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Acta Neurobiologiae Experimentalis 1981Horseradish peroxidase (HRP) was injected into various nuclei of the amygdala in 50 rats. The retrograde axonal transport of HRP showed various connections arising from...
Horseradish peroxidase (HRP) was injected into various nuclei of the amygdala in 50 rats. The retrograde axonal transport of HRP showed various connections arising from the hypothalamic nuclei and the basal forebrain. Neurons of the magnocellular preoptic nucleus send out amygdalopetal axons to all amygdaloid nuclei except the lateral nucleus. The amygdalopetal projections emerge from the large neurons situated dorsally in the most lateral preoptic area (probably substantia innominata) and terminate in the basal dorsal and the central amygdaloid nuclei. Neurons in the lateral division of the hypothalamus (the lateral hypothalamic area proper and the perifarnical region) send out axons which terminate in the medial and central nuclei and in the posterior part of the cortical amygdaloid nucleus. Axons emerging from the ventromedial hypothalamic nucleus end mainly in the medial nucleus and in the central amygdaloid nucleus. Amygdalopetal fibers arising from neurons of the ventral premammillary and dorsal hypothalamic nuclei reach the medial amygdaloid nucleus and perhaps a few of them end in the posterior part of the cortical amygdaloid nucleus. Neurons of the bed nucleus of the stria terminalis project to the medial, the posterior part of the cortical and probably to the basal dorsal amygdaloid nuclei.
Topics: Amygdala; Animals; Axons; Female; Horseradish Peroxidase; Hypothalamus; Male; Neurons; Preoptic Area; Rats; Synaptic Transmission
PubMed: 6267903
DOI: No ID Found -
PloS One 2015Testosterone plays an essential role in sexual differentiation of the male sheep brain. The ovine sexually dimorphic nucleus (oSDN), is 2 to 3 times larger in males than...
Testosterone plays an essential role in sexual differentiation of the male sheep brain. The ovine sexually dimorphic nucleus (oSDN), is 2 to 3 times larger in males than in females, and this sex difference is under the control of testosterone. The effect of testosterone on oSDN volume may result from enhanced expansion of soma areas and/or dendritic fields. To test this hypothesis, cells derived from the hypothalamus-preoptic area (HPOA) and cerebral cortex (CTX) of lamb fetuses were grown in primary culture to examine the direct morphological effects of testosterone on these cellular components. We found that within two days of plating, neurons derived from both the HPOA and CTX extend neuritic processes and express androgen receptors and aromatase immunoreactivity. Both treated and control neurites continue to grow and branch with increasing time in culture. Treatment with testosterone (10 nM) for 3 days significantly (P < 0.05) increased both total neurite outgrowth (35%) and soma size (8%) in the HPOA and outgrowth (21%) and number of branch points (33%) in the CTX. These findings indicate that testosterone-induced somal enlargement and neurite outgrowth in fetal lamb neurons may contribute to the development of a fully masculine sheep brain.
Topics: Animals; Cell Proliferation; Cell Shape; Cells, Cultured; Cerebral Cortex; Female; Fetus; Immunohistochemistry; Male; Neurites; Preoptic Area; Sheep; Testosterone; Time Factors
PubMed: 26053052
DOI: 10.1371/journal.pone.0129521 -
Frontiers in Neuroendocrinology Oct 2007Several studies have suggested dissociations between neural circuits underlying the expression of appetitive (e.g., courtship behavior) and consummatory components... (Review)
Review
Several studies have suggested dissociations between neural circuits underlying the expression of appetitive (e.g., courtship behavior) and consummatory components (i.e., copulatory behavior) of vertebrate male sexual behavior. The medial preoptic area (mPOA) clearly controls the expression of male copulation but, according to a number of experiments, is not necessarily implicated in the expression of appetitive sexual behavior. In rats for example, lesions to the mPOA eliminate male-typical copulatory behavior but have more subtle or no obvious effects on measures of sexual motivation. Rats with such lesions still pursue and attempt to mount females. They also acquire and perform learned instrumental responses to gain access to females. However, recent lesions studies and measures of the expression of the immediate early gene c-fos demonstrate that, in quail, sub-regions of the mPOA, in particular of its sexually dimorphic component the medial preoptic nucleus, can be specifically linked with either the expression of appetitive or consummatory sexual behavior. In particular more rostral regions can be linked to appetitive components while more caudal regions are involved in consummatory behavior. This functional sub-region variation is associated with neurochemical and hodological specializations (i.e., differences in chemical phenotype of the cells or in their connectivity), especially those related to the actions of androgens in relation to the activation of male sexual behavior, that are also present in rodents and other species. It could thus reflect general principles about POA organization and function in the vertebrate brain.
Topics: Animals; Appetite; Consummatory Behavior; Genes, fos; Humans; Male; Mice; Motivation; Nerve Net; Preoptic Area; Quail; Rats; Sexual Behavior; Sexual Behavior, Animal; Testosterone
PubMed: 17624413
DOI: 10.1016/j.yfrne.2007.05.003 -
The Journal of Neuroscience : the... May 2016The preoptic area (POA) regulates body temperature, but is not considered a site for body weight control. A subpopulation of POA neurons express leptin receptors...
UNLABELLED
The preoptic area (POA) regulates body temperature, but is not considered a site for body weight control. A subpopulation of POA neurons express leptin receptors (LepRb(POA) neurons) and modulate reproductive function. However, LepRb(POA) neurons project to sympathetic premotor neurons that control brown adipose tissue (BAT) thermogenesis, suggesting an additional role in energy homeostasis and body weight regulation. We determined the role of LepRb(POA) neurons in energy homeostasis using cre-dependent viral vectors to selectively activate these neurons and analyzed functional outcomes in mice. We show that LepRb(POA) neurons mediate homeostatic adaptations to ambient temperature changes, and their pharmacogenetic activation drives robust suppression of energy expenditure and food intake, which lowers body temperature and body weight. Surprisingly, our data show that hypothermia-inducing LepRb(POA) neurons are glutamatergic, while GABAergic POA neurons, originally thought to mediate warm-induced inhibition of sympathetic premotor neurons, have no effect on energy expenditure. Our data suggest a new view into the neurochemical and functional properties of BAT-related POA circuits and highlight their additional role in modulating food intake and body weight.
SIGNIFICANCE STATEMENT
Brown adipose tissue (BAT)-induced thermogenesis is a promising therapeutic target to treat obesity and metabolic diseases. The preoptic area (POA) controls body temperature by modulating BAT activity, but its role in body weight homeostasis has not been addressed. LepRb(POA) neurons are BAT-related neurons and we show that they are sufficient to inhibit energy expenditure. We further show that LepRb(POA) neurons modulate food intake and body weight, which is mediated by temperature-dependent homeostatic responses. We further found that LepRb(POA) neurons are stimulatory glutamatergic neurons, contrary to prevalent models, providing a new view on thermoregulatory neural circuits. In summary, our study significantly expands our current understanding of central circuits and mechanisms that modulate energy homeostasis.
Topics: Adipose Tissue, Brown; Animals; Body Temperature; Body Temperature Regulation; Body Weight; Eating; Energy Metabolism; Glutamates; Homeostasis; Mice; Neurons; Preoptic Area; Receptors, Adrenergic, beta-3; Receptors, Leptin; Temperature
PubMed: 27147656
DOI: 10.1523/JNEUROSCI.0213-16.2016 -
Nature May 2021Innate vocal sounds such as laughing, screaming or crying convey one's feelings to others. In many species, including humans, scaling the amplitude and duration of...
Innate vocal sounds such as laughing, screaming or crying convey one's feelings to others. In many species, including humans, scaling the amplitude and duration of vocalizations is essential for effective social communication. In mice, female scent triggers male mice to emit innate courtship ultrasonic vocalizations (USVs). However, whether mice flexibly scale their vocalizations and how neural circuits are structured to generate flexibility remain largely unknown. Here we identify mouse neurons from the lateral preoptic area (LPOA) that express oestrogen receptor 1 (LPOA neurons) and, when activated, elicit the complete repertoire of USV syllables emitted during natural courtship. Neural anatomy and functional data reveal a two-step, di-synaptic circuit motif in which primary long-range inhibitory LPOA neurons relieve a clamp of local periaqueductal grey (PAG) inhibition, enabling excitatory PAG USV-gating neurons to trigger vocalizations. We find that social context shapes a wide range of USV amplitudes and bout durations. This variability is absent when PAG neurons are stimulated directly; PAG-evoked vocalizations are time-locked to neural activity and stereotypically loud. By contrast, increasing the activity of LPOA neurons scales the amplitude of vocalizations, and delaying the recovery of the inhibition clamp prolongs USV bouts. Thus, the LPOA disinhibition motif contributes to flexible loudness and the duration and persistence of bouts, which are key aspects of effective vocal social communication.
Topics: Animals; Courtship; Estrogen Receptor alpha; Female; Hypothalamus; Male; Mice; Mice, Inbred BALB C; Neurons; Periaqueductal Gray; Preoptic Area; Synapses; Time Factors; Ultrasonic Waves; Vocalization, Animal
PubMed: 33790464
DOI: 10.1038/s41586-021-03403-8 -
Neuroendocrinology 2017The aim of this immunohistochemical study was to evaluate the distribution of kisspeptin neurons in the preoptic area (POA) of gonadally intact adult male and female...
Estradiol Upregulates Kisspeptin Expression in the Preoptic Area of both the Male and Female Rhesus Monkey (Macaca mulatta): Implications for the Hypothalamic Control of Ovulation in Highly Evolved Primates.
The aim of this immunohistochemical study was to evaluate the distribution of kisspeptin neurons in the preoptic area (POA) of gonadally intact adult male and female rhesus monkeys, and to determine whether imposition of an estradiol (E2)-positive feedback signal in the castrate male increased kisspeptin in the POA. Additionally, kisspeptin in the POA of the intact female was examined during an LH surge induced prematurely by E2 administered in the early follicular phase. The number of kisspeptin neurons in the POA of males and females was similar. Immunoactive kisspeptin perikarya were not observed in the POA of castrate adult males, but such neurons in these animals were present within 12 h of imposing an increment in circulating E2 concentrations that in a screening study conducted 4-6 weeks earlier had elicited an LH surge. As expected, premature induction of an LH surge by E2 early in the follicular phase was associated with upregulation of kisspeptin in the POA. These results represent the first description of immunoreactive kisspeptin cell bodies in the POA of the macaque brain and provide further support for the view that (1) kisspeptin neurons in the POA of the female monkey are a target for the positive feedback action of E2 and (2) the hypothalamic mechanism which mediates this action of E2 in primates is not subjected to perinatal programming by testicular testosterone. Moreover, our findings indicate that maintenance of the kisspeptin content in the POA of intact male monkeys requires the action of E2, presumably generated by aromatization of testicular testosterone at the hypothalamic level.
Topics: Analysis of Variance; Animals; Antibodies; Castration; Cell Count; Estradiol; Estrogens; Female; Follicular Phase; Humans; Hysterectomy; Kisspeptins; Luteinizing Hormone; Macaca mulatta; Male; Neurons; Ovulation; Preoptic Area; Sex Characteristics; Up-Regulation; Vasopressins
PubMed: 27454155
DOI: 10.1159/000448520 -
Endocrinology Nov 2020Polycystic ovary syndrome (PCOS) is the most common form of infertility in women. The causes of PCOS are not yet understood and both genetics and early-life exposure...
Polycystic ovary syndrome (PCOS) is the most common form of infertility in women. The causes of PCOS are not yet understood and both genetics and early-life exposure have been considered as candidates. With regard to the latter, circulating androgens are elevated in mid-late gestation in women with PCOS, potentially exposing offspring to elevated androgens in utero; daughters of women with PCOS are at increased risk for developing this disorder. Consistent with these clinical observations, prenatal androgenization (PNA) of several species recapitulates many phenotypes observed in PCOS. There is increasing evidence that symptoms associated with PCOS, including elevated luteinizing hormone (LH) (and presumably gonadotropin-releasing hormone [GnRH]) pulse frequency emerge during the pubertal transition. We utilized translating ribosome affinity purification coupled with ribonucleic acid (RNA) sequencing to examine GnRH neuron messenger RNAs from prepubertal (3 weeks) and adult female control and PNA mice. Prominent in GnRH neurons were transcripts associated with protein synthesis and cellular energetics, in particular oxidative phosphorylation. The GnRH neuron transcript profile was affected more by the transition from prepuberty to adulthood than by PNA treatment; however, PNA did change the developmental trajectory of GnRH neurons. This included families of transcripts related to both protein synthesis and oxidative phosphorylation, which were more prevalent in adults than in prepubertal mice but were blunted in PNA adults. These findings suggest that prenatal androgen exposure can program alterations in the translatome of GnRH neurons, providing a mechanism independent of changes in the genetic code for altered expression.
Topics: Androgens; Animals; Female; Gene Expression Regulation, Developmental; Gonadotropin-Releasing Hormone; Male; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Transgenic; Neurogenesis; Neurons; Pregnancy; Prenatal Exposure Delayed Effects; Preoptic Area; RNA, Messenger; Sex Factors; Virilism
PubMed: 33095238
DOI: 10.1210/endocr/bqaa166 -
The Journal of Neuroscience : the... Mar 2020Fever is a common phenomenon during infection or inflammatory conditions. This stereotypic rise in body temperature (Tb) in response to inflammatory stimuli is a result...
Fever is a common phenomenon during infection or inflammatory conditions. This stereotypic rise in body temperature (Tb) in response to inflammatory stimuli is a result of autonomic responses triggered by prostaglandin E2 action on EP3 receptors expressed by neurons in the median preoptic nucleus (MnPO neurons). To investigate the identity of MnPO neurons, we first used hybridization to show coexpression of EP3R and the VGluT2 transporter in MnPO neurons. Retrograde tracing showed extensive direct projections from MnPO but few from MnPO neurons to a key site for fever production, the raphe pallidus. Ablation of MnPO but not MnPO neurons abolished fever responses but not changes in Tb induced by behavioral stress or thermal challenges. Finally, we crossed EP3R conditional knock-out mice with either VGluT2-IRES-cre or Vgat-IRES-cre mice and used both male and female mice to confirm that the neurons that express EP3R and mediate fever are glutamatergic, not GABAergic. This finding will require rethinking current concepts concerning the central thermoregulatory pathways based on the MnPO neurons being GABAergic. Body temperature is regulated by the CNS. The rise of the body temperature, or fever, is an important brain-orchestrated mechanism for fighting against infectious or inflammatory disease, and is tightly regulated by the neurons located in the median preoptic nucleus (MnPO). Here we demonstrate that excitatory MnPO neurons mediate fever and examine a potential central circuit underlying the development of fever responses.
Topics: Animals; Body Temperature; Body Temperature Regulation; Female; Fever; Globus Pallidus; Glutamic Acid; Inflammation; Lipopolysaccharides; Male; Mice; Mice, Knockout; Motor Activity; Neural Pathways; Neurons; Preoptic Area; Receptors, Prostaglandin E, EP3 Subtype; Stress, Psychological; Vesicular Glutamate Transport Protein 2
PubMed: 32079648
DOI: 10.1523/JNEUROSCI.2887-19.2020 -
BMC Neuroscience Jan 2014The mother-child relationship is the most fundamental social bond in mammals, and previous studies indicate that the medial preoptic area (MPOA) contributes to this...
BACKGROUND
The mother-child relationship is the most fundamental social bond in mammals, and previous studies indicate that the medial preoptic area (MPOA) contributes to this increase in sociability. It is possible that the same genes that lead to elevated sociability in one condition (the maternal state) might also be dysregulated in some disorders with social deficits (e.g. autism). In this study, we examined whether there was enrichment (greater than chance overlap) for social deficit disorder related genes in MPOA microarray results between virgin and postpartum female mice. We utilized microarrays to assess large scale gene expression changes in the MPOA of virgin and postpartum mice. The Modular Single Set Enrichment Test (MSET) was used to determine if mental health disorder related genes were enriched in significant microarray results. Additional resources, such as ToppCluster, NIH DAVID, and weighted co-expression network analysis (WGCNA) were used to analyze enrichment for specific gene clusters or indirect relationships between significant genes of interest. Finally, a subset of microarray results was validated using quantitative PCR.
RESULTS
Significant postpartum MPOA microarray results were enriched for multiple disorders that include social deficits, including autism, bipolar disorder, depression, and schizophrenia. Together, 98 autism-related genes were identified from the significant microarray results. Further, ToppCluser and NIH DAVID identified a large number of postpartum genes related to ion channel activity and CNS development, and also suggested a role for microRNAs in regulating maternal gene expression. WGCNA identified a module of genes associated with the postpartum phenotype, and identified indirect links between transcription factors and other genes of interest.
CONCLUSION
The transition to the maternal state involves great CNS plasticity and increased sociability. We identified multiple novel genes that overlap between the postpartum MPOA (high sociability) and mental health disorders with low sociability. Thus, the activity or interactions of the same genes may be altering social behaviors in different directions in different conditions. Maternity also involves elevated risks for disorders, including depression, psychosis, and BPD, so identification of maternal genes common to these disorders may provide insights into the elevated vulnerability of the maternal brain.
Topics: Animals; Animals, Newborn; Biomarkers; Child Development Disorders, Pervasive; Female; Gene Expression Regulation; Humans; Maternal Behavior; Mice; Mice, Inbred ICR; Mother-Child Relations; Mothers; Nerve Tissue Proteins; Phenotype; Preoptic Area; Social Behavior; Social Behavior Disorders
PubMed: 24423034
DOI: 10.1186/1471-2202-15-11 -
Proceedings of the National Academy of... Dec 2021Sleep and wakefulness are not simple, homogenous all-or-none states but represent a spectrum of substates, distinguished by behavior, levels of arousal, and brain...
Sleep and wakefulness are not simple, homogenous all-or-none states but represent a spectrum of substates, distinguished by behavior, levels of arousal, and brain activity at the local and global levels. Until now, the role of the hypothalamic circuitry in sleep-wake control was studied primarily with respect to its contribution to rapid state transitions. In contrast, whether the hypothalamus modulates within-state dynamics (state "quality") and the functional significance thereof remains unexplored. Here, we show that photoactivation of inhibitory neurons in the lateral preoptic area (LPO) of the hypothalamus of adult male and female laboratory mice does not merely trigger awakening from sleep, but the resulting awake state is also characterized by an activated electroencephalogram (EEG) pattern, suggesting increased levels of arousal. This was associated with a faster build-up of sleep pressure, as reflected in higher EEG slow-wave activity (SWA) during subsequent sleep. In contrast, photoinhibition of inhibitory LPO neurons did not result in changes in vigilance states but was associated with persistently increased EEG SWA during spontaneous sleep. These findings suggest a role of the LPO in regulating arousal levels, which we propose as a key variable shaping the daily architecture of sleep-wake states.
Topics: Animals; Dexmedetomidine; Electroencephalography; Female; Glutamate Decarboxylase; Homeostasis; Male; Mice; Optogenetics; Preoptic Area; Sleep
PubMed: 34903646
DOI: 10.1073/pnas.2101580118