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Exam I Study Guide
Exam I Study Guide
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
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
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
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
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?
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
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
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
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