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The Journal of Neuroscience : the... Nov 2023The medial preoptic area (MPOA) is a sexually dimorphic region of the brain that regulates social behaviors. The sexually dimorphic nucleus (SDN) of the MPOA has been...
Two-Step Actions of Testicular Androgens in the Organization of a Male-Specific Neural Pathway from the Medial Preoptic Area to the Ventral Tegmental Area for Modulating Sexually Motivated Behavior.
The medial preoptic area (MPOA) is a sexually dimorphic region of the brain that regulates social behaviors. The sexually dimorphic nucleus (SDN) of the MPOA has been studied to understand sexual dimorphism, although the anatomy and physiology of the SDN is not fully understood. Here, we characterized SDN neurons that contribute to sexual dimorphism and investigated the mechanisms underlying the emergence of such neurons and their roles in social behaviors. A target-specific neuroanatomical study using transgenic mice expressing Cre recombinase under the control of , a gene expressed abundantly in the SDN, revealed that SDN neurons are divided into two subpopulations, GABA neurons projecting to the ventral tegmental area (VTA), where they link to the dopamine system (Calb neurons), and GABA neurons that extend axons in the MPOA or project to neighboring regions (Calb neurons). Calb neurons were abundant in males, but were scarce or absent in females. There was no difference in the number of Calb neurons between sexes. Additionally, we found that emergence of Calb neurons requires two testicular androgen actions that occur first in the postnatal period and second in the peripubertal period. Chemogenetic analyses of Calb neurons indicated a role in modulating sexual motivation in males. Knockdown of in the MPOA reduced the intromission required for males to complete copulation. These findings provide strong evidence that a male-specific neural pathway from the MPOA to the VTA is organized by the two-step actions of testicular androgens for the modulation of sexually motivated behavior. The MPOA is a sexually dimorphic region of the brain that regulates social behaviors, although its sexual dimorphism is not fully understood. Here, we describe a population of MPOA neurons that contribute to the sexual dimorphism. These neurons only exist in masculinized brains, and they project their axons to the ventral tegmental area, where they link to the dopamine system. Emergence of such neurons requires two testicular androgen actions that occur first in the postnatal period and second in the peripubertal period. These MPOA neurons endow masculinized brains with a neural pathway from the MPOA to the ventral tegmental area and modulate sexually motivated behavior in males.
Topics: Animals; Mice; Female; Male; Preoptic Area; Androgens; Ventral Tegmental Area; Dopamine; Neural Pathways; Mice, Transgenic
PubMed: 37722849
DOI: 10.1523/JNEUROSCI.0361-23.2023 -
Current Biology : CB Jan 2024Sleep disturbances are detrimental to our behavioral and emotional well-being. Stressful events disrupt sleep, in particular by inducing brief awakenings (microarousals,...
Sleep disturbances are detrimental to our behavioral and emotional well-being. Stressful events disrupt sleep, in particular by inducing brief awakenings (microarousals, MAs), resulting in sleep fragmentation. The preoptic area of the hypothalamus (POA) is crucial for sleep control. However, how POA neurons contribute to the regulation of MAs and thereby impact sleep quality is unknown. Using fiber photometry in mice, we examine the activity of genetically defined POA subpopulations during sleep. We find that POA glutamatergic neurons are rhythmically activated in synchrony with an infraslow rhythm in the spindle band of the electroencephalogram during non-rapid eye movement sleep (NREMs) and are transiently activated during MAs. Optogenetic stimulation of these neurons promotes MAs and wakefulness. Exposure to acute social defeat stress fragments NREMs and significantly increases the number of transients in the calcium activity of POA glutamatergic neurons during NREMs. By reducing MAs, optogenetic inhibition during spontaneous sleep and after stress consolidates NREMs. Monosynaptically restricted rabies tracing reveals that POA glutamatergic neurons are innervated by brain regions regulating stress and sleep. In particular, presynaptic glutamatergic neurons in the lateral hypothalamus become activated after stress, and stimulating their projections to the POA promotes MAs and wakefulness. Our findings uncover a novel circuit mechanism by which POA excitatory neurons regulate sleep quality after stress.
Topics: Mice; Animals; Sleep Deprivation; Sleep; Hypothalamus; Preoptic Area; Neurons; Wakefulness
PubMed: 38096820
DOI: 10.1016/j.cub.2023.11.035 -
Obesity (Silver Spring, Md.) Nov 2022Elevation of energy expenditure through an increase of brown adipose tissue (BAT) thermogenesis is regarded as one of the most promising ways to prevent obesity...
OBJECTIVE
Elevation of energy expenditure through an increase of brown adipose tissue (BAT) thermogenesis is regarded as one of the most promising ways to prevent obesity development. The preoptic area (POA) of the hypothalamus is a critical area for control of BAT thermogenesis. However, the intracellular signaling cascades in the POA for regulation of BAT thermogenesis are poorly understood.
METHODS
Phosphorylation proteomics (phosphoproteomics) and bioinformatics approaches were used to disclose numerous hypothalamic signaling pathways involved in the regulation of BAT thermogenesis. Conditional manipulation of the p38α gene in mouse POA was performed by stereotaxic injection of adeno-associated virus 9 vector to explore the role of p38α in BAT thermogenesis.
RESULTS
Multiple hypothalamic signaling pathways were triggered by cold exposure, especially the mitogen-activated protein kinase (MAPK) signaling pathway. The p38α activation, but not extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun NH2-terminal kinase (JNK), in the hypothalamus was significantly decreased during cold exposure. p38α deficiency in the POA dramatically elevated energy expenditure owing to a marked increase in BAT thermogenesis, resulting in significantly decreased body weight gain and fat mass. Overexpression of p38α in the POA led to a dramatic increase in weight gain.
CONCLUSIONS
These results demonstrate that p38α in the POA exacerbates obesity development, at least in part owing to a decrease in BAT thermogenesis.
Topics: Mice; Animals; Adipose Tissue, Brown; Preoptic Area; Thermogenesis; Obesity; Energy Metabolism; Weight Gain
PubMed: 36321273
DOI: 10.1002/oby.23552 -
Brain Structure & Function Dec 2019The median preoptic nucleus (MnPO) and the ventrolateral preoptic nucleus (VLPO) are two brain structures that contain neurons essential for promoting non-rapid eye...
The median preoptic nucleus (MnPO) and the ventrolateral preoptic nucleus (VLPO) are two brain structures that contain neurons essential for promoting non-rapid eye movement (NREM) sleep. However, their connections are still largely unknown. Here, we describe for the first time a slice preparation with an oblique coronal slicing angle at 70° from the horizontal in which their connectivity is preserved. Using the in vivo iDISCO method following viral infection of the MnPO or ex vivo biocytin crystal deposition in the MnPO of mouse brain slices, we revealed a strong axonal pathway from the MnPO to the VLPO. Then, to further explore the functionality of these projections, acute 70° slices were placed on multielectrode arrays (MEAs) and electrical stimulations were performed near the MnPO. Recordings of the signals propagation throughout the slices revealed a preferential pathway from the MnPO to the VLPO. Finally, we performed an input-output curve of field responses evoked by stimulation of the MnPO and recorded in the VLPO. We found that field responses were inhibited by GABA receptor antagonist, suggesting that afferent inputs from the MnPO activate VLPO neuronal networks by disinhibition.
Topics: Animals; Axons; Male; Mice, Inbred C57BL; Neural Pathways; Neuroanatomical Tract-Tracing Techniques; Neurons; Preoptic Area
PubMed: 31493023
DOI: 10.1007/s00429-019-01935-4 -
Handbook of Clinical Neurology 2021Located in the midline lamina terminalis of the anterior wall of the third ventricle, the median preoptic nucleus is a thin elongated nucleus stretching around the... (Review)
Review
Located in the midline lamina terminalis of the anterior wall of the third ventricle, the median preoptic nucleus is a thin elongated nucleus stretching around the rostral border of the anterior commissure. Its neuronal elements, composed of various types of excitatory glutamatergic and inhibitory GABAergic neurons, receive afferent neural signals from (1) neighboring subfornical organ and organum vasculosum of the lamina terminalis related to plasma osmolality and hormone concentrations, e.g., angiotensin II; (2) from peripheral sensors such as arterial baroreceptors and cutaneous thermosensors. Different sets of these MnPO glutamatergic and GABAergic neurons relay output signals to hypothalamic, midbrain, and medullary regions that drive homeostatic effector responses. Included in the effector responses are (1) thirst, antidiuretic hormone secretion and renal sodium excretion that subserve osmoregulation and body fluid homeostasis; (2) vasoconstriction or dilatation of skin blood vessels, and shivering and brown adipose tissue thermogenesis for core temperature homeostasis; (3) inhibition of hypothalamic and midbrain nuclei that stimulate wakefulness and arousal, thereby promoting both REM and non-REM sleep; and (4) activation of sympathetic pathways that drive vasoconstriction and heart rate to maintain arterial pressure and the perfusion of vital organs. The small size of MnPO belies its massive homeostatic significance.
Topics: GABAergic Neurons; Homeostasis; Humans; Preoptic Area; Sleep; Temperature
PubMed: 34225980
DOI: 10.1016/B978-0-12-819975-6.00028-5 -
Acta Physiologica (Oxford, England) May 2015Located in the midline anterior wall of the third cerebral ventricle (i.e. the lamina terminalis), the median preoptic nucleus (MnPO) receives a unique set of afferent... (Review)
Review
Located in the midline anterior wall of the third cerebral ventricle (i.e. the lamina terminalis), the median preoptic nucleus (MnPO) receives a unique set of afferent neural inputs from fore-, mid- and hindbrain. These afferent connections enable it to receive neural signals related to several important aspects of homeostasis. Included in these afferent projections are (i) neural inputs from two adjacent circumventricular organs, the subfornical organ and organum vasculosum laminae terminalis, that respond to hypertonicity, circulating angiotensin II or other humoural factors, (ii) signals from cutaneous warm and cold receptors that are relayed to MnPO, respectively, via different subnuclei in the lateral parabrachial nucleus and (iii) input from the medulla associated with baroreceptor and vagal afferents. These afferent signals reach appropriate neurones within the MnPO that enable relevant neural outputs, both excitatory and inhibitory, to be activated or inhibited. The efferent neural pathways that proceed from the MnPO terminate on (i) neuroendocrine cells in the hypothalamic supraoptic and paraventricular nuclei to regulate vasopressin release, while polysynaptic pathways from MnPO to cortical sites may drive thirst and water intake, (ii) thermoregulatory pathways to the dorsomedial hypothalamic nucleus and medullary raphé to regulate shivering, brown adipose tissue and skin vasoconstriction, (iii) parvocellular neurones in the hypothalamic paraventricular nucleus that drive autonomic pathways influencing cardiovascular function. As well, (iv) other efferent pathways from the MnPO to sites in the ventrolateral pre-optic nucleus, perifornical region of the lateral hypothalamic area and midbrain influence sleep mechanisms.
Topics: Animals; Body Fluids; Body Temperature Regulation; Cardiovascular Physiological Phenomena; Homeostasis; Humans; Preoptic Area; Sleep; Sodium
PubMed: 25753944
DOI: 10.1111/apha.12487 -
Neuron Apr 2018In this issue of Neuron, Fang et al. (2018) identified a neural circuit that connects the medial preoptic area to the ventral tegmental area as a critical pathway for...
In this issue of Neuron, Fang et al. (2018) identified a neural circuit that connects the medial preoptic area to the ventral tegmental area as a critical pathway for pup retrieval in female mice.
Topics: Animals; Female; Humans; Maternal Behavior; Mice; Neurons; Preoptic Area; Ventral Tegmental Area
PubMed: 29621491
DOI: 10.1016/j.neuron.2018.03.025 -
General and Comparative Endocrinology Mar 2023In the catfish Heteropneustes fossilis, three nonapeptide hormone genes were identified in the brain preoptic area (POA) and ovary: a pro-vasotocin (pro-vt) and two...
In the catfish Heteropneustes fossilis, three nonapeptide hormone genes were identified in the brain preoptic area (POA) and ovary: a pro-vasotocin (pro-vt) and two isotocin gene paralogs viz., a novel pro-ita and conventional pro-itb. In the present study, the regulatory role of catecholamines [CA: dopamine (DA), noradrenaline (NA), adrenaline (AD)] on the expression of these genes were investigated in vitro. DA (1, 10, and 100 ng/mL) inhibited significantly the mRNA expression in both the POA and ovary. NA upregulated the POA mRNA expression in a biphasic manner, the lower concentrations (1 ng and 10 ng) scaled up and the higher concentration (100 ng) scaled down the expression of pro-vt and pro-itb, while only the 1 ng NA scaled up the pro-ita expression. In the ovary, NA upregulated the mRNA expressions at all concentrations; the pro-vt expression was stimulated only at 10 and 100 ng. AD stimulated pro-vt and pro-ita expression in the POA at all concentrations but the pro-itb expression was inhibited at 1 and 10 ng, and stimulated at 100 ng concentrations. In the ovary, AD elicited varied effects; no significant change in pro-vt, a stimulation of pro-ita, and an inhibition of pro-itb at 1 ng, and stimulation of pro-itb at the 10 and 100 ng. The incubation of the POA and ovary with α-methylparatyrosine (MPT, 250 µg/mL, a tyrosine hydroxylase inhibitor) for 8 h downregulated the mRNA expression in the POA but unaltered the expression in the ovary. Pre-incubation with MPT for 4 h, followed by co-incubation with DA, NA or AD for 4 h elicited varied effects. In the POA, the co-incubations with the CAs rescued the inhibition due to MPT. The MPT + DA and MPT + AD treatments reduced the magnitude of the inhibition of pro-vt and pro-itb by MPT. But the pro-ita expression was modestly stimulated in the MPT + AD group. On the other hand, the MPT + NA treatment rescued the MPT effect and elicited 10-folds increase in the expression levels. In the ovary, the changes were: an inhibition in the MPT + DA group, no significant alteration in the MPT + NA group, and a mild stimulation in the MPT + AD group. The results suggest that CAs modulate brain and ovarian nonapeptide gene expression differentially, which is important in the neuroendocrine/endocrine integration of reproduction in the catfish.
Topics: Animals; Female; Catecholamines; Ovary; Preoptic Area; Catfishes; Norepinephrine; Epinephrine; Dopamine; Vasotocin; RNA, Messenger
PubMed: 36642230
DOI: 10.1016/j.ygcen.2023.114211 -
Cell Reports Jun 2021Maternal mammals exhibit heightened motivation to care for offspring, but the underlying neuromolecular mechanisms have yet to be clarified. Here, we report that the...
Maternal mammals exhibit heightened motivation to care for offspring, but the underlying neuromolecular mechanisms have yet to be clarified. Here, we report that the calcitonin receptor (Calcr) and its ligand amylin are expressed in distinct neuronal populations in the medial preoptic area (MPOA) and are upregulated in mothers. Calcr+ MPOA neurons activated by parental care project to somatomotor and monoaminergic brainstem nuclei. Retrograde monosynaptic tracing reveals that significant modification of afferents to Calcr+ neurons occurs in mothers. Knockdown of either Calcr or amylin gene expression hampers risk-taking maternal care, and specific silencing of Calcr+ MPOA neurons inhibits nurturing behaviors, while pharmacogenetic activation prevents infanticide in virgin males. These data indicate that Calcr+ MPOA neurons are required for both maternal and allomaternal nurturing behaviors and that upregulation of amylin-Calcr signaling in the MPOA at least partially mediates risk-taking maternal care, possibly via modified connectomics of Calcr+ neurons postpartum.
Topics: Animals; Behavior, Animal; Estrogens; Female; Gene Silencing; Gene Targeting; Islet Amyloid Polypeptide; Lactation; Ligands; Male; Maternal Behavior; Mice, Inbred C57BL; Neurons; Postpartum Period; Preoptic Area; Prolactin; Receptors, Calcitonin; Risk-Taking; Signal Transduction; Synapses; Up-Regulation; Mice
PubMed: 34077719
DOI: 10.1016/j.celrep.2021.109204 -
PloS One 2020The lateral hypothalamus (LH) includes several anatomical subregions involved in eating and reward motivation. This study explored localization of function across...
The lateral hypothalamus (LH) includes several anatomical subregions involved in eating and reward motivation. This study explored localization of function across different LH subregions in controlling food intake stimulated by optogenetic channelrhodopsin excitation, and in supporting laser self-stimulation. We particularly compared the tuberal LH subregion, the posterior LH subregion, and the lateral preoptic area. Local diameters of tissue optogenetically stimulated within the LH were assessed by measuring laser-induced Fos plumes and Jun plumes via immunofluorescence surrounding optic fiber tips. Those plume diameters were used to map localization of function for behavioral effects elicited by LH optogenetic stimulation. Optogenetic stimulation of the tuberal subsection of the LH produced the most robust eating behavior and food intake initially, but produced only mild laser self-stimulation in the same rats. However, after repeated exposures to optogenetic stimulation, tuberal LH behavioral profiles shifted toward more self-stimulation and less food intake. By contrast, stimulation of the lateral preoptic area produced relatively little food intake or self-stimulation, either initially or after extended stimulation experience. Stimulation in the posterior LH subregion supported moderate self-stimulation, but not food intake, and at higher laser intensity shifted valence to evoke escape behaviors. We conclude that the tuberal LH subregion may best mediate stimulation-bound increases in food intake stimulated by optogenetic excitation. However, incentive motivational effects of tuberal LH stimulation may shift toward self-stimulation behavior after repeated stimulation. By contrast, the lateral preoptic area and posterior LH do not as readily elicit either eating behavior or laser self-stimulation, and may be more prone to higher-intensity aversive effects.
Topics: Animals; Electric Stimulation; Feeding Behavior; Hypothalamic Area, Lateral; Motivation; Optogenetics; Preoptic Area; Rats; Reward; Self Stimulation
PubMed: 31986148
DOI: 10.1371/journal.pone.0224301