Sex Differences in Behavior PDF

Sex Differences in Behavior CHAPTER 4 Spine density and size in the female mouse brain compared to the male. Red displays a higher spine density in females, blue a lower one, and green similar levels in males and females. The depiction of the mouse brain is modified from the Allen Mouse Brain At...

Sex Differences in Behavior CHAPTER 4 Spine density and size in the female mouse brain compared to the male. Red displays a higher spine density in females, blue a lower one, and green similar levels in males and females. The depiction of the mouse brain is modified from the Allen Mouse Brain Atlas (2004), Lein et al. (2007). Hormonal Influence on Brain Development Hormones play a crucial role in sculpting and fine-tuning the developing brain. They may influence brain structure and function, leading to observable sex differences in behavior. Possible mechanisms include: Neuronal survival: Hormones can promote or protect against cell death. Neural connectivity: Hormones may influence dendritic branching, axonal projections, and synapse formation. Receptor distribution: Hormones can alter the number and distribution of hormone receptors in specific brain regions. Neurochemistry: Hormones may change neurotransmitter levels and synaptic activity.  Volumetric differences: Types of Refers to size differences in specific brain regions or neuronal cell clusters (nuclei). Sex Some brain areas are larger in males, while others are larger in females. Differen Connective differences: Refers to differences in the type or number of synapses or the size of neuronal ces in projections. These differences influence communication between brain regions. the Implications for Behavior Structural differences in neuronal survival, Brain connectivity, and neurochemistry can lead to functional differences in cognition and behavior. Hormone-driven neural development may contribute to sex differences in learning, memory, emotional regulation, and social behaviors.  Sex and Gender Differences in Brain Zelco, Aura & Wapeesittipan, Pattama & Joshi, Anagha. (2023). Insights into Sex and Gender Differences in Brain and Psychopathologies Using Big Data. Life. 13. 1676. 10.3390/life13081676. Discovery of Sex Differences in the MPOA The first observed sexual dimorphism in the brain was found in synaptic organization in the medial preoptic area (MPOA) of rats. The MPOA is located just anterior to the hypothalamus and is known to regulate sexual behavior. Researchers counted synapses in the MPOA after cutting axonal projections from the stria terminalis. Key Findings Males had more synapses on dendritic shafts and fewer on dendritic spines. Females had more synapses on dendritic spines and fewer on dendritic shafts. Hormonal manipulation during early development can alter synaptic organization: Castrated male rats (at day 1) developed a female-like synaptic pattern. Female rats injected with testosterone (before day 4) developed a male- like synaptic pattern.  Possible Implications Male-Typical MPOA (More Female-Typical MPOA Feature Shaft Synapses) (More Spine Synapses) Stronger drive for Greater flexibility in sexual copulation; more direct, Sexual Behavior receptivity; estrogen and testosterone-driven progesterone modulation responses Reduced maternal behavior; Enhanced maternal care; Parental Behavior less responsiveness to increased plasticity in offspring response to offspring cues More rigid, goal-directed More plasticity in response Social Behavior responses (e.g., dominance, to social cues; greater social mating) bonding potential  Not Just the MPOA Males (More Shaft Synapses Females (More Spine Synapses Brain Region Example & Reference – Stability) – Plasticity) More stable synaptic Shahrokh et al. (2010) - Oxytocin- More plastic synaptic connections; Medial Preoptic Area connections; supports male- induced MPOA synaptic changes supports maternal behavior and (MPOA) typical social and sexual drive maternal care. Hormones and hormonal regulation. behavior. Behavior (DOI) More stable synapses; better at More dynamic synaptic Woolley & McEwen (1993) - Estradiol Hippocampus (Memory & habitual spatial navigation connections; better at cognitive increases hippocampal dendritic Learning) and long-term memory flexibility and adapting to new spine density. Journal of Neuroscience consolidation. learning strategies. (DOI) More resilient to acute More sensitive to stress, but Prefrontal Cortex Shansky et al. (2009) - Stress-induced stress, but vulnerable to better at long-term adaptation (Decision-Making & spine remodeling in females. chronic stress (loss of spines (higher stress-induced synaptic Stress Regulation) Cerebral Cortex (DOI) in prolonged stress). remodeling). More stable emotional More sensitive to fear and Cooke et al. (2007) - Sex differences Amygdala (Emotion & responses; better at short- emotional learning; linked to in amygdala synaptic structure. Fear Processing) term fear extinction. higher PTSD susceptibility. Journal of Neuroscience (DOI) More stable dopamine Higher dopamine sensitivity, Becker & Chartoff (2019) - Sex Striatum (Reward & responses, supporting goal- increasing vulnerability to differences in addiction via Motivation – Impulse directed behavior and habit addiction and reward-driven dopamine and synaptic plasticity. Control & Addiction) formation. behaviors. Neuropsychopharmacology (DOI) Functional Significance of the SDN-POA Definition & Location The sexually dimorphic nucleus of the preoptic area (SDN-POA) is a brain structure within the hypothalamus. Larger in males than females due to early testosterone exposure. Lesion Studies & Behavioral Effects Entire POA lesions disrupt normal mating behavior in rodents and primates. SDN-POA lesions (isolated): Females: Normal reproductive cycles continue. Males: Minor or temporary disruptions in copulatory behavior. Hypothesis on Function Initially thought to facilitate masculine behavior. Emerging evidence suggests it may inhibit female sexual behavior in males. The Bilateral Sexually Dimorphic Nucleus of the Preoptic Area SDN-POA, Hormones, & Sexual Behavior Key Findings from Research Entire POA lesions lead to female-typical sexual behavior in males given estrogen and progesterone. Reduction of steroid receptor coactivator-1 (SRC-1) → smaller SDN-POA & increased female-typical behavior in males. Supports the idea that SDN-POA may suppress female-typical behavior rather than actively drive male-typical behavior. Sexual Dimorphism in Brain Structures Key Sexually SDN-POA: ♂ > ♀ (regulated by early testosterone exposure). Dimorphic Medial Amygdala & BNST: ♂ ~20% larger than ♀. AVPV (Anteroventral Periventricular Nucleus): ♀ > Brain ♂ (regulates ovulation). Corpus Callosum (posterior portion): ♂ > ♀ (more Structures bulbous in ♀). Apoptosis & Testosterone prevents cell death (apoptosis) in SDN- POA but promotes apoptosis in AVPV. Hormonal Suggests different genetic and molecular mechanisms in different brain regions. Regulation Sexual Brain Dimorphisms Sex Differences in Brain Morphology & Connectivity Volumetric Differences Differences in brain size relative to body size. Males: Larger medial amygdala, BNST, SDN-POA. Females: Larger AVPV (OVULATION). Connective Differences Males: More synapses on dendritic shafts in MPOA. Females: More synapses on dendritic spines in MPOA. Differences in synapse type suggest different information processing styles. Human Brain Dimorphisms Structural Sex Differences in Humans Hypothalamus: SDN-POA, INAH-3, BNST ♂ > ♀. SCN: More elongated in females. Spinal Cord: Onuf’s nucleus (motor neurons) ♂ > ♀. Language-Related Areas: Planum temporale, dorsolateral prefrontal cortex ♂ > ♀. Corpus Callosum & Connectivity: Posterior corpus callosum ♂ > ♀, but more bulbous in females. More cortical folding in females (higher surface area). Implications Differences in structure do not always imply functional superiority. Sex differences in brain morphology may relate to behavior, cognition, and social processing. Molecular Sex Differences in the Brain  Differences in neural estrogen and androgen receptors may explain sex differences in sexual Sex Steroid behavior. Receptors Early studies found no differences in steroid hormone binding sites, but recent studies and Their reveal modest sex differences. Distribution Sex steroid hormone receptors are highly concentrated in the hypothalamus and parts of the limbic system. Significant overlap exists among neurons expressing: Androgen receptors Estrogen receptors (ERα and ERβ) Progesterone receptors  Males have higher androgen receptor binding and mRNA Regional expression in: Differenc Medial amygdala Bed nucleus of the stria terminalis es in Sex (BNST) Preoptic periventricular nucleus Steroid Ventromedial nucleus of the Receptor hypothalamus Females have higher estrogen and s progesterone receptor expression in: Preoptic periventricular nucleus Medial preoptic nucleus Ventromedial nucleus Summary of Figure 4.9 Overlap of Sex Steroid Receptors: The figure illustrates significant overlap among androgen, α estrogen, and progestin receptors in the rat brain. Brain Regions: Cross-sectional images highlight receptor distribution in various brain areas, including the hypothalamus, amygdala, hippocampus, and septum. Androgen Receptors (A): Indicated by dark spots in specific brain regions. α Estrogen Receptors (B): Marked locations where α estrogen receptors are prevalent. Progestin Receptors (C): Shows areas enriched with progestin receptors. Key Structures: Labels include the anterior commissure, arcuate nucleus, corpus callosum, and periventricular nucleus, among others. Abbreviation Full Name ac Anterior commissure ARH Arcuate nucleus AVPv Anteroventral periventricular nucleus BSTad Anterodorsal nucleus of the bed nucleus of the stria terminalis (BNST) BSTe Encapsulated nucleus of the BNST CA1/CA3 Fields of the hippocampus cc Corpus callosum COAa Cortical nucleus of the amygdala (anterior) COApo Cortical nucleus of the amygdala (posterior) CP Caudoputamen DMH Dorsomedial hypothalamic nucleus EP Endopiriform nucleus LA Lateral nucleus of the amygdala LH Lateral habenula LSv Lateral septal nucleus (lateral part) MAPO Magnocellular preoptic nucleus och Optic chiasm PAG Periaqueductal gray PIR Piriform cortex PS Parastrial nucleus PVp Posterior periventricular nucleus SFO Subfornical organ TU Tuberal nucleus V3 Third ventricle Regulatio n of Sex Sex steroid receptor gene expression is Steroid influenced by circulating hormones. Receptors Testosterone effects: Up-regulates androgen receptors in the medial amygdala. Down-regulates androgen receptors in the medial preoptic nucleus.  Sex differences exist in the Sex distribution and regulation of neurotransmitters. Differences in Dopamine system in the AVPV (anteroventral periventricular Neurotransmi nucleus): More dopamine-containing tter Systems neurons in females than males. No difference at birth, but testosterone/estrogen reduces dopamine neurons in males by postnatal day 10. Sex difference results from the organizational effects of estrogens. Kisspeptin and GnRH Regulation Kisspeptin-expressing neurons in the AVPV regulate GnRH secretion. Females have ~10x more kisspeptin neurons than males. In rats, male AVPV has virtually no kisspeptin neurons. Kisspeptin likely mediates estrogen-induced LH surges. Sexual dimorphism in kisspeptin neurons in AVPV of rats  Males have 2–3x more vasopressin-expressing neurons Vasopress than females in: in and BNST Medial amygdala Sex Vasopressin may regulate: Differenc Male sexual behavior es in Aggression (castration reduces vasopressin and aggression; Social vasopressin injection increases aggression). Behavior Vasopressin inhibits lordosis in female rats, potentially contributing to male sexual behavior patterns.  Arginine vasotocin (AVT), a vasopressin-related peptide, influences behavior in bullfrogs: Only males produce mate calls; AVT increases vocalization. AVT increases female phonotaxis (movement toward calls). Both sexes emit release calls when mounted inappropriately. Vasopressin and Sexually Dimorphic Behavior in Amphibians Sex differences in bullfrog brains mediate calling behavior (A) A male bullfrog. Calling behavior attracts potential mates and wards off competing males. Immunocytochemistry reveals smaller numbers of neuronal cell bodies and fibers containing arginine vasotocin (AVT) in the preoptic area of a female bullfrog brain (B) than in the same region of a male brain (C).  Aggression in mammals is often mediated by serotonin. There are 14+ types of serotonin Serotoni receptors in mammals. n and 3-4 serotonin receptors modulate Aggressi aggressive behavior. PET studies show: on in Higher type 2 serotonin receptors in Mammals men. Higher serotonin 1A receptor binding in women. The role of sex steroids in serotonin/vasopressin receptor distribution is still unknown.  Testosterone acts as a prohormone for estradiol or DHT. Testoster Identifying testosterone receptors and enzymes (e.g., aromatase, 5α/5β-reductase) helps study sex differences. one and Brain regions with high aromatase activity in males: Sex BNST (bed nucleus of the stria terminalis) Medial preoptic nucleus Difference Ventromedial nucleus (VMN) of the hypothalamus s in Aromatase activity is 2-4 times higher in males than females in these regions. Neural Testosterone & DHT (not estrogens) maintain aromatase Tissue activity in certain brain areas. Amygdala shows no sex differences in aromatase activity or mRNA expression.  Epigenetic regulation is crucial for brain sexual differentiation during development. DNA methylation & histone modifications Epigenetics show sex differences in adults. Early-life hormone exposure impacts DNA and Brain methylation of sex steroid receptors. Key findings in rats: Sexual Males exhibit higher ERα promoter methylation than females. Differentiat ~1000 genes are differentially methylated in the BNST & POA. ion 248 genes/loci show differential histone modification. Neonatal testosterone exposure masculinizes methylation patterns. Gene expression differences may only appear when brain circuits are activated for sex- specific behaviors. Epigenetic sex differences Sex differences in the methylation of the ERα promoter are observed in rats and may account for differences in gene expression.