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BMC Neuroscience Nov 2023The medial preoptic area (mPOA) regulates the probability and intensity of singing behavior in birds. Polzin and colleagues examined the molecular changes in the mPOA...
The medial preoptic area (mPOA) regulates the probability and intensity of singing behavior in birds. Polzin and colleagues examined the molecular changes in the mPOA that were associated with gregarious song in European starlings (Sturnus vulgaris). High-throughput transcriptome analyses identified glutamate and dopamine pathways were highly enriched with gregarious song.
Topics: Animals; Vocalization, Animal; Sexual Behavior, Animal; Social Behavior; Starlings; Dopamine; Preoptic Area
PubMed: 37919674
DOI: 10.1186/s12868-023-00833-0 -
Frontiers in Neuroscience 2023The medial amygdala (MeA) is a sexually dimorphic brain region that regulates fear responses, emotional memories, and social behaviors. It is known to be larger and...
The medial amygdala (MeA) is a sexually dimorphic brain region that regulates fear responses, emotional memories, and social behaviors. It is known to be larger and contains more cells in males. The MeA integrates information through input connections from olfactory regions, bed nucleus of the stria terminalis, ventral hippocampus, and thalamic and hypothalamic structures. We hypothesize that in addition to the size differences, there are differences in regional connectivity between the sexes. In this study, we utilized G-deleted rabies monosynaptic retrograde tracing to compare amygdala presynaptic cells in male and female whole mouse brains. We report differences in connection patterns to the amygdala, with higher overall connectivity (presynaptic per starter) in males and a larger fraction of inputs originating from the bed nucleus of the stria terminalis, lateral septum, and medial preoptic area. Furthermore, we examined input connections to the orbital cortex (ORB), a brain region shown to be larger in volume in females, and found the opposite trend, where females had more total inputs. Together, our findings extend the evidence for sexual dimorphism in the brain to the neuronal wiring pattern, with likely impacts on behavior and disease susceptibility.
PubMed: 37901417
DOI: 10.3389/fnins.2023.1258284 -
Frontiers in Endocrinology 2023The neuroendocrine control of ovulation is orchestrated by neuronal circuits that ultimately drive the release of gonadotropin-releasing hormone (GnRH) from the...
BACKGROUND
The neuroendocrine control of ovulation is orchestrated by neuronal circuits that ultimately drive the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus to trigger the preovulatory surge in luteinizing hormone (LH) secretion. While estrogen feedback signals are determinant in triggering activation of GnRH neurons, through stimulation of afferent kisspeptin neurons in the rostral periventricular area of the third ventricle (RP3V neurons), many neuropeptidergic and classical neurotransmitter systems have been shown to regulate the LH surge. Among these, several lines of evidence indicate that the monoamine neurotransmitter serotonin (5-HT) has an excitatory, permissive, influence over the generation of the surge, activation of type 2 5-HT (5-HT) receptors. The mechanisms through which this occurs, however, are not well understood. We hypothesized that 5-HT exerts its influence on the surge by stimulating RP3V neurons in a 5-HT receptor-dependent manner.
METHODS
We tested this using kisspeptin neuron-specific calcium imaging and electrophysiology in brain slices obtained from male and female mice.
RESULTS
We show that exogenous 5-HT reversibly increases the activity of the majority of RP3V neurons. This effect is more prominent in females than in males, is likely mediated directly at RP3V neurons and requires activation of 5-HT receptors. The functional impact of 5-HT on RP3V neurons, however, does not significantly vary during the estrous cycle.
CONCLUSION
Taken together, these data suggest that 5-HT receptor-mediated stimulation of RP3V neuron activity might be involved in mediating the influence of 5-HT on the preovulatory LH surge.
Topics: Mice; Female; Male; Animals; Preoptic Area; Kisspeptins; Serotonin; Neurons; Gonadotropin-Releasing Hormone; Receptors, Serotonin; Neurotransmitter Agents
PubMed: 37900129
DOI: 10.3389/fendo.2023.1212854 -
Biomedicines Sep 2023Autism spectrum disorder (ASD) is rather common, presenting with prevalent early problems in social communication and accompanied by repetitive behavior. As vasopressin... (Review)
Review
Autism spectrum disorder (ASD) is rather common, presenting with prevalent early problems in social communication and accompanied by repetitive behavior. As vasopressin was implicated not only in salt-water homeostasis and stress-axis regulation, but also in social behavior, its role in the development of ASD might be suggested. In this review, we summarized a wide range of problems associated with ASD to which vasopressin might contribute, from social skills to communication, motor function problems, autonomous nervous system alterations as well as sleep disturbances, and altered sensory information processing. Beside functional connections between vasopressin and ASD, we draw attention to the anatomical background, highlighting several brain areas, including the paraventricular nucleus of the hypothalamus, medial preoptic area, lateral septum, bed nucleus of stria terminalis, amygdala, hippocampus, olfactory bulb and even the cerebellum, either producing vasopressin or containing vasopressinergic receptors (presumably V). Sex differences in the vasopressinergic system might underline the male prevalence of ASD. Moreover, vasopressin might contribute to the effectiveness of available off-label therapies as well as serve as a possible target for intervention. In this sense, vasopressin, but paradoxically also V receptor antagonist, were found to be effective in some clinical trials. We concluded that although vasopressin might be an effective candidate for ASD treatment, we might assume that only a subgroup (e.g., with stress-axis disturbances), a certain sex (most probably males) and a certain brain area (targeting by means of virus vectors) would benefit from this therapy.
PubMed: 37892977
DOI: 10.3390/biomedicines11102603 -
Heliyon Oct 2023Isoliquiritigenin (ILTG) is a chalcone compound that exhibits hypnotic effects via gamma-aminobutyric acid type A (GABA) receptors. The ventrolateral preoptic area...
OBJECTIVE
Isoliquiritigenin (ILTG) is a chalcone compound that exhibits hypnotic effects via gamma-aminobutyric acid type A (GABA) receptors. The ventrolateral preoptic area (VLPO) is a sleep-promoting center that contains a large number of GABA-releasing cells. There are two cell types in the VLPO: one generates a low-threshold spike (LTS), whereas the other lacks an LTS (non-LTS).
METHOD
Whole-cell patch-clamp technology was used to detect the firing and currents of LTS and non-LTS cells in the VLPO.
RESULTS
Bath administration of ILTG (10 μM) increased the firing rate of VLPO LTS cells, reversed by flumazenil (5 μM), a GABA benzodiazepine site antagonist. However, the firing rate of VLPO non-LTS cells was inhibited by ILTG (10 μM), also reversed by flumazenil (5 μM). No differences were detected regarding resting membrane potential (RMP) amplitude, spike threshold, afterhyperpolarization (AHP) amplitude, or action potential duration (APD) after ILTG (10 μM) perfusion in VLPO LTS cells. RMP amplitude was more hyperpolarized and spike threshold was higher after ILTG (10 μM) application in VLPO non-LTS cells. In addition, ILTG significantly reduced the frequency of miniature inhibitory postsynaptic currents (mIPSCs) in VLPO LTS cells. ILTG significantly increased the amplitude of mIPSCs in VLPO non-LTS cells.
CONCLUSIONS
This study revealed that ILTG suppresses presynaptic GABA release on VLPO LTS cells, thereby increasing their excitability. ILTG enhances postsynaptic GABA receptor function on VLPO non-LTS cells, thereby decreasing their excitability. These results suggest that ILTG may produce hypnotic effects by modulating the GABAergic synaptic transmission properties of these two cell types.
PubMed: 37876454
DOI: 10.1016/j.heliyon.2023.e20620 -
PLoS Genetics Oct 2023Imprinted genes are subject to germline epigenetic modification resulting in parental-specific allelic silencing. Although genomic imprinting is thought to be important...
Imprinted genes are subject to germline epigenetic modification resulting in parental-specific allelic silencing. Although genomic imprinting is thought to be important for maternal behaviour, this idea is based on serendipitous findings from a small number of imprinted genes. Here, we undertook an unbiased systems biology approach, taking advantage of the recent delineation of specific neuronal populations responsible for controlling parental care, to test whether imprinted genes significantly converge to regulate parenting behaviour. Using single-cell RNA sequencing datasets, we identified a specific enrichment of imprinted gene expression in a recognised "parenting hub", the galanin-expressing neurons of the preoptic area. We tested the validity of linking enriched expression in these neurons to function by focusing on MAGE family member L2 (Magel2), an imprinted gene not previously linked to parenting behaviour. We confirmed expression of Magel2 in the preoptic area galanin expressing neurons. We then examined the parenting behaviour of Magel2-null(+/p) mice. Magel2-null mothers, fathers and virgin females demonstrated deficits in pup retrieval, nest building and pup-directed motivation, identifying a central role for this gene in parenting. Finally, we show that Magel2-null mothers and fathers have a significant reduction in POA galanin expressing cells, which in turn contributes to a reduced c-Fos response in the POA upon exposure to pups. Our findings identify a novel imprinted gene that impacts parenting behaviour and, moreover, demonstrates the utility of using single-cell RNA sequencing data to predict gene function from expression and in doing so here, have identified a purposeful role for genomic imprinting in mediating parental behaviour.
Topics: Female; Animals; Mice; Galanin; Parenting; Hypothalamus; Genomic Imprinting; Phenotype; Antigens, Neoplasm; Proteins
PubMed: 37856383
DOI: 10.1371/journal.pgen.1010961 -
Scientific Reports Oct 2023Diabetes mellitus (DM) is a chronic metabolic disease, characterized by persistent hyperglycemia resulting from diminished insulin secretion or insulin resistance. The...
Diabetes mellitus (DM) is a chronic metabolic disease, characterized by persistent hyperglycemia resulting from diminished insulin secretion or insulin resistance. The present study evaluated the ameliorative effects of Withaferin-A (WA) on DM-induced reproductive dysfunction in mice. For the same, mice were intraperitoneally injected with Streptozotocin (STZ), (40 mg/kg/day) for 5 consecutive days to induce DM. Mice were then treated with WA (8 mg/kg/day) in normal and diabetic conditions (STZ + WA). Next, blood glucose levels, oral glucose tolerance, intraperitoneal insulin tolerance, oxidative stress and reproductive parameters were estimated. For reproductive performance, immunofluorescent localization of gonadotropin-releasing hormone (GnRH-I) and estrogen receptor alpha (ERα) in the preoptic area and paraventricular nucleus region of hypothalamus and ERα in testes was performed. STZ-induced diabetes triggered reproductive dysfunctions as mediated by low GnRH-I and ERα in the brain and ERα in the testes along with declined testosterone and estradiol levels. Treatment with WA significantly reduced the blood glucose levels and enhanced glucose clearance accompanied by reduced oxidative stress in the brain, pancreas and testes as indicated by the low levels of HO and MDA in diabetic mice treated with WA (STZ + WA). This study reports, for the first time, that WA can efficiently ameliorate DM-induced reproductive dysfunctions by enhancing endogenous testosterone, estrogen and increased GnRH-I and ERα in the brain and ERα in the testes of DM-induced male mice.
Topics: Animals; Male; Mice; Blood Glucose; Brain; Diabetes Mellitus, Experimental; Estrogen Receptor alpha; Gonadotropin-Releasing Hormone; Hydrogen Peroxide; Streptozocin; Testis; Testosterone; Withanolides
PubMed: 37848702
DOI: 10.1038/s41598-023-44904-y -
Brain Research Bulletin Nov 2023Xenin is a 25-amino acid peptide identified in human gastric mucosa, which is widely expressed in peripheral and central tissues. It is known that the central or...
Xenin is a 25-amino acid peptide identified in human gastric mucosa, which is widely expressed in peripheral and central tissues. It is known that the central or peripheral administration of xenin decreases food intake in rodents. Nesfatin-1/NUCB2 (nesfatin-1) has been identified as an anorexic neuropeptide, it is often found co-localized with many peptides in the central nervous system. After the intracerebroventricular administration of xenin on nesfain-1-like immunoreactivity (LI) neurons, we examined its effects on food intake and water intake in rats. As a result, Fos-LI neurons were observed in the organum vasculosum of the laminae terminalis (OVLT), the median preoptic nucleus (MnPO), the subfornical organ (SFO), the supraoptic nucleus (SON), the paraventricular nucleus (PVN), the arcuate nucleus (Arc), the lateral hypothalamic area (LHA), the central amygdaloid nucleus (CAN), the dorsal raphe nucleus (DR), the locus coeruleus (LC), the area postrema (AP) and the nucleus of the solitary tract (NTS). After the administration, the number of Fos-LI neurons was significantly increased in the LC and the OVLT, the MnPO, the SFO, the SON, the PVN, the Arc, the LHA, the CAN, the DR, the AP and the NTS, compared with the control group. After the administration of xenin, we conducted double immunohistochemistry for Fos and nesfatin-1, and found that the number of nesfatin-1-LI neurons expressing Fos were significantly increased in the SON, the PVN, the Arc, the LHA, the CAN, the DR, the AP and the NTS, compared with the control group. The pretreatment of nesfatin-1 antisense significantly attenuated this xenin-induced feeding suppression, while that of nesfatin-1 missense showed no improvement. These results indicate that central administered xenin may have anorexia effects associated with activated central nesfatin-1 neurons.
Topics: Humans; Rats; Animals; DNA-Binding Proteins; Nucleobindins; Calcium-Binding Proteins; Neurons
PubMed: 37844783
DOI: 10.1016/j.brainresbull.2023.110788 -
Science (New York, N.Y.) Oct 2023During pregnancy, physiological adaptations prepare the female body for the challenges of motherhood. Becoming a parent also requires behavioral adaptations. Such...
During pregnancy, physiological adaptations prepare the female body for the challenges of motherhood. Becoming a parent also requires behavioral adaptations. Such adaptations can occur as early as during pregnancy, but how pregnancy hormones remodel parenting circuits to instruct preparatory behavioral changes remains unknown. We found that action of estradiol and progesterone on galanin (Gal)-expressing neurons in the mouse medial preoptic area (MPOA) is critical for pregnancy-induced parental behavior. Whereas estradiol silences MPOA neurons and paradoxically increases their excitability, progesterone permanently rewires this circuit node by promoting dendritic spine formation and recruitment of excitatory synaptic inputs. This MPOA-specific neural remodeling sparsens population activity in vivo and results in persistently stronger, more selective responses to pup stimuli. Pregnancy hormones thus remodel parenting circuits in anticipation of future behavioral need.
Topics: Animals; Female; Mice; Pregnancy; Estradiol; Maternal Behavior; Parenting; Preoptic Area; Progesterone; Models, Animal; Neurons
PubMed: 37797007
DOI: 10.1126/science.adi0576 -
Frontiers in Neural Circuits 2023Cortical GABAergic interneurons are critical components of neural networks. They provide local and long-range inhibition and help coordinate network activities involved... (Review)
Review
Cortical GABAergic interneurons are critical components of neural networks. They provide local and long-range inhibition and help coordinate network activities involved in various brain functions, including signal processing, learning, memory and adaptative responses. Disruption of cortical GABAergic interneuron migration thus induces profound deficits in neural network organization and function, and results in a variety of neurodevelopmental and neuropsychiatric disorders including epilepsy, intellectual disability, autism spectrum disorders and schizophrenia. It is thus of paramount importance to elucidate the specific mechanisms that govern the migration of interneurons to clarify some of the underlying disease mechanisms. GABAergic interneurons destined to populate the cortex arise from multipotent ventral progenitor cells located in the ganglionic eminences and pre-optic area. Post-mitotic interneurons exit their place of origin in the ventral forebrain and migrate dorsally using defined migratory streams to reach the cortical plate, which they enter through radial migration before dispersing to settle in their final laminar allocation. While migrating, cortical interneurons constantly change their morphology through the dynamic remodeling of actomyosin and microtubule cytoskeleton as they detect and integrate extracellular guidance cues generated by neuronal and non-neuronal sources distributed along their migratory routes. These processes ensure proper distribution of GABAergic interneurons across cortical areas and lamina, supporting the development of adequate network connectivity and brain function. This short review summarizes current knowledge on the cellular and molecular mechanisms controlling cortical GABAergic interneuron migration, with a focus on tangential migration, and addresses potential avenues for cell-based interneuron progenitor transplants in the treatment of neurodevelopmental disorders and epilepsy.
Topics: Cerebral Cortex; Neurogenesis; Interneurons; Cell Movement
PubMed: 37779671
DOI: 10.3389/fncir.2023.1256455