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Endocrinology Feb 2021Arginine vasopressin (AVP) is a neuropeptide acting as a neuromodulator in the brain and plays multiple roles, including a thermoregulatory one. However, the cellular...
Arginine vasopressin (AVP) is a neuropeptide acting as a neuromodulator in the brain and plays multiple roles, including a thermoregulatory one. However, the cellular mechanisms of action are not fully understood. Carried out are patch clamp recordings and calcium imaging combined with pharmacological tools and single-cell RT-PCR to dissect the signaling mechanisms activated by AVP. Optogenetics combined with patch-clamp recordings were used to determine the neurochemical nature of these neurons. Also used is telemetry combined with chemogenetics to study the effect of activation of AVP neurons in thermoregulatory mechanisms. This article reports that AVP neurons in the medial preoptic (MPO) area release GABA and display thermosensitive firing activity. Their optogenetic stimulation results in a decrease of the firing rates of MPO pituitary adenylate cyclase-activating polypeptide (PACAP) neurons. Local application of AVP potently modulates the synaptic inputs of PACAP neurons, by activating neuronal AVPr1a receptors and astrocytic AVPr1b receptors. Chemogenetic activation of MPO AVP neurons induces hyperthermia. Chemogenetic activation of all AVP neurons in the brain similarly induces hyperthermia and, in addition, decreases the endotoxin activated fever as well as the stress-induced hyperthermia.
Topics: Animals; Arginine Vasopressin; Biological Clocks; Body Temperature Regulation; Calcium; Hyperthermia; Inhibitory Postsynaptic Potentials; Male; Mice, Transgenic; Neurons; Optogenetics; Preoptic Area
PubMed: 33249461
DOI: 10.1210/endocr/bqaa217 -
Communications Biology Aug 2021The preoptic area (POA) is one of the most evolutionarily conserved regions of the vertebrate brain and contains subsets of neuropeptide-expressing neurons. Here we...
The preoptic area (POA) is one of the most evolutionarily conserved regions of the vertebrate brain and contains subsets of neuropeptide-expressing neurons. Here we found in the teleost medaka that two neuropeptides belonging to the secretin family, pituitary adenylate cyclase-activating polypeptide (Pacap) and vasoactive intestinal peptide (Vip), exhibit opposite patterns of sexually dimorphic expression in the same population of POA neurons that project to the anterior pituitary: Pacap is male-biased, whereas Vip is female-biased. Estrogen secreted by the ovary in adulthood was found to attenuate Pacap expression and, conversely, stimulate Vip expression in the female POA, thereby establishing and maintaining their opposite sexual dimorphism. Pituitary organ culture experiments demonstrated that both Pacap and Vip can markedly alter the expression of various anterior pituitary hormones. Collectively, these findings show that males and females use alternative preoptic neuropeptides to regulate anterior pituitary hormones as a result of their different estrogen milieu.
Topics: Animals; Estrogens; Female; Fish Proteins; Male; Neuropeptides; Oryzias; Pituitary Hormones; Preoptic Area; Sex Characteristics
PubMed: 34373576
DOI: 10.1038/s42003-021-02476-5 -
Current Biology : CB Jan 2021Endogenous sleep and general anesthesia are distinct states that share similar traits. Of particular interest to neuroscience is the loss of consciousness that...
Endogenous sleep and general anesthesia are distinct states that share similar traits. Of particular interest to neuroscience is the loss of consciousness that accompanies both states. Multiple lines of evidence demonstrate that general anesthetics can co-opt the neural circuits regulating arousal to produce unconsciousness. However, controversy remains as to whether the neural circuits and, more specifically, the same neurons shaping sleep and wakefulness actually do influence the anesthetic state in vivo. Hypothalamic preoptic area (POA) neurons are intimately involved in modulating spontaneous and anesthetic-induced changes in arousal. Nevertheless, recent work suggests that POA GABAergic or glutamatergic neurons capable of regulating endogenous sleep fail to influence the onset or dissipation of anesthesia. We hypothesized that the POA's broad neuronal diversity could mask convergent roles of a subset of neurons in regulating both arousal and anesthesia. Contrary to a previously published report, we show that chemogenetic activation of POA Tac1 neurons obliterates both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep, strongly consolidating the waking state for hours, even during a period of elevated sleep drive. Moreover, chemogenetic activation of Tac1 POA neurons stabilizes the wake state against both isoflurane- and sevoflurane-induced unconsciousness. Tac1-activated mice display a partial resistance to entering isoflurane anesthesia and a more pronounced ability to exit both isoflurane- and sevoflurane-induced unconscious states. We conclude that POA Tac1 neurons can potently reinforce arousal both against endogenous and drug-induced unconscious states. POA Tac1 neurons thus add causal support for the involvement of arousal-regulating systems in the state of general anesthesia.
Topics: Administration, Inhalation; Anesthesia, Inhalation; Animals; Arousal; Electroencephalography; Female; Isoflurane; Male; Mice; Mice, Transgenic; Neurons; Preoptic Area; Sevoflurane; Sleep; Stereotaxic Techniques; Tachykinins; Unconsciousness; Wakefulness
PubMed: 33188746
DOI: 10.1016/j.cub.2020.10.050 -
Brain Structure & Function Mar 2017Recent selective stimulation and ablation of galanin neurons in the preoptic area of the hypothalamus established their critical role in control of maternal behaviors....
Recent selective stimulation and ablation of galanin neurons in the preoptic area of the hypothalamus established their critical role in control of maternal behaviors. Here, we identified a group of galanin neurons in the anterior commissural nucleus (ACN), and a distinct group in the medial preoptic area (MPA). Galanin neurons in ACN but not the MPA co-expressed oxytocin. We used immunodetection of phosphorylated STAT5 (pSTAT5), involved in prolactin receptor signal transduction, to evaluate the effects of suckling-induced prolactin release and found that 76 % of galanin cells in ACN, but only 12 % in MPA were prolactin responsive. Nerve terminals containing tuberoinfundibular peptide 39 (TIP39), a neuropeptide that mediates effects of suckling on maternal motivation, were abundant around galanin neurons in both preoptic regions. In the ACN and MPA, 89 and 82 % of galanin neurons received close somatic appositions, with an average of 2.9 and 2.6 per cell, respectively. We observed perisomatic innervation of galanin neurons using correlated light and electron microscopy. The connection was excitatory based on the glutamate content of TIP39 terminals demonstrated by post-embedding immunogold electron microscopy. Injection of the anterograde tracer biotinylated dextran amine into the TIP39-expressing posterior intralaminar complex of the thalamus (PIL) demonstrated that preoptic TIP39 fibers originate in the PIL, which is activated by suckling. Thus, galanin neurons in the preoptic area of mother rats are innervated by an excitatory neuronal pathway that conveys suckling-related information. In turn, they can be topographically and neurochemically divided into two distinct cell groups, of which only one is affected by prolactin.
Topics: Animals; Animals, Suckling; Female; Galanin; Glutamic Acid; Maternal Behavior; Neural Pathways; Neurons; Neuropeptides; Oxytocin; Phosphorylation; Preoptic Area; Prolactin; Rats; Rats, Wistar; STAT5 Transcription Factor; Telencephalic Commissures; Thalamus
PubMed: 27300187
DOI: 10.1007/s00429-016-1246-5 -
The Journal of Neuroscience : the... Sep 2009Sympathetic premotor neurons in the rostral medullary raphe (RMR) regulate heat conservation by tail artery vasoconstriction and brown adipose tissue thermogenesis....
Sympathetic premotor neurons in the rostral medullary raphe (RMR) regulate heat conservation by tail artery vasoconstriction and brown adipose tissue thermogenesis. These neurons are a critical relay in the pathway that increases body temperature. However, the origins of the inputs that activate the RMR during cold exposure have not been definitively identified. We investigated the afferents to the RMR that were activated during cold by examining Fos expression in retrogradely labeled neurons after injection of cholera toxin B subunit (CTb) in the RMR. These experiments identified a cluster of Fos-positive neurons in the dorsomedial hypothalamic nucleus and dorsal hypothalamic area (DMH/DHA) with projections to the RMR that may mediate cold-induced elevation of body temperature. Also, neurons in the median preoptic nucleus (MnPO) and dorsolateral preoptic area (DLPO) and in the A7 noradrenergic cell group were retrogradely labeled but lacked Fos expression, suggesting that they may inhibit the RMR. To investigate whether individual or common preoptic neurons project to the RMR and DMH/DHA, we injected CTb into the RMR and Fluorogold into the DMH/DHA. We found that projections from the DLPO and MnPO to the RMR and DMH/DHA emerge from largely separate neuronal populations, indicating they may be differentially regulated. Combined cell-specific lesions of MnPO and DLPO, but not lesions of either one alone, caused baseline hyperthermia. Our data suggest that the MnPO and DLPO provide parallel inhibitory pathways that tonically inhibit the DMH/DHA and the RMR at baseline, and that hyperthermia requires the release of this inhibition from both nuclei.
Topics: Animals; Body Temperature; Body Temperature Regulation; Catecholamines; Cholera Toxin; Cold Temperature; Fever; Hypothalamus; Lipopolysaccharides; Male; Neural Pathways; Neurons; Norepinephrine; Preoptic Area; Proto-Oncogene Proteins c-fos; Raphe Nuclei; Rats; Rats, Sprague-Dawley; Time Factors
PubMed: 19776281
DOI: 10.1523/JNEUROSCI.2643-09.2009 -
Nature Mar 2018Neural circuits for appetites are regulated by both homeostatic perturbations and ingestive behaviour. However, the circuit organization that integrates these internal...
Neural circuits for appetites are regulated by both homeostatic perturbations and ingestive behaviour. However, the circuit organization that integrates these internal and external stimuli is unclear. Here we show in mice that excitatory neural populations in the lamina terminalis form a hierarchical circuit architecture to regulate thirst. Among them, nitric oxide synthase-expressing neurons in the median preoptic nucleus (MnPO) are essential for the integration of signals from the thirst-driving neurons of the subfornical organ (SFO). Conversely, a distinct inhibitory circuit, involving MnPO GABAergic neurons that express glucagon-like peptide 1 receptor (GLP1R), is activated immediately upon drinking and monosynaptically inhibits SFO thirst neurons. These responses are induced by the ingestion of fluids but not solids, and are time-locked to the onset and offset of drinking. Furthermore, loss-of-function manipulations of GLP1R-expressing MnPO neurons lead to a polydipsic, overdrinking phenotype. These neurons therefore facilitate rapid satiety of thirst by monitoring real-time fluid ingestion. Our study reveals dynamic thirst circuits that integrate the homeostatic-instinctive requirement for fluids and the consequent drinking behaviour to maintain internal water balance.
Topics: Animals; Appetite; Drinking; Female; GABAergic Neurons; Glucagon-Like Peptide-1 Receptor; Homeostasis; Instinct; Male; Mice; Neural Pathways; Nitric Oxide Synthase; Preoptic Area; Satiety Response; Subfornical Organ; Thirst; Water-Electrolyte Balance
PubMed: 29489747
DOI: 10.1038/nature25488 -
Brain Structure & Function Mar 2014Ambulatory locomotion in the rodent is robustly activated by unilateral infusions into the basal forebrain of type A gamma-aminobutyric acid receptor antagonists, such... (Comparative Study)
Comparative Study
Ambulatory locomotion in the rodent is robustly activated by unilateral infusions into the basal forebrain of type A gamma-aminobutyric acid receptor antagonists, such as bicuculline and picrotoxin. The present study was carried out to better localize the neuroanatomical substrate(s) underlying this effect. To accomplish this, differences in total locomotion accumulated during a 20-min test period following bicuculline versus saline infusions in male Sprague-Dawley rats were calculated, rank ordered and mapped on a diagram of basal forebrain transposed from immunoprocessed sections. The most robust locomotor activation was elicited by bicuculline infusions clustered in rostral parts of the preoptic area. Unilateral infusions of bicuculline into the ventral pallidum produced an unanticipatedly diminutive activation of locomotion, which led us to evaluate bilateral ventral pallidal infusions, and these also produced only a small activation of locomotion, and, interestingly, a non-significant trend toward suppression of rearing. Subjects with bicuculline infused bilaterally into the ventral pallidum also exhibited persistent bouts of abnormal movements. Bicuculline infused unilaterally into other forebrain structures, including the bed nucleus of stria terminalis, caudate-putamen, globus pallidus, sublenticular extended amygdala and sublenticular substantia innominata, did not produce significant locomotor activation. Our data identify the rostral preoptic area as the main substrate for the locomotor-activating effects of basal forebrain bicuculline infusions. In contrast, slight activation of locomotion and no effect on rearing accompanied unilateral and bilateral ventral pallidal infusions. Implications of these findings for forebrain processing of reward are discussed.
Topics: Animals; Bicuculline; Brain Mapping; Calbindin 1; Functional Laterality; GABA-A Receptor Antagonists; Gene Expression Regulation; Globus Pallidus; Humans; Male; Motor Activity; Nerve Tissue Proteins; Nitric Oxide Synthase; Parvalbumins; Preoptic Area; Rats; Rats, Sprague-Dawley
PubMed: 23423460
DOI: 10.1007/s00429-013-0514-x -
Cell Metabolism Jul 2021Recent studies have shown that the median preoptic area contains a population of neurons expressing an array of fast neurotransmitters and receptors that collectively...
Recent studies have shown that the median preoptic area contains a population of neurons expressing an array of fast neurotransmitters and receptors that collectively cause a fall in body temperature in response to environmental warming or depleted energy stores. In this issue of Cell Metabolism, Piñol et al. (2021) identify a separate population of median preoptic neurons that are responsible for cold defense and cause stress-related hyperthermia.
Topics: Body Temperature; Body Temperature Regulation; Cold Temperature; Heating; Neurons; Preoptic Area
PubMed: 34233168
DOI: 10.1016/j.cmet.2021.06.010 -
Advances in Experimental Medicine and... 2013Our understanding of kisspeptin and its actions depends, in part, on a detailed knowledge of the neuroanatomy of the kisspeptin signaling system in the brain. In this... (Comparative Study)
Comparative Study Review
Our understanding of kisspeptin and its actions depends, in part, on a detailed knowledge of the neuroanatomy of the kisspeptin signaling system in the brain. In this chapter, we will review our current knowledge of the distribution of kisspeptin cells, fibers, and receptors in the mammalian brain, including the development, phenotype, and projections of different kisspeptin subpopulations. A fairly consistent picture emerges from this analysis. There are two major groups of kisspeptin cell bodies: a large number in the arcuate nucleus (ARC) and a smaller collection in the rostral periventricular area of the third ventricle (RP3V) of rodents and preoptic area (POA) of non-rodents. Both sets of neurons project to GnRH cell bodies, which contain Kiss1r, and the ARC kisspeptin population also projects to GnRH axons in the median eminence. ARC kisspeptin neurons contain neurokinin B and dynorphin, while a variable percentage of those cells in the RP3V of rodents contain galanin and/or dopamine. Neurokinin B and dynorphin have been postulated to contribute to the control of GnRH pulses and sex steroid negative feedback, while the role of galanin and dopamine in rostral kisspeptin neurons is not entirely clear. Kisspeptin neurons, fibers, and Kiss1r are found in other areas, including widespread areas outside the hypothalamus, but their physiological role(s) in these regions remains to be determined.
Topics: Animals; Arcuate Nucleus of Hypothalamus; Axons; Dynorphins; Galanin; Gonadotropin-Releasing Hormone; Humans; Kisspeptins; Neurokinin B; Preoptic Area; Receptors, G-Protein-Coupled; Receptors, Kisspeptin-1; Signal Transduction; Third Ventricle
PubMed: 23550001
DOI: 10.1007/978-1-4614-6199-9_3 -
The Journal of Physiology Jun 19791. Electrophysiological experiments have been performed on intact cycling female rats to investigate the neural connexions that exist between the medial forebrain...
1. Electrophysiological experiments have been performed on intact cycling female rats to investigate the neural connexions that exist between the medial forebrain bundle, the anterior hypothalamic region, which included the preoptic area, and the basal hypothalamus. Recordings have been made from a total of 351 neurones in the anterior hypothalamus of which 216 were responsive to stimulation of either or both the medial forebrain bundle and basal hypothalamus (arcuate and ventromedial nuclei).2. Forty-six of these cells were responsive to a stimulus applied both to the medial forebrain bundle and the basal hypothalamus with a variety of response combinations. The majority of neurones were orthodromically activated by stimulation in both sites. Inhibition by stimulation of the medial forebrain bundle coupled with orthodromic excitation from the basal hypothalamus, or the reverse situation, was also encountered frequently.3. A few cells were antidromically invaded by the stimulation of the medial forebrain bundle and these received orthodromic or inhibitory inputs from the basal hypothalamus, although one unit outside the anterior hypothalamus was antidromically activated by both stimuli.4. Ninety per cent of all the doubly responsive units that could be antidromically activated by stimulation of the basal hypothalamus received an orthodromic input from the medial forebrain bundle, and no cells in the anterior hypothalamus that projected to the basal hypothalamus were found to receive an inhibitory input from the medial forebrain bundle.5. These results provide electrophysiological evidence for inhibitory and excitatory inputs from the medial forebrain bundle to the preoptic and anterior hypothalamic cells that either project to, or receive connexions from, the basal hypothalamus. Neurones in the preoptic area which project to the basal hypothalamus are implicated in the control of anterior pituitary function, particularly gonadotrophin secretion. These experiments, coupled with functional studies, suggest that there is an excitatory input from the medial forebrain bundle to these preoptic and anterior hypothalamic cells which may modulate adenohypophyseal secretions.
Topics: Animals; Evoked Potentials; Female; Hypothalamus; Hypothalamus, Anterior; Medial Forebrain Bundle; Neural Inhibition; Neural Pathways; Neurons; Preoptic Area; Rats
PubMed: 314513
DOI: 10.1113/jphysiol.1979.sp012824