1
Q
For past 50 years, the prevailing view of
sex differentiation of the brain has been a
A
linear model
2
Q
Iconic model based on the
A
organizational/activational hypothesis
3
Q
Linear Model - Sex order
A
Chromosomal sex determines gonadal sex,
which determines brain sex
4
Q
Feminization of the brain is the
A
default process
5
Q
Occurs in the absence of high levels of
A
gonadal steroids
6
Q
during a
A
perinatal sensitive period
7
Q
Masculinization and defeminization are
A
separate
hormonally driven processes
8
Q
Organize the neural substrate to promote
A
male-typic
behaviours while suppressing female-typic behaviours
9
Q
Which is activated by adult gonadal steroids and required for
A
sex-typic behaviours to be expressed
10
Q
This model has provided a good framework for
A
elucidating some, but not all, of the aspects of
sexual differentiation of the brain
11
Q
Four Core Genotypes Model
* Mouse model that advanced understanding of
contributing role of
A
genes vs. gonads
12
Q
Some mice contain a Y chromosome from
which the SRY gene has been
A
deleted
13
Q
Denoted as?
A
Y−
14
Q
Others carry SRY on an
A
autosome
15
Q
Any chromosome that is not a
A
sex chromosome
16
Q
This allows for the development of: (2)
A
– XX individuals with testes
– XY individuals with ovaries
17
Q
Analysis of this model supports the view
that sexual differentiation of reproductive
endpoints is largely driven by
A
T
18
Q
Or estradiol synthesized from this
A
T
19
Q
Consistent with the
A
organizational/activational hypothesis
20
Q
Conversely, many nonreproductive
endpoints involve direct genetic
contributions to
A
variability between
males and females
21
Q
Two-Stage Model
* Exposure to androgens during the perinatal
and peripubertal periods act in concert to
affect
A
mating behaviour in adult hamsters
22
Q
Given the substantial programming of adult
behaviour during puberty, it has been suggested
that the organizational temporal window should be
A
extended to the peripubertal period
– Around the time of puberty
23
Q
Sex differences in the brain that might be involved
in behavioural sex differences can be broadly
categorized as either:
A
- Connective sex differences
- Volumetric sex differences
24
Q
Connective sex differences
A
Refer to the type or number of synapses or the size of a particular type of projection within the brain
25
Volumetric sex differences
Refer to the size differences in the brains, specific brain regions or collections of neural cell bodies (nuclei)
26
A good place to start looking for sex differences in the brain?
Areas that are known to play a role in sex differences
in sexual behaviour
27
Medial Preoptic Area (mPOA)
Subdivision of the:
anterior hypothalamus
28
Implicated in the control of
homeostatic processes
and motivational behaviours
29
Including sexual behaviour and
gonadotropin secretion
30
Region where neurosecretory cells produce
GnRH
31
Lesions/stimulation of mPOA alter
sexual behaviour
32
The first (1970) clear-cut sexual dimorphism found in the brain was a
connective sex difference
33
Using electron
microscopic examination
34
Dendritic spines have become the focus of much research because
their number and function may
vary in response to experience
35
Especially on
learning and memory
36
Medial Preoptic Area (mPOA)
FEMALES
more synapses on dendritic spines and
less on dendritic shafts than males
37
Medial Preoptic Area (mPOA) MALES
more synapses on dendritic shafts than on
spines
38
Interestingly, hormone manipulations
immediately
postpartum can affect this
pattern of neuronal connectivity
39
Sexually Dimorphic Nucleus of the POA
Volumetric sex differences in the
brain have also been found
40
Sexually Dimorphic Nucleus of the Preoptic Area (SDN-POA)
larger in
MALES
41
Part of the
mPOA
42
Lesions limited to the SDN-POA of rats
result in only subtle
decrements in male
copulatory behaviour
43
But may more consistently disrupt
maletypical partner preference
44
Male and female rats born with similar
number of
neurons in SDN-POA
45
The sex difference in size of nucleus is due to
↓ number of cells in female SDN-POA
46
So what might T be doing here?
T is inhibiting apoptosis (programmed cell death)
47
Although tempting to think that larger =
facilitation of masculine behaviour
48
Instead evidence suggests that larger = inhibition of
female sexual behaviour (defeminization)
49
SDN-POA is larger in males because of T secretion during
perinatal sensitive period
50
Afterwards, T has no effect on
SDN-POA volume
51
Volume of posterodorsal medial amygdala (MePD) continues to respond to
T throughout life
52
About 1.5X larger in
males than females
53
Interstitial nuclei of the anterior
hypothalamus (INAH)
These nuclei in humans are seen in
the same part of the hypothalamus
where the
SDN-POA
is found in rats
54
Interstitial nuclei of the anterior
hypothalamus (INAH)
– INAH-3 is larger in
males than females
55
And larger in straight
men than gay men
56
Anteroventral
periventricular nucleus
(AVPV) is larger in
females
57
Another what difference?
volumetric sex
58
AVPV known to be involved
in regulation of
ovulation
59
Acts as “surge centres” of the
HYP along with
SCN resulting
in cyclic hormonal release
60
Sexual dimorphism in AVPV
kisspeptin neurons
61
Female mice have about
10X more kisspeptin neurons
in the AVPV than males
62
In rats the sex difference is even more
exaggerated
63
as virtually no kisspeptin neurons are found in
males AVPV
64
Early androgen exposure must be inducing
certain changes in these regions
65
Either number of kisspeptin neurons or receptors for
androgens in these regions
66
Kisspeptin in AVPV leads to the release of
GnRH
from HYP
67
Kisspeptin neurons in AVPV have
estrogen
receptors
68
receive
SCN input
69
and are activated
concomitantly with
GnRH/LH surge
70
Provides strong evidence that these cells integrate
estrogenic and circadian signalling to time the LH surge and ovulation
71
Average sex differences often reflect
significant
overlap between the sexes
72
Often see greater differences
between individuals of the
same sex versus individuals
of the opposite sex
73
For behaviour, brain
morphology and
function
74
Men and women use different parts of
their brains to perform different tasks
e.g., to solve navigation and language tasks
75
Male activity
during a rhyming
task is restricted to
left inferior frontal gyrus
76
Females show
activity in both the
left and right
inferior frontal gyri
77
pattern of
activation is more
diffuse
78
21st century view of sexual differentiation
of the brain MODEL
Parallel-Interactive Model
79
Incorporates the importance of
genetics and environment along with the effects of hormones
80
Provides a more nuanced portrayal of
the types of
variables that cause sex differences
81
Hormones, sex chromosome genes, and sexspecific environments have
independent parallel
differentiating effects
82
But these can interact with each other, often BLANK, to cause WHAT?
synergistically, to cause sex differences in the brain
83
There are also compensatory sex-specific
variables that act to
reduce sex differences
rather than induce them
84
Ultimate effect of Xist:
only one X chromosome is
transcriptionally active in females
85
* Xist is typically viewed as a factor that makes females more similar to
MALES
86
Result: some aspects of male and female brain,
behaviour, and physiology are
unique from
each other
87
Whereas others are
highly similar
88
Two important aspects of the redefined view are not illustrated here:
1. Sex differences are pervasive throughout the brain
* Not restricted to reproductively relevant neural circuits
2. Variability in the degree to which brain regions are
masculinized or feminized in one individual results in
a mosaic of relative maleness or femaleness
* Thereby greatly increasing the variance between
individuals of the same sex in a population
89
Sex Differences in Play Behaviour
* Little boys generally prefer:
– Rough and tumble games
– Toys such as trucks and balls
90
Little girls generally prefer:
– Such toys as dolls
91
What Might be the Cause?
– Sex differences in toy preference in infants
observed as early as
3 months of age
92
Using eye-tracking to examine
preference
93
Are hormones involved?
Girls diagnosed with CAH tend to play with
masculine toys more often than girls without CAH
94
Presumably, monkeys have no prior
concept of
“boy” or “girl” toys
95
Yet female vervet monkeys preferred
girl-typical toys
* Such as dolls or cooking pots
96
And males preferred
boy-typical toys
Such as cars or balls
97
There were no sex differences in
preference for
gender-neutral toys
Such as picture books or stuffed animals
98
Young rhesus monkeys also showed
similar toy preferences
99
In rhesus monkeys and many other
mammalian species, males engage in more
play behaviour than their female peers
throughout development
100
A larger proportion of male play
behaviour involves
simulated
fighting
101
Goy & Phoenix: conducted series of studies
on rhesus monkeys to further understand
these sex differences in play behaviour
102
Experimental steps:
Pregnant rhesus monkeys injected with
androgens
103
External genitalia of female offspring was
masculinized
104
Compared play behaviours of these
pseudohermaphroditic females with
males and
females from other pregnancies
105
Males engage in these play
behaviours more frequently
than
normal females
106
But pseudohermaphrodites
are intermediate between
males and females
107
This indicates that play
behaviour is masculinized by
early androgen treatment
108
In addition to the
external
genitalia
109
Interestingly, later studies by
Goy (1981) indicated that
not all components of the
sexually dimorphic juvenile
play behaviours were
affected by
prenatal
androgens
110
For example, play initiation
is sexually dimorphic, but:
* While males initiate more
than females
* Androgenized females did not
differ from control females
111
This behavioural sex difference is not due
to altered genitalia
112
A change in the timing of androgen treatment,
juvenile play behaviour can independently alter
hormonal effects on external genitals
113
So masculinization of the external genitalia
is not obligatory for the effects of
prenatal
androgens on sex differences in behaviour
114
And it is not due to
hormonal activational
effects
115
Castration or other postnatal endocrine
manipulation did not affect
the amount of threat, play initiation, rough-and-tumble play,
116
So strictly organizational?
Environment seems to matter, too
117
For these sexually dimorphic behaviours to be
expressed at all, appropriate
social stimulation
had to be present during development
118
Rearing rhesus monkeys in social isolation
prevents expression of
typical pattern of play
behaviour
119
Organization by hormones interacts with
environmental factors to produce normal play behaviours
PSYC 342
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