Independent effects of incubation temperature and gonadal sex on the volume and metabolic capacity of brain nuclei in the leopard gecko (Eublepharis macularius), a lizard with temperature-dependent sex determination

The extent to which variation within and between the sexes can be assigned to genes vs. environment is problematic, because, in most vertebrates, males and females differ genetically. However, factors other than sex chromosomes and the consequent sex-typical gonadal hormone secretions may play important roles in the differentiation of the neural mechanisms underlying individual and sex differences in aggressive and sexual behavior. The leopard gecko, like many oviparous reptiles, lacks sex chromosomes. Instead, gonadal sex is determined by temperature during embryogenesis, with low and high incubation temperatures producing females and intermediate temperatures producing mixed sex ratios. In essence, this allows for the study of individual and sex differences without the confounding variable of genetically determined gender. Experiments have shown that the temperature experienced during incubation plays a critical role in establishing the adult morphological, endocrinological, and behavioral phenotype. In this experiment, the independent effects of incubation temperature and gonadal sex on the morphology and metabolic capacity of specific brain nuclei were determined. Both individual and sex differences in the volume of the preoptic area and ventromedial nucleus of the hypothalamus are determined primarily by incubation temperature, not by gonadal sex. However, incubation temperature and gonadal sex are both important in determining the metabolic capacity in the anterior hypothalamus, external amygdala, dorsal lateral nucleus of the hypothalamus, dorsal lateral nucleus of the thalamus, dorsal ventricular ridge, habenula, lateral hypothalamus, nucleus rotundus, nucleus sphericus, periventricular nucleus of the hypothalamus, preoptic area, periventricular nucleus of the preoptic area, septum, striatum, torus semicircularis, and ventromedial nucleus of the hypothalamus. This is the first demonstration in a vertebrate that factors other than gonadal sex hormones, which arise from the individual's genetic constitution, can affect the sexual differentiation of the brain. J. Comp. Neurol. 380:409–421, 1997. © 1997 Wiley-Liss, Inc.     

Distribution of androgen and estrogen receptor mRNA in the brain and reproductive tissues of the leopard gecko, Eublepharis macularius

Incubation temperature during embryonic development determines gonadal sex in the leopard gecko, Eublepharis macularius. In addition, both incubation temperature and gonadal sex influence behavioral responses to androgen and estrogen treatments in adulthood. Although these findings suggest that temperature and sex steroids act upon a common neural substrate to influence behavior, it is unclear where temperature and hormone effects are integrated. To begin to address this question, we identified areas of the leopard gecko brain that express androgen receptor (AR) and estrogen receptor (ER) mRNA. We gonadectomized adult female and male geckos from an incubation temperature that produces a female-biased sex ratio and another temperature that produces a male-biased sex ratio. Females and males from both temperatures were then treated with equivalent levels of various sex steroids. Region-specific patterns of AR mRNA expression and ER mRNA expression were observed upon hybridization of radiolabeled (35S) cRNA probes to thin sections of reproductive tissues (male hemipenes and female oviduct) and brain. Labeling for AR mRNA was very intense in the epithelium, but not within the body, of the male hemipenes. In contrast, expression of ER mRNA was prominent in most of the oviduct but not in the luminal epithelium. Within the brain, labeling for AR mRNA was conspicuous in the anterior olfactory nucleus, the lateral septum, the medial preoptic area, the periventricular preoptic area, the external nucleus of the amygdala, the anterior hypothalamus, the ventromedial hypothalamus, the premammillary nucleus, and the caudal portion of the periventricular nucleus of the hypothalamus. Expression of ER mRNA was sparse in the septum and was prominent in the ventromedial hypothalamus, the caudal portion of the periventricular nucleus of the hypothalamus, and a group of cells near the torus semicircularis. Many of these brain regions have been implicated in the regulation of hormone-dependent, sex-typical reproductive and agonistic behaviors in other vertebrates. Consequently, these nuclei are likely to control such behaviors in the leopard gecko and also are candidate neural substrates for mediating temperature effects on behavior.     

Behavioral correlates of differences in neural metabolic capacity

Cytochrome oxidase is a rate-limiting enzyme in oxidative phosphorylation, the major energy-synthesizing pathway used by the central nervous system, and cytochrome oxidase histochemistry has been extensively utilized to map changes in neural metabolism following experimental manipulations. However, the value of cytochrome oxidase activity in predicting behavior has not been analyzed. We argue that this endeavor is important because genetic composition and embryonic environment can engender differences in baseline neural metabolism in pertinent neural circuits, and these differences could represent differences in the degree to which specific behaviors are ‘primed.’ Here we review our studies in which differences in cytochrome oxidase activity and in behavior were studied in parallel. Using mammalian and reptilian models, we find that embryonic experiences that shape the propensity to display social behaviors also affect cytochrome oxidase activity in limbic brain areas, and elevated cytochrome oxidase activity in preoptic, hypothalamic, and amygdaloid nuclei correlates with heightened aggressive and sexual tendencies. Selective breeding regimes were used to create rodent genetic lines that differ in their susceptibility to display learned helplessness and in behavioral excitability. Differences in cytochrome oxidase activity in areas like the paraventricular hypothalamus, frontal cortex, habenula, septum, and hippocampus correlate with differences in susceptibility to display learned helplessness, and differences in activity in the dentate gyrus and perirhinal and posterior parietal cortex correlate with differences in hyperactivity. Thus, genetic and embryonic manipulations that engender specific behavioral differences produce specific neurometabolic profiles. We propose that knowledge of neurometabolic differences can yield valuable predictions about behavioral phenotype in other systems.     

Projections of the sexually dimorphic calcitonin gene-related peptide neurons of the preoptic area determined by retrograde tracing in the female rat

The medial preoptic area of the rat exhibits morphologic sex differences and is implicated in the control of sexually dimorphic behavior and function. Neurons expressing calcitonin gene-related peptide (CGRP) within the anteroventral periventricular (AVPV) and medial preoptic nucleus (MPN) of the medial preoptic area exhibit female-dominant sex differences in number through organizational and activational effects of gonadal steroids. The present study used retrograde tracing experiments to establish the projections of the AVPV and MPN CGRP neurons in the female rat. After the intraperitoneal administration of Fluoro-Gold to female rats (n = 5), we were unable to detect retrograde tracer in any CGRP-immunoreactive cells of the hypothalamus. Intracerebral injections of 50- to 100-nl volumes of Fluoro-Gold into the mediobasal hypothalamus resulted in up to 70% of CGRP neurons in the AVPV and MPN containing retrograde tracer. Similar large volume tracer depositions in the lateral septum, periaqueductal gray, two likely CGRP projection sites, resulted in no labeling of preoptic CGRP neurons. Experiments using small volume (30-nl) injections of Fluoro-Gold and green fluorescent microspheres at multiple sites in the mediobasal hypothalamus (n = 18) revealed that approximately 60% of AVPV and 30% of MPN neurons expressing CGRP were projecting to the region of the tuberal and ventral premammillary nuclei, with a minor projection to the dorsomedial nucleus. These findings demonstrate a major projection of the preoptic CGRP neurons to the posterior hypothalamus in the female rat and support further a functional role for these neurons in the sexually dimorphic regulation of reproductive functioning.     

Aromatase immunoreactivity in the bluehead wrasse brain, Thalassoma bifasciatum: immunolocalization and co-regionalization with arginine vasotocin and tyrosine hydroxylase

Sex steroid hormones regulate various neural functions that control vertebrate sociosexual behavior. A number of sex steroids can be synthesized de novo in the brain, including estrogens by the enzyme aromatase. Aromatase, the neuropeptides arginine vasotocin/vasopressin, and the monoamine neurotransmitter dopamine have all been implicated in the control of male sexual and aggressive behavior in a variety of vertebrates. This study examined the expression of brain aromatase in the bluehead wrasse (Thalassoma bifasciatum), a teleost fish that exhibits socially controlled behavioral and gonadal sex change. We used immunocytochemistry (ICC) to characterize distributions of aromatase-immunoreactive (ir) cells, and to examine their relationship with AVT-ir neurons and tyrosine hydroxylase-ir (TH-ir) neurons in key sensory and integrative areas of the brain of this species. Aromatase-ir appeared to be in glial cell populations, and was found in the dorsal and ventral telencephalon, the preoptic area of the hypothalamus, and the lateral recess of the third ventricle, among other brain areas. Aromatase-ir fibers are closely associated with AVT-ir neurons throughout the preoptic area, indicating the potential for functional interactions. Aromatase-ir cell bodies and fibers were also co-regionalized with TH-ir neurons, suggesting possible interaction between the dopaminergic system and neural estrogen production. The presence of aromatase in brain regions important in the regulation of sexual and aggressive behavior suggests that local estrogen synthesis could regulate sex change through effects on signaling systems that subserve reproductive behavior and function.     

Sexually dimorphic opioid distribution in the preoptic area: manipulation by gonadal steroids

A striking sexual dimorphism has been found in the density of Met-enkephalin immunoreactive fibers in the periventricular region of the preoptic area in the rat: the enkephalinergic fiber system is much denser in females. The expression of this female-typical fiber plexus is regulated by the actions of gonadal steroids both during development and in adulthood. In light of abundant evidence demonstrating the ability of the opioid peptides to modulate various sexually differentiated neuroendocrine processes and behaviors, this dimorphic system may represent an important anatomical substrate underlying these functions.     

An HRP study of the connections of the subfornical organ of the rat

The connections of the subfornical organ (SFO) wer investigated by using the HRP technique. Injections into the SFO labeled neurons in the medial septum, but not in lateral septum nor in the diagonal band nucleus. Labeled cells were observed in the median preoptic nucleus, below the ependyma of the third ventricle, in the dorsal preoptic region near the anterior commissure, and diffusely throughout the medial preoptic and anterior bypothalamic areas. Fibers were followed from the ventral stalk of the SFO. Precommissural fibers enter the median preoptic nucleus where many of them appear to terminate. Others continue on to the medial septum, the OVLT, the supraoptic nucleus, and the suprachiasmatic nucleus, HRP injections into the median preoptic nucleus labled many neurons in the SFO. Postcommissural fibers reach the hypothalamus by descending along the walls of the ventricle in the subependymal space, by traveling in the columns of the fornix and the medial corticohypothalamic tract, or by passing through the paraventricular nucleus of the thalamus. Some postcommissural fibers turn rostrally and enter the median preoptic nucleus while others join precommissural fibers bound for the supraoptic nucleus. More caudally directed fibers appear to innervate the paraventricular nucleus of the hypothalamus and the medial preoptic and anterior hypothalamic areas. HRP injections into the paraventricular nucleus of the hypothalamus labeled neurons in the SFO. These finding corroborate and extend previous work in describing neural connections between two brain regions that are important for fluid blance.     

Hypothalamic arginine vasotocin mRNA abundance variation across sexes and with sex change in a coral reef fish

Gonadal hormones are important mediators of sexual and aggressive behavior in vertebrates. Recent evidence suggests that the peptide hormones arginine vasotocin (AVT) and its mammalian homologue arginine vasopressin (AVP) often critically mediate these gonadal hormone effects on behavior and have direct influences on behavioral variation. Behavioral differences between sexes, across reproductive states, and even among closely related species are correlated with differences in central AVT/AVP systems in many species. We report differences in hypothalamic AVT mRNA levels between distinct alternate male phenotypes and with female-to-male sex change in the bluehead wrasse (Thalassoma bifasciatum), a teleost fish. The aggressively dominant and strongly courting male phenotype has greater numbers of AVT mRNA producing cells in the magnocellular preoptic area of the hypothalamus than females. Levels of AVT mRNA within these cells in dominant males are also approximately three times female levels whereas the non-aggressive male phenotype has AVT mRNA levels approximately twice female levels. Behavioral sex change is very rapid in this species and is not dependent on the presence of gonads. Conversely, rapid increases in sexual and aggressive behavior during sex change are closely paralleled by approximate fourfold increases in hypothalamic AVT-mRNA levels. The behavioral plasticity shown by bluehead wrasses in response to social environment might be mediated in part by a neuropeptide, AVT, with changes in the gonads and gonadal hormones as the result rather than the cause of behavioral dominance. Copyright (R) 2000 S. Karger AG, Basel     

Sex Differences in the Expression of Sex Steroid Receptor mRNA in the Quail Brain

In Japanese quail, males will readily exhibit the full sequence of male‐typical sexual behaviors but females never show this response, even after ovariectomy and treatment with male‐typical concentrations of exogenous testosterone. Testosterone aromatisation plays a key‐limiting role in the activation of this behavior but the higher aromatase activity in the brain of males compared to females is not sufficient to explain the behavioural sex difference. The cellular and molecular bases of this prominent sex difference in the functional consequences of testosterone have not been identified so far. We hypothesised that the differential expression of sex steroid receptors in specific brain areas could mediate this behavioural sex difference. Therefore, using radioactive in situ hybridisation histochemistry, we quantified the expression of the mRNA coding for the androgen receptor (AR) and the oestrogen receptors (ER) of the α and β subtypes. All three receptors were expressed in an anatomically discrete manner in various nuclei of the hypothalamus and limbic system and, at usually lower densities, in a few other brain areas. In both sexes, the intensity of the hybridisation signal for all steroid receptors was highest in the medial preoptic nucleus (POM), a major site of testosterone action that is related to the activation of male sexual behaviour. Although no sex difference in the optical density of the AR hybridisation signal could be found in POM, the area covered by AR mRNA was significantly larger in males than in females, indicating a higher overall degree of AR expression in this region in males. By contrast, females tended to have significantly higher levels of AR expression than males in the lateral septum. ERα was more densely expressed in females than males throughout the medial preoptic and hypothalamic areas (including the POM and the medio‐basal hypothalamus), an area implicated in the control of female receptivity) and in the mesencephalic nucleus intercollicularis. ERβ was more densely expressed in the medio‐basal hypothalamus of females but a difference in the reverse direction (males > females) was observed in the nucleus taeniae of the amygdala. These data suggest that a differential expression of steroid receptors in specific brain areas could mediate at least certain aspects of the sex differences in behavioural responses to testosterone, although they do not appear to be sufficient to explain the complete lack of activation by testosterone of male‐typical copulatory behaviour in females.     

Sexual dimorphism in the vasotocin system of the bullfrog (Rana catesbeiana).

Arginine vasotocin (AVT) is widespread in amphibian brains, where its levels have been correlated with reproductive behaviors. To better understand which neural systems are involved in central actions of AVT, we used immunocytochemistry to compare the distribution of AVT in the brains of male and female bullfrogs (Rana catesbeiana). AVT-immunoreactive cells were observed in the septal nucleus, amygdala pars lateralis, magnocellular preoptic area, suprachiasmatic nucleus, and hypothalamus. AVT-immunoreactive cells were also found in the pretrigeminal nucleus, but only in animals killed in the fall. Immunoreactive fibers were broadly distributed in hypothalamic and extrahypothalamic areas. The most obvious sex differences were found in the amygdala pars lateralis, where the density of immunoreactive cells and fibers was significantly greater in male than in female bullfrogs. In addition, in the habenular nucleus, males had a denser distribution of AVT-immunoreactive fibers than females. In the suprachiasmatic nucleus, AVT-immunoreactive cells were larger in females than in males but did not differ in number. Since the areas that showed sex differences in AVT distribution have also been implicated in control of reproductive behaviors, they may form the neural substrates for the effects of AVT on sexually dimorphic behaviors in amphibians.     

Vasopressin innervation of sexually dimorphic structures of the gerbil forebrain under various hormonal conditions.

The distribution of vasopressin-immunoreactive fibers in the forebrain of male and female gerbils was studied, focusing on the lateral septum and the sexually dimorphic area (SDA) found at the border between the medial preoptic area and the anterior hypothalamus. To study hormonal influences on the densities of these fibers, some animals of each sex were gonadectomized or gonadectomized and given testosterone. Others were given sham operations. High densities of vasopressin-immunoreactive fibers were found in the lateral septum. In the SDA, the densities of these fibers varied considerably. Many were found in the medial half of the medial SDA, but few in the lateral SDA. Vasopressin-immunoreactive fibers were also sparse in the lateral half of the medial SDA, except for a dense cluster in the SDA pars compacta of males. Similar but smaller clusters were seen in the same location in females although the SDA pars compacta could not be detected in Nissl-stained sections from the female brains. Fiber densities in two areas, the lateral septum and the lateral SDA, were sensitive to gonadal steroids. In both cases, castration reduced fiber density and testosterone enhanced it. In addition, fiber densities in two areas, the lateral septum and the medial SDA, were sexually dimorphic. In each case, fiber density was greater in males. There was no hormonal effect, however, on the fiber densities in the medial SDA. The fact that the fiber plexuses in the lateral septum and the medial SDA respond differently to gonadal steroids suggests that they arise from different cells and possibly from different areas of the brain. The vasopressin-immunoreactive fibers in the lateral septum probably come from steroid-sensitive vasopressin neurons in the bed nucleus of the stria terminalis. Those in the medial SDA may originate in the dorsal aspect of the suprachiasmatic nucleus where vasopressin-immunoreactive cell bodies were seen.     

Sexually dimorphic regions in the medial preoptic area and the bed nucleus of the stria terminalis of the guinea pig brain: a description and an investigation of their relationship to gonadal steroids in adulthood

Sexually dimorphic regions are described in two areas of the guinea pig brain: the medial preoptic area (MPOA) and the bed nucleus of the stria terminalis (BNST). The volume of a darkly staining portion of the MPOA is approximately 4-fold larger in male than in female guinea pigs, and the volume of a darkly staining portion of the BNST is approximately 36% larger in male than in female animals. The sex differences in both of these areas are present in animals that have been gonadectomized as adults as well as in intact animals, suggesting that they result from differences between the sexes in the hormonal environment during early development. Both the MPOA and the BNST bind high levels of gonadal steroids early in life, during the period when functional differentiation occurs. It is possible that dramatic morphological sex differences characterize such steroid-binding areas. Furthermore, these sexually dimorphic areas may form an anatomically and functionally interrelated system. Attention to these possibilities may help elucidate more precisely the neural basis for sexually dimorphic functions, as well as the basic mechanisms underlying sexual differentiation of behavior and the brain.     

Sex-dependent effects of gonadal and gonadotropic hormones on centrally-elicited attack in cats

Sex hormones are selectively taken up by the brain and affect neural activity in regions which are also involved in the mediation and modulation of aggressive behavior. The present investigation was undertaken to study the effects of both the gonadal hormones (estrogen and testosterone) and pituitary gonadotropins (luteinizing and follicle-stimulating hormones) on attack elicited by electrical stimulation of the preoptic area and hypothalamus in both male and female cats. Assessment of the effects of hormone injections and gonadectomy was in terms of changes in latency to attack an anesthetized rat. The results indicated that (1) gonadotropins as well as gonadal steroids affect the response, probably by altering thresholds for its elicitation, and that (2) the direction of these hormone effects is sex-dependent. The latter finding was interpreted in terms of the sexual differentiation of the brain as a result of pre- or neonatal hormone levels.     

Organized for sex - steroid hormones and the developing hypothalamus

Steroid hormones of gonadal origin act on the neonatal brain, particularly the hypothalamus, to produce sex differences that underlie copulatory behavior. Neuroanatomical sex differences include regional volume, cell number, connectivity, morphology, physiology, neurotransmitter phenotype and molecular signaling, all of which are determined by the action of steroid hormones, particularly by estradiol in males, and are established by diverse downstream effects. Sex differences in distinct hypothalamic regions can be organized by the same steroid hormone, but the direction of a sex difference is often specific to one region or cell type, illustrating the wide range of effects that steroid hormones have on the developing brain. Substantial progress has been made in elucidating the downstream mechanisms through which gonadal hormones sexually differentiate the brain, but gaps remain in establishing the precise relationship between changes in neuronal morphology and behavior. A complete understanding of sexual differentiation will require integrating the diverse mechanisms across multiple brain regions into a functional network that regulates behavioral output.     

Sex Differences in Cytosolic Androgen Receptors in Gonadectomized Male and Female Rats

The purpose of this experiment was to determine if there are sex differences in cytosolic androgen receptors (AR) in individual brain nuclei. Bilateral 500  μ diameter samples from 300  μ thick frozen brain sections were micropunched from males and females 2–3 weeks following gonadectomy. Tissue samples were taken from 12 brain nuclei: lateral septum, bed nucleus of the stria terminalis, medial preoptic nucleus, anterior hypothalamic area, arcuate nucleus, corticomedial nucleus of the amygdala, lateral preoptic area, parietal cortex, medial nucleus of the amygdala, dorsomedial nucleus of the hypothalamus, ventromedial nucleus of the hypothalamus, and dorsal hippocampus. Cytosolic ARs were higher in males than in females in each of these 12 areas, but this sex difference was significant only in the first 6. Sex differences in ARs were found in brain regions involved in the neuromodulation of androgen dependent responses. These data suggest that behavioral differences in male reproductive responses may be the result of a sexually dimorphic distribution of androgen receptor containing neurons.     

The relationship between reproductive state and "sexually" dimorphic brain areas in sexually reproducing and parthenogenetic whiptail lizards

The anterior hypothalamus-preoptic area and ventromedial hypothalamus are sexually dimorphic in the reproductively active whiptail lizard Cnemidophorus inornatus. The anterior hypothalamus-preoptic area, which is involved in the control of male-typical copulatory behaviors, is larger in males, whereas the ventromedial hypothalamus, which is involved in the control of female-typical receptivity, is larger in females. In the parthenogenetic whiptail lizard C. uniparens, which is a direct descendant of C. inornatus and exhibits both male-like and female-like pseudosexual behaviors, both brain areas are comparable in size to those of female C. inornatus. This study was conducted to determine whether these brain areas change in size in either species or sex during a time of year when these animals are reproductively inactive, or after removal of the gonads. In male C. inornatus both brain areas changed during reproductive inactivity (either seasonally or surgically induced) and became equivalent to the size characteristic of reproductively active female C. inornatus. When corrected for brain size, the anterior hypothalamus-preoptic area was significantly smaller in intact hibernating and castrated males than in intact males from the summer breeding season. Conversely, the ventromedial hypothalamus was significantly larger in intact hibernating and castrated males than in intact males from the summer breeding season. The two brain areas were not significantly different among the groups of female C. inornatus or parthenogenetic C. uniparens. These results suggest that 1) the brain of whiptail lizards may differentiate seasonally and 2) the female state may be a neutral one to which the male brain reverts during reproductive inactivity.     

Developmental sculpting of social phenotype and plasticity

Early developmental variables engender behavioral and neural variation, especially in species in which embryonic environment determines gonadal sex. In the leopard gecko, Eublepharis macularius, the incubation temperature of the egg (IncT) determines gonadal sex. Moreover, IncT affects the sexual differentiation of the individual and, consequently, within-sex variation. Individuals hatched from eggs incubated at an IncT that produces predominantly males are more masculinized than same-sex counterparts from IncTs that produce predominantly females. Here we review how gonadal sex and IncT interact to affect behavioral, endocrinological, and neural phenotype in the leopard gecko and influence phenotypic plasticity following hormone administration or social experience. We discuss the hormonal dependence of sex- and IncT-dependent behavioral and neural morphological and metabolic differences and highlight the parallels between IncT effects in geckos and intrauterine position effects in rodents. We argue that the leopard gecko is an important model of how the process of sex determination can affect sexual differentiation and of selection forces underlying the evolution of sex ratios.     

Efferents from medial basal forebrain and hypothalamus in the rat. II. An autoradiographic study of the anterior hypothalamus.

Using tritiated amino acid autoradiography, the efferent projections of the anterior hypothalamic area (AHA) were studied in albino rats. Axons from AHA neurons were not confined to local projections in the hypothalamus. Ascending AHA axons ran through the preoptic region, joined the diagonal band and distributed in the lateral septum. Descending AHA efferents within the hypothalamus coursed in a bundle ventromedial to the fornix. Projections were observed to the dorsomedial, ventromedial, arcuate and dorsal premammillary nuclei, and to the median eminence. Sweeping dorsomedially in the posterior hypothalamus, some AHA axons distributed in the central grey. AHA axons staying ventral projected to the supramammillary region, ventral tegmental area, raphe nuclei and midbrain reticular formation. Other AHA efferents distributed to the periventricular thalamus, to the medial amygdala via the stria terminalis or supraoptic commissure, and to the lateral habenula through the stria medullaris. For comparison with the AHA, efferent projections from the paraventricular nucleus (PVN) and from the ventromedial nucleus and adjacent basal hypothalamus (VMR) were studied. Projections from PVN neurons were not restricted to the median eminence and neurohypophysis. PVN efferents also distributed to many of the same regions as did those of the AHA but had somewhat different fiber trajectories and longer descending projections. VMR efferents were more widespread than those of the AHA, with projections extending into the lateral zona incerta and pontine reticular formation. Projections from the AHA were distinct from those of the medial preoptic area (mPOA). For example, while AHA axons descended in a bundle ventromedial to the fornix, mPOA axons ran in the medial forebrain bundle. Such anatomical differences may underlie experimentally demonstrated functional differences between the mPOA and AHA, for instance, in mediation of male and female sex behaviors.     

Cell death atlas of the postnatal mouse ventral forebrain and hypothalamus: Effects of age and sex

Naturally occurring cell death is essential to the development of the mammalian nervous system. Although the importance of developmental cell death has been appreciated for decades, there is no comprehensive account of cell death across brain areas in the mouse. Moreover, several regional sex differences in cell death have been described for the ventral forebrain and hypothalamus, but it is not known how widespread the phenomenon is. We used immunohistochemical detection of activated caspase‐3 to identify dying cells in the brains of male and female mice from postnatal day (P) 1 to P11. Cell death density, total number of dying cells, and regional volume were determined in 16 regions of the hypothalamus and ventral forebrain (the anterior hypothalamus, arcuate nucleus, anteroventral periventricular nucleus, medial preoptic nucleus, paraventricular nucleus, suprachiasmatic nucleus, and ventromedial nucleus of the hypothalamus; the basolateral, central, and medial amygdala; the lateral and principal nuclei of the bed nuclei of the stria terminalis; the caudate‐putamen; the globus pallidus; the lateral septum; and the islands of Calleja). All regions showed a significant effect of age on cell death. The timing of peak cell death varied between P1 to P7, and the average rate of cell death varied tenfold among regions. Several significant sex differences in cell death and/or regional volume were detected. These data address large gaps in the developmental literature and suggest interesting region‐specific differences in the prevalence and timing of cell death in the hypothalamus and ventral forebrain. J. Comp. Neurol. 521:2551–2569, 2013. © 2013 Wiley Periodicals, Inc.