Sexual differentiation of NS

Sex & Gender:

Sex biological

 Overt anatomical differences that help defining the gender

 Gonadal (testes or ovaries) and chromosomal (XX or XY) differences help define
a man versus a woman

Gender  social and mental states (what you project yourself to be)

 Gender role: Set of behaviors and social mannerism: clothes, toys

 Gender identity: Feeling of belonging to a sex. Not the same as sexual orientation
(erotic response displayed to one or two different sexes)

Role of genes and hormones:

● They determine physical differences between males and females
● XX and XY direct gonadal differentiation in the embryo
● After birth, gonads secrete hormones that help with sexual differentiation

Basis of sexually dimorphic behavior:

● Related to where your NS is throughout development. Where did it stop, what did
it receive from genetic and hormonal material
● Sexual differentiation occurs in response to many factors:
o Genetic sex determination pathway
o Environmental  also plays a role in social experiences, the way you
were raised, culture, etc
o They work through steroid hormone systems
● Anatomical instances of sexual dimorphism:
o Differences in number and size of neurons
o Differences in number and pattern of synapses. Men have a larger number
and size of certain neurons and larger synapses reflecting erectile
functions in both men and women.

Erectile function + Data:

● the lumbar spinal cord of many animals, including humans, contains a sexually
dimorphic motor center, the spinal nucleus of the bulbocavernosus (SNB). Motor
neurons in the SNB innervate the bulbocaver- nosus muscle, which plays an
important part in penile reflexes in males and vaginal movements in females
● controls it in the lumbar spinal cord, have a nucleus  SNB in rats.
● Before birth, male and female have same number of neurons and the size of this
nucleus is the same in both and the innervation of these muscles is equal. Starting
shortly after birth, shrinkage in number and size of neurons and innervation of
bulbocavernosus muscle is seen in females and the adult male has a larger SNB with
more neurons. So the muscle innervated by it is larger in males than in the females.
● SNB motor neuron innervates the levator ani that is involved in copulatory behavior
in animals, also larger in males.

Origin of differences:
● In female: neurons die early and muscle fibers atrophy early in postnatal life
● Specific female cell death accounts for differences
● Perinatal injection of DHT can rescue some of these cells if done to a rat.

Sexual differentiation in SNB and BCN muscle:

● Bulbo muscle carries androgen receptors, when activated by circulating
androgens, keep muscle alive. The muscle sends trophic factors that keep the
nerves alive.
● If you deprive the muscle of androgen (female), muscle fibers atrophy and die and
then the nerve that innervates the muscle will shrink and die. So you end up with
less neurons in Spinal Cord (SC) and shrunken area
● In SC: have differential innervation when it comes to the reproductive system.
Difference is due to innervation that is lacked by males.
● Note: Spinal circuitries innervating the reproductive systems differ between males
and females.

Hypothalamus controls of mating behavior

● The preoptic region and the bed nucleus of the stria terminalis (BNST) contain
more neurons in males than in females.
● Activated during mating in monkey and human (MRI studies)
● Lesions in the BNST result in deficits in sexual behavior in males and disinhibit
the female type sexual receptivity.
● But does the opposite with preoptic lesions.

Environment cues control some sexually dimorphic behaviors:

● Courtship rituals in rats can be triggered by species-specific vocalization, visual
signals, odors, etc.
● Female rat: present with pheromones, which activate a pathway, which makes rat
sexually receptive to males. Not binary.
● Same pheromones sniffed by male rat trigger different pathway, which gives male
either a fight (if male) or mount (if it is a female) response. It is a binary code.
Early experience:
● Will guide “female oriented” behaviors
● Grooming: mother does to the offspring in rats
● Mother that is negligent of offspring versus one that is grooming offspring. The
offspring daughters will do the same. Less licking and grooming with offspring
that were neglected and more with offspring that were groomed by their mothers.

Anatomical brain differences:

● Brain volume in men is larger than in women
● Men’s head is 2% larger
● Early in children: brain size of a boy is 12-20% larger than that of a girl. This
doesn’t affect cognitive ability. Arrangement of matter on inside will compensate.
May affect cognitive ability within same sex

Grey vs. white matter:

● Men have more grey matter than women
● Women have more white matter: more connectivity and association and ability to
multitask.

Correlation with IQ:

● Brain areas and size activation correlated to IQ
● Men and women have similar IQs but brain areas differ
● In males: see great activation in grey matter, mainly the frontal cortex, right
sagittal and Wernicke is activated. Look at parietal area. Little activation of white
matter in males. Men have a good processing area.
● Females: mild activation in frontal cortex and gray matter may be around Broca’s
area.
● Both genders are intelligent but process/work on intelligence differently and
intelligence is not localized to one area of the brain. It is diffused.
o Association= women are smarter.
o Brain activity and consumption of ATP and neurons that work in grey
matter= men are smarter.

Sexual dimorphism in human brain (17&18):

● Brain structures that are larger in males:
o Onuf’s nucleus in the SC, equivalent to the SNB in rats.
o BNST and suprachiasmatic nucleus also in the brain
o Preoptic area: involved in mating behavior. Larger in men than women
with 2x more cells
 Differences also in androgen receptors in various areas.
  Several cortical areas are larger in women: cingulate gyrus and corpus callosum:
helps with connectivity and emotions.
 In males: frontomedial cortex and amygdala and angular gyrus. Amygdala= raw,
rough emotions and fighting.

Functional differences (19-23):

● Based on behavioral studies
● It is a spectrum
● Don’t neglect culture and social atmosphere
● Culture has raised us as two different species. With equality, this frame of
behavior may change and may impact the way brain processes information. So
these studies are based on a population that exists today.
● Men= use left side of brain with language. Bilateral for women. Right side of
brain= emotionality of speech. So with women, both areas are active
● Girls try to study, use a step by step approach to put things together
● These are based on brain studies and observational studies. Functional differences
are mostly based on behavioral studies.
● Stress:
o Increase blood flow in prefrontal cortex in males.
o In women, increase to limbic system.
● Men use abstract concepts whereas women use landmarks.
● Men: more rough and tumble play; women: more nurturing
● Men: more direct aggression (punching, hitting, pushing); women: more indirect
or relational aggression
● Male brain better at visual, spatial abilities, quantitative problem solving, 3D
● Female brain better at verbal memory tasks, verbal fluency tasks and in speed of
articulation.
● Men: more independent, dominant, spatial and mathematical skills, rank related
aggression. Women: show more concern through sad looks, sympathetic tone etc,
and can think logically and emotionally at the same time.

Sexual dimorphism underlie gender identity and sexual orientation:

● Single gene mutations that dissociate anatomical sex from gonadal sex and
chromosomal sex:
o CAH
o CAIS (someone who may be a boy but raised as a girl until they are a
teenager).
 Girls with CAH (fetal exposure to testosterone)  exhibit changes in gender-
related behavior e.g. toy preference; increased incidence of homosexual or
bisexual behavior.
 This shows you that predetermined division is not that predetermined, exposure to
different hormones play a role.
Olfactory activation:
A. Positron emission tomography (PET) imaging was used to identify brain regions that
were activated when subjects sniffed androstadienone (AND) or estratetraenol (EST)
compared to nonodorous air. AND activated several hypothalamic centers in the brains of
heterosexual women but not men, whereas EST activated several hypothalamic centers in
heterosexual males but not females. Patterns of activation in the hypothalamus of
homosexual men were similar to that of heterosexual women in response to AND, while
similar patterns of activation were found in heterosexual men and homosexual women in
response to EST. The color calibration on the right shows the level of putative neural
activity. Because the same brain regions were selected to compare the figure does not
illustrate maximal activation for each condition.

B. Heterosexual and homosexual subjects were scanned
 while breathing unscented air,
and a measure of covariance was used to estimate connectivity among regions. In hetero-
sexual women and homosexual men the left amygdala was strongly connected to the right
amygdala, whereas connectivity remained local in heterosexual men and homosexual
women. Because the same brain regions were selected to compare, the figure does not
illustrate maximal activation for each condition.

o Differential response to smell. May not be pheromonally driven but still

differentially different to stimulus that activate different areas of the brain.
o B: gender neutral smell. Unilateral activation of amygdala in hetero man and
bilateral activation in the hertero woman, resembling the response of
homosexual man. Homosexual woman resembles the heterosexual man!
o That implies a heavy connectivity between amygdala of hetero woman
potential for more emotional response in women than that in the man. So
men respond more aggressively than compassionately because they engage
less brain areas. These differences exist.

Differential responses to thermal stimulation:

● Volunteers perception of psychophysical response within each sex to thermal
stimulus (49 degrees C probe put on ventral aspect of arm to illicit pain)
● Before imaging was done, men and women were asked to assess or rate the pain:
some rated as intense sensitive; while others labeled as mild  low sensitivity
● Huge difference in response:
● A: major activation of cingulated cortex compared to low sensitivity which shows
activation in thalamus and cerebellum (low)
● This pools both sexes together. Psychophysical perception of pain. You can be a
highly sensitive man who responds like a woman or you can be a woman with
low sensitivity who can respond the same way to a low sensitivity man
● So differences still exist if change stimulus
Differential responses to colon distention in healthy humans:

● Assess threshold for visceral sensitivity and study disease of functional and
chronic pain like IBS or IBD (Chronic pains which are very difficult to manage.)

● Put balloon in descending colon and rectum and inflate it to different pressures.
Some are subthreshold for pain and others might be at perception threshold. They
sense something like a filling of their descending colon and rectum, urge to go to
the bathroom.
● Above perception threshold: pain
● Male v female:
o Activate cingulated gyrus in females but not in males.
o In males= parietal response.
So regardless of threshold, some stimuli will show differences in threshold.
 Anatomical differences are there; functional differences are there too. Some are
modifiable while others are constants and fixed.

Susceptibility to disorders:
● Females have higher predisposition to Alzheimer’s disease, addiction, depression,
anxiety etc.
● Studies done in populations where in general the male isn’t the kind who would
complain. Get more responses from female so it skews the response.
● Males: autism more predominant, ADHD, schizophrenia.
● There are drugs for pain, IBS, chronic disorders that cater more to one sex vs. the
other more active in one sex. (Gender specific drugs)
● So you have this wide spectrum, of anatomy, hormones and neural variations that
underlie w wide spectrum of behaviors and susceptibility to disorders.