in hominid
brain volume in the last 150,000 years?
The Darwinian view: some sort of selective pressure.
o What selective pressure? Environmental change? That is too slow.
o Many have suggested a positive feedback between social group size
and brain volume.
That is, having a larger brain was an advantage in a large social
group.
In turn, larger brains enabled more complex social interaction.
This positive feedback led to a relatively rapid increase in brain
volume along with the development of more complex societies.
o The finger view: God reached in and directed this relatively rapid
increase in brain volume.
Origin and Evolution of Life
- The dominant theory at present of the origin of the universe is that it began
very small (1 cm or less), and extremely rapidly (less than milliseconds) grew
in size.
- In a balloon
o The universe is on the surface of the balloon
o Not the inside
o If ballon expands, two dots expand
o Currently MOST accepted (not all) theory by physicists

Red Shift
- The original evidence for the expansion of the universe was the red shift
seen in the light of stars.
o If moving away from you, wavelength longer, red shift
o If moving towards you, wavelength shorter, blue shift
o We are a spot on the outside of the balloon
o So everything is moving away from everything
o Mass in universe is enough to keep universe together though
o Proposed dark matter
o Cosomology: study of universe on a grand scale

Origin of Life (Abiogenesis)


- There are numerous scientific hypotheses for the origin of life.
- Although some are more dominant than others, no one hypothesis has yet
become the consensus among scientists.
- Abiogenesis: the process of which life originated
- Neils Slids: A major hypothesis has been that life originated from
physiochemical processes in place billions of years ago.
o Stanley Miller, a graduate student at the University of Chicago,
published a paper in 1953
o showed conditions simulating the early Earth environment could
produce amino acids, the building blocks of life
Miller Urey Experiment
- The experiment was actually done by Miller and a mentor, Harold Urey (Nobel
Prize, 1934).
o Urey gave the credit to Miller. A schematic of the apparatus is on the
left.
o An older Miller and the apparatus are on the right.
- Miller and Urey:
o Simulated environment of early earth
o Water, methane, ammonia, hydrogen gas, lightning
Found amino acids
- Inorganic molecules form organic molecules
RNA World
- Many scientists are currently favoring the RNA World hypothesis: the
early life was based on RNA, not DNA.
- RNA World: hypothesis that early life was based on RNA, not DNA
o life: self-replicating
o RNA is the simplest macromolecule to fulfill that
o Prebiotic chemicals form elements of RNA
o A little chemistry results in RNA

Panspermia
- Panspermia: theory that states that life originated on other planets outside
of our solar system, and was carried here on a meteorite, asteroid or comets
- Panspermia: life originated extraterrestially, from outside of Earth
- This is why NASA collects samples from comets/crashed meteorites
- Associated with 2 astonomers:
o Fred Hoyle
o Chandra Wickramasinghe

Charles Darwin
- Father: Robert Darwin, M.D.
- Paternal Grandfather: Erasmus Darwin (intellectual and abolitionist)
- Attended Unitarian church as a child
o Unitarian: avoid using terminology to refer to God, believe God is one,
open to all religions
5 Year Voyage of HMS Beagle
- While Darwin was on the voyage he shipped back many skins of different
animals
- HMS Beagle: ship travelled on by Darwin in his 5 year voyage the world
- around
- Darwins Account of the Voyage, published in 1839
o Voyage of the Beagle

Galapagos Islands (Now proprety of Ecuador)


- Darwin DID NOT get his idea of natural selection while on the Galapagos
islands
o Just a place he happened to visit
o He made observation there about birds
But it IS NOT where he got the idea for natural selection
- Started putting everything together after the trip
Down House
- After returning to England, Darwin married and eventually moved to a house
in southeast England, in the town of Downe, . He called the house Down
House.
o Being independently wealthy, Darwin never had a real job.
- Expert on Barnacles
o Well known in the scientific community

Theory of Evolution
- Erasmus Darwin, grandfather of Charles Darwin, had already thought about
evolution
o evolution being defined as descent with change.
o Others had as well. However
nobody had a natural explanation for how the change
occurred.
- Evolution: contemporary animals came from precursor animals that came
before, descent with change
o IDEA OF EVOLUTION DID NOT START WITH DARWIN!
o grandfather (Erasmus Darwin) had already defined a descent with
change
Threads of Darwins Thinking
1. The geology he saw on the Beagle trip, showing how the earth, and
presumably the environment, changed over time.
a. Darwin saw layers on cliff (geology)
b. Bones of animals in layers, geologists at time explained it with idea of
biblical flood
c. Ashore in Argentina, Darwin was impressed by how rocks, and fossils
in the rocks, occurred in strata. He also identified some fossilized teeth
of the extinct giant sloth Megatherium.
2. The finches in the Galapagos islands (although see the correction in a
following slide).
a. Saw finches in Galapagos islands
i. Found different types of finches (size of beak)
ii. Fit with what they ate on the island
b. Different finches on different islands had different beaks
i. Some people accept microevolution, not macroevolution
(Darwinian evolution
ii. Use finches as example
c. Microevolution: birds develop beak sizes but ARE NOT new species
d. Macroevolution: appearance of new species
e. How to define species?
i. Being able to successfully mate and produce offspring
3. Reading Thomas Malthus on population.
a. Thomas Malthus (An Essay on the Principle of Population)
cited by Darwin
b. English clergyman, how do you feed all these people?
i. given finite resources, continuous population growth would lead
to a decline in the general standard of living and socioeconomic
catastrophe
c. Carrying capacity: maximum population a place can sustain
i. From time to time there are crisis for a given species
ii. i.e. dinosaurs: meteor hit earth
iii. Threw debris up into air
iv. Blocks sun, cools earth
4. Breeding pigeons at Down House.
o Breeded pigeons
o Came up with really weird looking pigeons
o Darwins proof of concept lay in wheat, rice, cows, sheep,
chickens and pigeons: the products of domestication of wild
animals and plants by artificial selection.
Darwins Wife and Child
- Why didnt he go public with ideas?
- Darwins wife, Emma (also his first cousin), was a devout Christian.
o Many scholars think that Darwin sat on the idea of evolution by natural
selection for 20 years out of deference to Emma.
- Emma and Charles had 10 children.
o Their daughter Annie died at age 10, probably of tuberculosis;
o this greatly affected Darwin.
thought to have contributed to Darwins progressive loss of
religious faith.
- Thought that this is what made Darwin give up on religion
o How could a loving god let this happen?

Alfred Russel Wallace


- Alfred Russel Wallace, working in Indonesia independent of Darwin, but in
contact with him, also conceived of what Darwin called natural selection.
- Alfred Russel Wallace: scientists working in Indonesia, developed theory of
evolution independently from Darwin
- A deal was struck: Darwin and Wallace each presented a scientific paper at
the meeting of the Linnean Society of London, July 1, 1858
o Darwin published his book in reaction to competing theories by Wallace
o IN A YEAR!

The Evolutionary Synthesis of the 1940s


- These things nailed down Darwins theory even more:
o Knowledge of genetic transmission (DNA)
o Knowledge of mutation
o Experiments with X-rays and drosophilia
o Population biology
- These thing did not exist in his time, but supported his theory after
- Darwinian theory is not just evolution, it is evolution by mean of
natural selection
- Other people had evolutionary theory, but did not know how it went about
Selfish Genes (Richard Dawkins)
- Genes are selfish because their basic modus operandi (pass on the genes)
is selfish
- Bodies are just transport vehicles for genes.
Why are Many People Antagonistic Towards Evolution by Natural Selection?
1. Evolution itself contradicts their sacred scriptures
a. particularly the Abrahamic religions of Judaism, Christianity, and Islam
b. even the Dalai Lama doesnt accept the idea of natural selection
applied to humans.
2. Even for non-believers, the random nature of natural selection is
too nihilistic.
3. They think that acceptance of an atheistic, nihilistic view will
result in no morality,
a. anything goes, and chaos in the streets.
b. BUT, some research shows basic moral behavior is built in
c. But religion believes the natural view of people is sinful
Religious Antagonism
- Ontogeny recapitulates phylogeny
o Ontogeny: organismal development
o Phylogeny: evolutionary development
- EVOLUTIONARY BY MEANS OF NATURAL SELECTION
o Darwin: human beings evolved but god had nothing to do with the
process
o Theist: believes in god or gods
o Theistic evolution: evolution driven by the finger
o Deism: God exists, created everything, but had no part in universal
processes
- Some Orthodox Jews remain staunchly opposed to evolution
o Others are open to multiple interpretations of Genesis
- Islamics believe in microevolution and macroevolution
o HOWEVER, they do not believe humans are part of same scheme
o Rather, they are a unique and honored creation of Allah
- More orthodox creation of Islam
o Main tenet of Darwinism (there is no purpose, no direction, all random)
goes against Islam
- Hindus believe Gods intelligence pervades the universe
o Evolution is a manifestation of Gods intelligence
o Hindu belief is completely consistent with evolution
- HOWEVER, Hindus do not believe consciousness is a product of matter
o They believe matter arises from consciousness
- Buddhism does not have a problem with evolution
o Evolution is just another example of impernance
- HOWEVER, Dalai Lama cannot believe mutations are random
o Believes evolution is directed
o Again, the finger
- All religions have a problem with SOME DEGREE with evolution by natural
selection (aka random, not directed)
Brainjacking
Ichneumon Wasp/Muddaubers
- Ichenuemon:
o Family of wasps
Have ovipositor (Egg depositor)
Metal on tip like zinc
o Really bothered Darwin
How could an omnipotent God let something this terrible
happen?
- Mud-Dauber
o Kinds of wasp that paralyze their pray (spiders) and deposit living
spider in nest as food for young
Brainjacking
- Brainjacking: parasitic organism takes over nervous system of larger
animals, controls it as a zombie
o By brainjacking, I mean the ability of a simpler organism to
manipulate the behavior of a more complex organism by controlling
brain circuitry.
- Cricket suicide
o Worm grow within cricket, makes it really want to jump into water
Then worm grows out of cricket and swims off
- Snail zombies
o worms grow within a snail
o take over control of the snails brain, causing it to climb high in the
vegetation, where a bird consumes the worms
- Taxoplasma Gondii
Taxoplasma Gondii
- Toxoplasma gondii
o Protozoan parasite infects most warm=blooded animals
o Oocysts (oocytes encapsulated in cyst, allows for survival outside of
body cavity for some time)
o Ingested by intermediate hosts
o End up in muscle and brain
- Toxoplasmosis
o Disease caused by T. gondii
Acute infection usually mild or asymptomatic
Rarely flu-like symptoms, lymphadenopathy
Exceptions: immunocompromised, pregnant
When symptomatic, may produce hallucinations and
delusions in adult patients
o Chronic infection almost always asymptomatic but also untreatable
Human infection is extremely common
Estimated 22.5% US population, 33% of world

Toxoplasma and Rodents


- Long thought to be chronic infection with no effects
- Simply transferred to cats upon random predation
o Innate rodent fear of cats unaffected
- Field observation noted that rats with toxoplasmosis (Toxo) had decreased
neophobia
o Numerous later observations revealed that rats with Toxo were less
fearful of cats
o Specifically, less fearful of cat urine
- neophobia: fear of new things
o Rodents with toxoplasmosis showed decreased neophobia
o Less fearful of cats, specifically cat urine

Vyas 2007
- Behavioral changes induced by Toxoplasma infection of rodents are
highly specific to aversion of cat odors
1. Does Toxo alter the response of rodents to cat urine or cat odor?
o YES
o Looked at affect of toxoplasmosis of neophobia in rats
o Had 2 groups
o Control: uninfected rats
o Experimental: infected rats (5 weeks post infection)
o Released rats into circular arena with bases
1. home cage
2. rabbit urine
3. bobcat urine
o Tracked movement
o Rats infected had a higher relative occupancy in the bobcat
urine quadrant
o IMPORTANT:
Toxoplasmosis not only makes the rat no longer fear cat urine (if
that was the case they would spend equal time in quadrant)
But it made them ATTRACTED to it!
2. Does Toxo affect other rodent behaviors such as anxiety or learned fear?
o NO
o Studies affect of toxoplasmosis on:
1. anxiety
Unconditioned fear: looked at amount of time spent in
open spaces
2. fear
Pavlovian fear conditioning (tone with foot schock)
Measured freezing
o No Difference in unconditioned fear of an open space
o No difference in conditioned fear to a tone
3. Do Toxo cyst locations in rodent brains correlate with known neuroanatomy of
fear?
o YES
o Had parasites express luciferase
o Sectioned infected brains
Bioluminescence of brain slices compared to quantify tissue
density
o Side Experiment: LeDoux
LeDoux:
Showed amygdala responsible for fear conditioning
Linked (LTP) tone and footshock
Destruction of central grey removed freezing response
o Toxo parasites preferentially accumulate in the amygdala
- Systems for fear and sexual arousal closely linked
- Are the toxoplasma causing and interplay between these 2 systems?
House (PloS )2011
- Predator Cat Odors Activate Sexual Arousal Pathways in Brains of
Toxoplasma gondii Infected Rats
- Male rat:
o Signals from her (pheremones) picked up by vomeronasal organ
o Vomeronasal organ sends axons to medial amygdala
o Turns on cells in amygdala which then sends axons to the medial
preoptic area (mPOA)
o mPOA then sends axons down to brainstem
o Activates preplanned mating motor pattern
- ALL OF THIS IS SENSITIVE TO ANDROGENS
- Androgens: male sex hormones
- Estrogens: female sex hormones
-
1. Does Toxoplasma have an effect on neural activity in brain structures
involved in fear and sexual behaviors?
a. YES
b. Infected and non-infected male rats were exposed to cat urine or an
inaccessible estrous female
i. Then saced, sectioned, stained for c-Fos
ii. Focused on medial amygdala, ventromedial hypothalamus
c. Estrous cycle: rats dont have menstrual cycle, have estrous
cycle, become sexually receptive every 4 or 5 days
d. C-Fos: early and intermediate gene, oncogene (cancer gene), that
when neurons are active, the gene becomes activated
e. Looks at brain structures that are activated
i. Either fear pathway lit up, or sex pathway is lit up
f. Medial amygdala: involved in sex arousal response
g. Ventromedial hypothalamus: involved in defensive fear
response
h. More c-Fos labelled neurons found in medial amygdala when
exposed to cat urine
i. Cat urine turns on areas involved in sex
i. In rats infected with taxo:
i. Cat urine turns on medial amygdala, c-Fos labeling
increased
ii. Cat urine turns down ventromedial hypothalamus, c-Fos
labeling decreased

Sexual Selection and Evolution


- Why do peacocks have such intricate feather?
o From a survival standpoint it doesnt makes sense:
Slows them down, etc.
o its because of sex

Darwin Strikes Again


- 1871, publishes book: The Descent of Man and Selection in Relation to Sex
o Males compete for access to females
This is a selection mechanism for evolution
- Contemporary view:
o females: reproduction is much more costly
One egg per month
Much more costly to produce
o Gestation lasts a long time
- IF the costs of reproduction are higher in females than males,
o AND individual males differ in their value as mates,
o THEN females will be choosy.

Females in Control: How they Might Choose a Male


1. Sexy sons hypothesis: a female chooses a particular male phenotype to
increase her reproductive success. But this is a runaway process, and can
lead to excess (the males can look more and more weird).
o Choosing a male that looks attractive because hell produce good
babies
o This results in males that look more and more weird
o Runaway process
2. Handicap hypothesis: males who have survived with exaggerated features
must be really tough, and therefore have good genes.
o Handicap hypothesis: males who have survived long enough to
mate with exaggerated features, must have good genes
3. Resilence hypothesis: exaggerated features in male (feathers, gloss, dance,
etc.) are a sign of good health. Example: resistance to parasites.
o Resilience: exaggerated features in male show resistance to
environment, sign of good health
In Primates
- Male primates within mut-male groups (females mates with multiple guys)
have larger testes in proportion to body weight
o Produce more sperm, win out

Sociobiology
- E.O. Wilson: harvard biology, wrote Sociobiology: The New Synthesis
o Wilson: much of social behavior is determine by genetic evolution
Developed social biology -> evolutionary biology
o Communism:
Believed people to be blank slates (tabula rasa)
If you just organized society in the right way, people would be
happy
o Q: Why was name dropped?
Too inflammatory, implied people had no free will, went with
evolutionary biology
Because of the political/social furor, particularly by those
on the political Left (they didnt like the idea that a lot of
social behavior was genetically determined), the term
Sociobiology was eventually dropped, and the field
came to be called Evolutionary Psychology.
- anthropology, has 2 sides:
o 1. biological anthropologist: evoluntioary foundations of human
behavior
o 2. cultural anthropologists: everything is relative, relativism
- Biocultural anthropology: show how you can fuse biological and cultural
anthropology
- Core idea:
o Human brains evolved to fit conditions thousands of year ago
But were stuck with these brains in an era with very different
social and technological environments
- Professor David Buss: Evolutionary psychologist, studies human mate
attraction
o Males: place high value on physical attractiveness
o Females: place high value of resources males can provide
o Buss used a waist-hip ratio to judge attractiveness of women (WHR 0.7
is optimal)
Major predictor of heart problems
o BUT: WHR influenced by hormones in men and women
ideal WHR is different between cultures
Criticized as artifact of Western culture

- WHR influenced by hormones in men and women


- But, ideal WHR is different between cultures
o Criticized as artifact of Western culture

Rat Sexual Behavior


- Female rat must first be sexually receptive
o In heat
- Females do not have menstrual cycle, but an estrous cycle
o Ovulating and interested in amle
o Every 4 or 5 days capable of conceiving
o Rabbits: ovulate in response to sex act
o Under hormonal control: estradiol (is estradiol in humans or just
rats?)
An estrogen
Ovarectomy: remove main source of estradiol, no interest
But can make her sexually receptive whenever you wish via
(estradiol/progesterone injections)
- Male:
o Testosterone
o Castration: removal of testes, no testosterone, not interested

Rat Sexual Behavior


- Very sterotyped, largely innate
o Dependent on circulating blood levels of sex hormones
o Triggered by stimuli coming from both animals
- Female is originally though to be very passive
- But 70s showed female rat also showed interest
- Females:
o Hop/dart, attracts males
o Also do ear wiggle, so fast must videotape by high speed
o Also nuzzles
o May also be doing ultrasonic calls
o Followed by lordosis posture
- Males:
o Sniffs rear end (anogenital sniffing)
o Then mounting and intromission (penil insertion into vagina)
Female assumes lordosis posture, freezes as reflex

MPOA
- Male sexual behavior in rats is dependent on the activity of the medial
preoptic area (MPOA)
- All of this is dependent on the medial preoptic area (MPOA)
o Called preoptic because it sits below optic chiasm
o Contains neurons that hae receptors for testosterone
On cell membrane
Rapid transmission if testosterone bidns
Also in nucleus
Activates certain genes, slower
Tesosterone is a steroid hormone
- Testosterone:
o Why do athletes take testosterone/steroid?
Puberty: hair, bulking up of muscles
Baseball: homerun era, barry bonds
Lot of other hormoens that are steroids
Just that testosterone has been tagged as steroid by
media
o If you inject a castrated male rat with testosterone he will not
immediately be ready
Must wait 24 hours
Activation of genes/transcription/translation, all of that takes
time
o Same story for female:
If you ovarectomize her, then inject with estradiol/progesterone
It will take at least 24 hours for her to be interested.
- MPOA neurons respond to both olfactory and somatosensory sex-
related stimuli; circulating testosterone sets their responsivity to
the stimuli
o Vomeronasal organ:
Organ in the nose, humans have it to, detects pheremones
Pheremones: chemicals used for social signaling
women in college dorms, periods all synchronize (didnt
hold up)
o Vomeronasal organ projects to the medial amygdala
o Medial amygdala project to the mPOA
o mPOA projects down to the brainstem
o At numerous points along this route, neural sensitivity is adjusted by
testosterone
Amygdala, mPOA, even down in the spinal cord
Same thing with female, even if hormone is different

Circuitry
- Olfactory stimuli reach the MPOA via a relay in the Medial Amygdala;
somatosensory stimuli reach the MPOA via a relay in the Central Tegmental
Field
- mPOA
o Lesioning of mPOA abolishes sexual behavior
Can give rat as much testosterone as you want, wont have
interest in female
Japanese culture: destroys mPOA as punishment for rapists
o Electrical stimulation of the mPOA turns on sexual behavior
o Sacing male rat after sexual behavior results in high Fos expression
o Cannular injection of testosterone into mPOA of castrated male rats
results in resurgence of sexual behavior
o Receives inputs from central tegmental field and olfactory bulb
o You smell her, you feel her, you have testosterone = good to go
All rather programmed and reflexive
- Medial Amygdala
o Lesioning medial amygdala disrupts (DOES NOT DESTROY) sexual
behavior
o Mating causes production of Fos protein (just like mPOA)
- Central tegmental Field of Midbrain
o Receives tactile information coming from genitals
o Mating causes production of Fos protein
o Projects to Medial Amygdala and mPOA

David Edwards
- Showed overlap of neurons taking up testosterone and activated by sexual
behavior
o Killed male rats right after sexual activity stain for Fos
- Overlap in:
1. Bed Nucleus of the Stria Terminalis (BNST)
2. Medial Amygdala
3. Tegmentum
- Stained for Fos and testosterone uptake
o Left: where testosterone was accumulating
o Right: where neurons were being turned on (Fos)
- mPOA, BNST, medial amygdala
o Many more neurons take up testosterone than display Fos, what does
this mean?
o There are neurons in these areas that take up testosterone but ARE
NOT turned on by sexual behavior
o Most likely aggression

Ventromedial Hypothalamus/Nucleus (VMH/VMN)


- Female sexual behavior in rats is dependent on the activity of neurons in the
Ventromedial Nucleus of the Hypothalamus (VMH or VMN)
o Not as complex
- Ventromedial hypothalamus (VMN = ventromedial nucleus)
- VMH/VMN sends axons downt to area around acqueduct, part of the
ventricular system
o Periacqueductal gray: collection of neuronal nuclei around cerebral
acqueduct (connects 3rd and 4th ventricles)
o PAG projects down to medullary reticular formation
- MRF projects down to spinal cord
- Estrogen is what sensitizes these neurons (NOT testosterone which is for
males)
o Olfactory info comes in, goes to medial amygdala, goes to VMH (not
mPOA)
o In males mPOA is important for aggression and sex
o In females mPOA is not involved in sexual behavior, but maternal
behavior
- Ventormedial Hypothalamus
o Destruction of VMH abolishes sexual behavior
o Karate chops male if he tries to mate, even if you load them up with
estradiol
o Question: is it because they have no interest or because made them
more irritable? Can you give them a drug to make them more
receptive?
Tranquilizing drugs didnt help, but amphteamines did???
Its for sure not that they become irritable, but that it removes
their interest
o Mating causes Fos production
o Injection of estradiol/progesterone to ovariectomized rats induces
sexual behavior
o Stimulation does not produce sexual behavior!!!!!
Some axons that run through VMH, causes females to become
extremely angry
Gender Bending (for Rats)
- The rat brain begins as a female, even in genetically male rats.
- Exposure to testosterone soon after birth in the male masculinizes his brain
(rewires it to the male form).
- The testosterone is converted in the brain into estradiol, which does the
masculinization in the male. The female is protected from masculinization by
-feto-protein, which binds to estradiol (not testosterone) in the blood
Experimental Data
- Males - > female:
o castrate a male rat within a few days of birth
o brain will remain female
o show female behavioral characteristics when adult.
- Female -> male:
o inject a female rat with testosterone or estradiol within a few days of
birth
o brain is masculinized
o show male behavioral characteristics when adult.
- None of the above happens if you do the manipulations in the normal adult
rat.
o Organizational effect: The ability of hormones to modify the brain in
the neonate is.
o Activational effect: The ability of hormones to engender sexual
behavior in the adult

Gender Bending
- Pastor protection act: people wont have to perform marriage ceremonies
that dont align with their beliefs
- Basic mammalian brian is though to be originally female
Gender Bending:
- Masculinization: brain rewired into male version of brain
o Exposure to his own testosterone
- Consequences:
o Human: exposure in utero, our gestation is much longer
o Rat: shortly after he is born
o Theres a chance for things to go awry, not just with thiings concerned
with sex
- In male:
o Brain is converted to estradiol in brian
o The female sex hormone is actually responsible for masculinization
- In females:
o How do baby females stay with female brains?
o All get bathed in estrogen from mom, so how can there be female
brains beyond birth?
o Why doesnt female rat become maculanized by estradiol from in
utero?
- Both male and female rats have alpha-feto protein in blood in utero
o binds to estradiol
o Alpha-feto protein grab estradiol so female doesnt get masculinized,
- So then how does male get masculinized?
o Estradiol does not enter his brain because grabbed by alpha-feto
o Testosterone, however, is free to enter
o Alpha-feto protein does not stop testosterone from working, binds to
estradiol
o Doesnt bind to estradiol in the brain due to the BBB
Too big
Testosterone can enter though

In Rats:
- SDN developes in response to estradiol, suppresses female systems
- Lesioning SDN, adding estradiol causes lordosis posture in males
o In adults, when brain has already been masculinized
- Male:
o Simply castrate after birth
o Brain gets femenized
- Female:
o Inject with testosterone or a lot of estradiol (so it overwhelms alpha
feto protein)
o Brain gets masculanized
- But there is an optimum window to do this
o After two weeks there will be no effect
- Organizational effect:
o Brain is in window, shortly after the birth (in humans in utero)
o Rewiring of the brain, once after you can fool however you want but
you wont change the brain structure
o Effects brain anatomy
- Activational effect:
o Not interested in sex, but brain structure remains the same
o Effects sexual behavior

Shah 2004
- Sexual dimorphism in testosterone receptors in the medial preoptic
of mice
- Looks at medial preoptic area (MPOA)
- Used a Nissl stain:
o Nissl bodies are in neurons, endoplasmic reticulum
o Nissl stains ERs purple
- Only males have densely stained area
o Called SDN (sexually dimorphic nucleus) in MPOA
- Larger in males than in females
- If you castrate a male rat a few days after his born
o Looks like female, no SDN stained
o SDN is small
- If you take female rat, inject testosterone/lot of estradiol
o Looks like male
o SDN is large
- How does male sexual behavior dominate over femal behavior is males have
VMH?
o Female rat:

VMH is crucial for female sexual behavior
o Male rate:
Has VMH too, but doesnt show female sexual behavior, why?
SDN inhibits
o How to make femal behavior pop out?
Lesion SDN
Administration of estradiol results in lordosis
o Female systems is still present, just suppressed by male system

In People:
- In rodents
o Exposre of female to high dose of estradiol immediately after birth will
masculinize her brian
o This is not seen in humans, masculinization is done by testosterone
- 2 differences in humans:
o 1. effect in humans is thought to be in utero
o 2. estrogen does not masculinize, only testosterone does
Rodent perculiarity
- Basic brain is female, and if you dont do anything, it stays that way
o If you expose it in the rat to testosterone or estradiol (a high dose),
both of those will masculinize the brain
In rats there is a window of time, after birth, for this to be done
o In humans, this effect is not after being born, it is IN UTERO
Also it is only TESTOSTERONE that masculinizes the brain
Estradiol does not do anything
The window of plasticity is in utero
- Literature in humans is in bits and pieces, general consensus is that yea stuff
is going on in people too
o But not as much work in rats, why?
In rats you do experiments, administer hormones/castrate
o Cannot do in humans, must go by medical phenomenon or things that
happen in nature
Chung 2002
- Sex-related brain difference in humans: adult increase in volume of
the bed nucleus of the stria terminalis in males, not in females
- Looked at bed nucleus of the stria terminalis, BSTc (not MPOA, which we know
to be important in male sexual behavior)
o 14 and 39 year old humans
- Stained for vasoactive intestinal peptide (VIP) and somatostatin (SOM)
o Neuropeptides that are NTs
- Just looking for sex differences in the brain
- Showed that BNST increased in size with age IN MALES, but not in females
- BNST has been related to sexual orientations and responsivity to stress
o Small BNST in females might have something to do with higher
occurrence of depression
Neuroanatomy and Sexual Orientation
- Sexual orientation can be defined in 3 ways
o 1. behavioral
With whom do you have sex?
o 2. self identification
How do you view yourself?
o 3. dispositional view
With whom would you have sex?
- Sexual orientation is not a voluntary choice
o Seems to be a biological predisposition

Experiments in Nature/Acciedents
- Congenital Adrenal Hyperplasia
o experiments of nature
o CAH: congenital adrenal hyperplasia
Fetuss adrenal gland does not produce hormone cortisol
Instead produces masculinizing androgens
o Fetus gets exposed IN UTERO to higher level of androgens than usual
Females born may have ambiguous genitalia
Females will also have higher levels of gender dysphoria
o Gender dysphoria: not happy with gender assigned to them (culture)
Plays more with boy toys
o Females monkeys will still play with dolls, boy monkeys will play with
wheels
Appears to be something heavily biological
o CAH women will more likely be attracted to women and identify as
homosexuals
o Money 1984: 37% of CAH
- Synthetic Estrogens:
o Women given hormone to suppress miscarriage (DES)
DES: diethyl sebestrol, synthetic estrogen
o Partially masculinized brain
More likely to feel same-sex attraction than unexposed sisters
o But you said estrogen doesnt masculinize human brain? Only
in rodents.
Weird peculiarity

Swaab 1989
- The area of the SDN, known as INAH-1, has been found larger in men
than women
- Looked at SDN (in humans known as INAH-1)
o Counted cell number,
- Males had greater cell number throughout life
Simon Levay 1991
- INAH3 cell group of SDN area dimorphic differences in homosexual
and heterosexual males, suggesting INAH-3 might be human analog
of SDN
- INAH3: third interstitial nucleus of the anterior hypothalamus
o Larger in straight male vs. straight female
o Larger in straight male vs. gay male
- AIDs epidemic in San Francisco, got the brains of gay men died from AIDS
- Main weaknesses:
o 1. whether AIDS virus changes the brain
o 2. assumed that if a man died from AIDS he was most likely gay
- Claimed INAH-3 (NOT INAH-1, proposed by schwabb) was the human analog
for the SDN
o Larger in males than heterosexual females and homosexual men
- Cell clusters in INAH-3:
o 3rd interstitial nucleus of the anterior hypothalamus
o Suggesting that INAH-3 is the human version of the SDN
o INAH-3 is larger in straight man than straight woman or gay man
- Promoted the idea that prenatal underexposure or overexposure to fetal
androgens cause gay mens brains to be feminized and lesbian brains to
be masculinized
Swaab 2008
- Volumer and numbers of neurons in INAH-3 are smaller in females
and male-female transsexuals than heterosexual males
- Other study also done on INAH-3 in transsexuals
o Counted volume and number of neurons
- Swaab did additional study, now on INAH-3
o Found size of INAH-3 to be small in heterosexual female and male-
female transsexuals
o However, homosexuals are not the same as male-female transsexuals
o Not all homosexuals are effeminate!

Other Areas
- Swaab 1990
o Suprechiasmatic nucleus (SCN) is two times larger in
homosexual males than in heterosexual males
o SCN another area that shows size difference between homosexual and
heterosexual males
Swaab AGAIN 1990
Supra = above optic chiasm
Two times larger in homosexual males than heterosexual males
- Allan and Gorski 1992
o Larger anterior comissure in women than men, and larger
anterior comisure in homosexual men than heterosexual men
Limitations
- All research was done in the 90s
o Not sort of thing people look at in terms of career
- Small sample sizes
o Do they accurately reflect the groups?
- How do they define sexual orientation?
o Evidence suggests biology but no 100% sure

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