1. Tues April 5, 2012 Diane Lagace, PhD CMM/BIO4350
Assistant Professor Department of Cellular and Molecular Medicine (CMM) Neuroscience Program RGH, Room 3510G, University of Ottawa,

2. Exam Info QUESTIONS ALL IN ENGLISH CAN ANSWER IN FRENCH OR ENGLISH
INSTRUCTIONS
This is a closed-book exam. No supplemental materials are allowed.
Read each question carefully and answer ALL questions.
The exam will be graded out of a total of 50 marks.
The first section is based on Dr. Beique’s material and is worth 10 marks. This includes questions B1-B3.
The second section is based on Dr. Maler’s material and is worth 10 marks. This includes questions M1-M3.
The third section is based on Dr. Lagace’s material and is worth 30 marks. This includes questions L1-L17.

4. 6 Lectures Sex and the Brain Chapter 17 (p534-561)
Embryonic Development 101
Chapter 7: Understanding CNS structure through development (p )
Gross Neuroantaomy
Chapter 7: Gross Organization of Mammalian Nervous System (p )
Chapter 23 Genesis of Neuron, Connections and Elimination of Cells and Synapses (p
Chapter 7 Appendix: Illustrated Guide to Human Neuroanatomy (p )
The Genesis of the Neuron (Neurogenesis) and Neuronal Connections and Regeneration of Nervous System
Chapter 23: Connections and Elimination of Cells and Synapses (p )
From lecture notes only; not in text book
Chemical Controls of Brain and Behavior
Chapter 15: Hypothalamus, ANS, Neurotransmitter Systems (p )
Motivation and Homeostasis
Chapter 16: Feeding Regulation Short and Long-Term and Why We Eat (p )
Sex and the Brain
Chapter 17 (p )

5. Sex versus gender
The Genetics of Sex: XY or XX, SRY gene
Sex Development and Differentiation
Steroid Hormones: Biosynthesis, Release, Action in Brain (LH, FSH, GnRH)
Neurochemistry of Reproductive Behavior: Prairie Vole, Oxytocin, Vasopressin
Sexual Dimorphisms : Varies Across Species
Sexual Dimorphisms in Cognition in Humans
Activation Effects of Sex Hormones
Testosterone Sexual Activity
Brain Plasticity and Maternal Behavior
Estrogen Effects: Neurite growth, seizure threshold

6. http://www. loyarburok

8. P

9. Genderless – Baby Storm
June 2011

10. Genotype- Male: XY, Female: XX X chromosome larger than Y
The Genetics of Sex
Genotype- Male: XY, Female: XX
X chromosome larger than Y
X contains 1500 and Y contains 50 genes
In humans Dad contributes X or Y to make male or female
X-linked diseases: Occur more often in men than women
p535

11. P297, 535

12. Sex-Determining Region of Y Chromosome (SRY)
Location of SRY on Y chromosome
Encodes testis-determining factor
Causes development of testes and testicular hormones
Makes fetus develop as male
Default pathway, female
p535

13. Sexual Development
First 6 weeks sexually undifferentiated
Uncommitted gonads: 2 ducts
Fetus has Y chromosome and SRY gene, make testosterone then:
Wolffian duct develops into male internal organs
Inhibition of Mullerian duct development by hormone called Mullerian-inhibiting factor
Hermaphroditism: genitals intermediate between male/female P

14. Sex hormones: Steroids made from cholesterolP

15. Steroid Biosynthesis… bit more complex

16. Fetus has Y chromosome and SRY gene, make testosterone
ACTUALLY is testosterone – converted to estradial by aromatase that causes masculinization – careful here p549 bottom)
p549

17. Female concentration testosterone is ~10% of male
Sex Hormones
Female concentration testosterone is ~10% of male
Males: Testes- release androgen
Testosterone – increase at puberty leads to
development of secondary sex characteristics
Females: Ovaries- secrete estradiol (estrogen) and
progesterone (progestin)
Blood concentrations of sex hormones vary
Males- levels fluctuate daily
Females- levels fluctuate, 28-day cycle P

18. Once AGAIN – we look at…….
What regulates the Secretion of Steroid Hormones from Gonads
Once AGAIN – we look at…….
Last lecture
P488, 539

19. All of them together – from what we have learned so far

20. Bidirectional Interaction Between Brain and Gonads
Hypothalamus:
GnRH – gonadotropin-releasing hormone
Gonadotropins:
LH and FSH
Males- LH produces testosterone; FSH aids sperm maturation
Females- LH, FSH cause estrogen secretion
p539

21. Seasonal Variations: GnRH - Melatonin
The light and dark regulation of the biological clock (suprachiasmatic nucleus),
pineal melatonin production, and seasonal reproduction in photoperiodic mammals.
Nonhuman species
Light inhibits melatonin from pineal gland
GnRH inhibited by melatonin
Seasonal change in elevation of melatonin function of calendar
Season of breeding, Adjust gestations lenght
How you get season of breeding: spring;)
The light and dark regulation of the biological clock (suprachiasmatic nucleus), pineal melatonin production, and seasonal reproduction in photoperiodic mammals. Specialized photoreceptive cells in the retinas (melanopsin-containing ganglion cells) mediate the effects of light (450–490 nm) on the biological clock and melatonin production. The circuitous neural connections between the eyes and the pineal gland (pinealocyte) are shown. At night, the postganglionic sympathetic neurons ending in the pineal gland release norepinephrine, which activates primarily β-adrenergic receptors to stimulate a cascade of molecular events that culminate in melatonin production and release. Seasonally changing photoperiods alter the duration of elevated nocturnal melatonin production, a signal that provides mammals with the time-of-year information. This message determines the breeding season of both long-day and short-day breeders. In both cases, the young are characteristically delivered in the spring or early summer. ASMT, acetylserotonin O-methyltransferase; HIOMT, hydroxyindole O-methyltransferase; NAT, alkylamine N-acetyltransferase.
Reiter R J et al. Biol Reprod 2009;81:
p539

22. Feedback to the Brain
p539

23. Aromatase act at ER receptors
Feedback to the Brain
Estradiol –
ER receptors
Testosterone–
Can have 2 actions:
Androgen Receptors
Aromatase act at ER receptors
p539

24. Distribution of Estradial Receptors in Rat Brain

25. Steroid Hormones Get Inside and Act Within Cells: Indirect Effect
Steroid hormones and thyroid hormones, because of their lipid solubility, bind directly to their receptors in the cytoplasm of target cells. Once bound to its receptor, the steroid hormone-receptor complex travels to the nucleus, where the steroid hormone-receptor binds to promoters of genes, either stimulating or repressing transcription.
P538, 549

26. Steroid Hormones Indirect Effect vs Direct Effect on Neurons
They can indirectly influence gene transcription.
Direct:
Steroids can directly affect transmitter synthesis, transmitter release, or postsynaptic transmitter receptors.
p549

27. Hormones Act at Receptors on Extracellular Membrane
Hormones act only on cells that are able to bind to the hormone, based on the presence or absence of receptors for the hormone on the cell membrane.

28. Biosynthesis, Release, and Action of Steroid Hormones
Whole story
Male: Testosterone
p539

29. Neurochemistry of Reproductive Behaviors
p544

30. Meadow vs Prairie Vole: Differ Reproductive Social Behaviors
Although prairie voles and meadow voles are similar in physical appearance, prairie voles are highly affiliative as depicted here in 'huddling' side by side (a), whereas meadow voles are solitary (b). c, d, Partner preference test. After mating and cohabitating with a female, a male prairie vole tended to spend significantly more time in contact with the partner (filled columns) than the stranger (open columns) (P < 0.05, Student's t-test) (c), whereas meadow voles do not form partner preferences and spent relatively little time huddling with either female (d). P
Enhanced partner preference in a promiscuous species by manipulating the expression of a single gene
Miranda M. Lim, Zuoxin Wang, Daniel E. Olazábal, Xianghui Ren, Ernest F. Terwilliger and Larry J. Young
Nature 429, (17 June 2004)
doi: /nature02539

31. Oxytocin and Vasopressin Receptor Expression Differ
Figure 2. Contrasting Distribution of Oxytocin and Vasopressin V1a Receptors to Prairie (Monogamous) and Meadow (Promiscuous) VolesReceptors are labeled with iodinated ligands by in vitro receptor autoradiography. Levels matched across species with arrows pointing to homologous structures. Prairie voles show higher binding in nucleus accumbens for oxytocin and ventral pallidum for vasopressin. Meadow voles show higher binding for vasopressin in lateral septum. Not shown are differences in other regions, including posterior cingulate-retrosplenial cortex (high for vasopressin V1a receptor in prairie vole) and ventral thalamus and amygdala (high for oxytocin receptor in meadow vole). PFC, prefrontal cortex; CP, caudate putamen; NAcc, nucleus accumbens; LS, lateral septum; VP, ventral pallidum. Figure adapted with permission from Hammock and Young (2006). P

32. Altering Vasopressin Receptor Expression
Can Modify Behavior
Oxytocin, Vasopressin, and the Neurogenetics of Sociality
Science 7 November 2008: vol. 322 no P

33. OR NOT? Are there sexual dimorphisms?
HOW AND WHY male and female BRAINS DIFFER
OR NOT?
Are there sexual dimorphisms?
P 546, 547

34. Humans do not have large dimorphisms in gross anatomy
This is not what most people think…. because

35. The claim: Womens’ corpus callosum is larger than mens’ and that difference is important.
4/15/2017 6:56 PM
Women use both sides of their brain more symmetrically than men. The larger corpus callosum in women explains female intuition and the ability to “multitask” and tune in to emotions.
According to Michael Gurian:
March 2006 Parents magazine,
The Daily Telegraph,
Ottawa Citizen,
Cleveland Plain Dealer,
many, many more
MIT Women & Gender Studies Presentation
September 16, 2008

36. The facts: Corpus Callosum.
4/15/2017 6:56 PM
The facts: Corpus Callosum.
Neuroscience and Biobehavioral Review, 1997:
No statistically significant differences in the corpus callosum area between sexes.
Recent studies using MRIs, taking into account such things as differences in brain sizes, do not support any such difference in men and women.
A meta-analysis of 49 studies found no significant sex differences in the size or shape of the corpus callosum. v
MIT Women & Gender Studies Presentation
September 16, 2008

37. Some species do have large dimorphisms in gross anatomy
Can identify male or female by trained eye
P 546, 552
Blue circles are the vocal control regions (VCR) in the male and female zebra finches

38. Sexual dimorphisms another example - THE “SDN”
The sexually dimorphic nucleus (SDN) in hypothalamus of males (left) is larger then females (right)
Lesion SDN disrupt estrous cycle in females, reduce frequency of copulation in males
Newborn rat given estrogen, will have larger SDN, develop masculine behaviors

39. Sexual Dimorphisms in Cognition
Cognitive tasks that may favor women or men. (a) Women may outperform men in listing words beginning with the same letter. (b) Men appear to be somewhat better at spatial rotation tasks, such as deciding whether two three-dimensional objects are the same. (Source: Adapted from Kimura, 1992, p. 120.)
P 548

40. 4/15/2017 6:56 PM
d’ = 0.15
Although the overall gender difference in math was trivial, there were measurable gender differences for complex-problem solving beginning in high school.
The effect size was .29, favoring males.
This difference, it was argued, could forecast the under-representation of women in science, technology, engineering, and mathematics careers.
254 studies, 3,175,188 students
MIT Women & Gender Studies Presentation
September 16, 2008

41. Gender Gap - Math – Influence of Culture
There was similar variation in the proportion of girls and boys who scored above 95% or 99% of the country-level distribution.
GGI = Gender Gap Index
TUR KOR ITA USA PRT FRA POL NOR SWE ISL
Guiso, L., Monte, F., Sapienza, P., & Zingales, L. (2008). Culture, gender and math. Science, 320(5880),
MIT Women & Gender Studies Presentation
September 16, 2008

42. 4/15/2017 6:56 PM
To examine the cultural inputs to these differences, the researchers classified the ten countries by four, highly correlated, measures of gender equity.
These measures assess the economic and political opportunities, education and well-being of women.
The gender gap in mathematics correlates with country measures of gender status within the culture.
More gender-equal cultures are associated with reducing the negative gap in math
These results suggest that the sexual dimorphisms in math ability disappears in more gender-equal societies.
MIT Women & Gender Studies Presentation
September 16, 2008

43. Organizational vs Activation Effects of Steroid Hormones
Organizational effect of hormones
Organizes perinatal tissue
Tend to be irreversible
Allow for development of distinct genitals and behaviors later in life
Activational effect of hormones
Effects occur after early development
Tend to be temporary
4 examples: testosterone role in sexual behavior, effect lactation on sensory representation in cortex, estrogen on neurite growth, fluctuations of hormone and seizure threshold
P550,551

44. Testosterone Men: Rise in testosterone, anticipation of sex,
Fall in testosterone, decreased sexual interest
P555

45. Effects During Nursing
Plasticity in Cortical Regions that Surround Nipples
P555

46. Estrogen – Neurite Growth Dominique Toran-Allerand, 1980s
Estradiol treatment of tissue taken from hypothalamus of newborn mice induces extensive outgrowth
P555

47. Estrogen –Spine Number, Excitability in Hippocampus
Gould, Woolley, and McEwen
Estradiol increases number of spines
More excitatory synapses
More NMDA glutamate receptors
Reduced seizure threshold (see Fig )
P556, 557

48. Hormone Replacement Therapy
Hormone Effects

49. Sex versus gender
The Genetics of Sex: XY or XX, SRY gene
Sex Development and Differentiation
Steroid Hormones: Biosynthesis, Release, Action in Brain (LH, FSH, GnRH)
Neurochemistry of Reproductive Behavior: Praire Vole, Oxytoxin, Vasopressin
Sexual Dimorphisms : Varies Across Species
Sexual Dimorphisms in Cognition in Humans
Activation Effects of Sex Hormones
Brain Plasticity and Maternal Behavior
Estrogen Effects: neurite growth, seizure threshold

50. Example Question
Describe what happened to pair-bonding when vasopressin receptor was expressed into the meadow vole. You can use a graph to help explain your answer if you wish.
2 MARKS
By injecting a virus that allowed increased vasopressin receptor expression into the meadow voles, the meadow vole then preferred to be reproductive with a partner compared to a stranger, like the prairie vole. This suggests that vasopressin receptor expression is important for vole pair-bonding.