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Frontiers in Neuroscience 2021The preoptic area of the hypothalamus is a homeostatic control center. The heterogeneous neurons in this nucleus function to regulate the sleep/wake cycle, reproduction,...
The preoptic area of the hypothalamus is a homeostatic control center. The heterogeneous neurons in this nucleus function to regulate the sleep/wake cycle, reproduction, thirst and hydration, as well as thermogenesis and other metabolic responses. Several recent studies have analyzed preoptic neuronal populations and demonstrated neuronal subtype-specific roles in suppression of thermogenesis. These studies showed similar thermogenesis responses to chemogenetic modulation, and similar synaptic tracing patterns for neurons that were responsive to cold, to inflammatory stimuli, and to violet light. A reanalysis of single-cell/nucleus RNA-sequencing datasets of the preoptic nucleus indicate that these studies have converged on a common neuronal population that when activated, are sufficient to suppress thermogenesis. Expanding on a previous name for these neurons (Q neurons, which reflect their ability to promote quiescence and expression of ), we propose a new name: QPLOT neurons, to reflect numerous molecular markers of this population and to capture its broader roles in metabolic regulation. Here, we summarize previous findings on this population and present a unified description of QPLOT neurons, the excitatory preoptic neuronal population that integrate a variety of thermal, metabolic, hormonal and environmental stimuli in order to regulate metabolism and thermogenesis.
PubMed: 34017237
DOI: 10.3389/fnins.2021.665762 -
Cell Reports Aug 2021Enhanced appetite occurs as a means of behavioral thermoregulation at low temperature. Neural circuitry mediating this crosstalk between behavioral thermoregulation and...
Enhanced appetite occurs as a means of behavioral thermoregulation at low temperature. Neural circuitry mediating this crosstalk between behavioral thermoregulation and energy homeostasis remains to be elucidated. We find that the hypothalamic orexigenic agouti-related neuropeptide (AgRP) neurons in the arcuate nucleus (ARC) are profoundly activated by cold exposure. The calcium signals in ARC neurons display an immediate-response pattern in response to cold stimulation. Cold-responsive neurons in the medial preoptic area (mPOA) make excitatory synapses onto ARC neurons. Inhibition of either ARC neurons or ARC-projecting mPOA neurons attenuates cold-evoked feeding, while activation of the mPOA-to-ARC projection increases food intake. These findings reveal an mPOA-ARC neural pathway that modulates cold-evoked feeding behavior.
Topics: Agouti-Related Protein; Animals; Arcuate Nucleus of Hypothalamus; Cold Temperature; Feeding Behavior; Mice, Inbred C57BL; Neural Pathways; Neurons; Preoptic Area; Synapses; Mice
PubMed: 34380037
DOI: 10.1016/j.celrep.2021.109502 -
Frontiers in Neuroscience 2019The lateral preoptic area (LPO) is a hypothalamic region whose function has been largely unexplored. Its direct and indirect projections to the ventral tegmental area...
The lateral preoptic area (LPO) is a hypothalamic region whose function has been largely unexplored. Its direct and indirect projections to the ventral tegmental area (VTA) suggest that the LPO could modulate the activity of the VTA and the reward-related behaviors that the VTA underlies. We examined the role of the LPO on reward taking and seeking using operant self-administration of cocaine or sucrose. Rats were trained to self-administer cocaine or sucrose and then subjected to extinction, whereby responding was no longer reinforced. We tested if stimulating the LPO pharmacologically with bicuculline or chemogenetically with Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) modifies self-administration and/or seeking. In another set of experiments, we tested if manipulating the LPO influences cocaine self-administration during and after punishment. To examine the functional connectivity between the LPO and VTA, we used electrophysiology recordings in anesthetized rats. We tested if stimulating the LPO modifies the activity of GABA and dopamine neurons of the VTA. We found that stimulating the LPO reinstated cocaine and sucrose seeking behavior but had no effect on reward intake. Furthermore, both stimulating and inhibiting the LPO prevented the sustained reduction in cocaine intake seen after punishment. Finally, stimulating the LPO inhibited the activity of VTA GABA neurons while enhancing that of VTA dopamine neurons. These findings indicate that the LPO has the capacity to drive reward seeking, modulate sustained reductions in self-administration following punishment, and regulate the activity of VTA neurons. Taken together, these findings implicate the LPO as a previously overlooked member of the reward circuit.
PubMed: 32009893
DOI: 10.3389/fnins.2019.01433 -
IScience Oct 2021The role of preoptic GABAergic inhibitory neurons was addressed in parenting, anxiety and depression. Pup exposure and forced swimming resulted in similar activation...
The role of preoptic GABAergic inhibitory neurons was addressed in parenting, anxiety and depression. Pup exposure and forced swimming resulted in similar activation pattern in neurons expressing vesicular GABA transporter in the preoptic area with generally stronger labeling and different distributional pattern in females than in males. Chemogenetic stimulation of preoptic GABAergic cells resulted in elevated maternal motivation and caring behavior in females and mothers but aggression toward pups in males. Behavioral effects were the opposite following inhibition of preoptic GABAergic neurons suggesting their physiological relevance. In addition, increased anxiety-like and depression-like behaviors were found following chemogenetic stimulation of the same neurons in females, whereas previous pup exposure increased only anxiety-like behavior suggesting that not the pups, but overstimulation of the cells can lead to depression-like behavior. A sexually dimorphic projection pattern of preoptic GABAergic neurons was also identified, which could mediate sex-dependent parenting and associated emotional behaviors.
PubMed: 34604722
DOI: 10.1016/j.isci.2021.103090 -
Neuropeptides Feb 2023Galanin (GAL) is a 29 amino acid peptide present in the central nervous system (CNS) as well as peripheral tissues in vertebrates. However, the brain distribution...
Galanin (GAL) is a 29 amino acid peptide present in the central nervous system (CNS) as well as peripheral tissues in vertebrates. However, the brain distribution pattern of GAL is understudied in reptiles. The aim of this study was to determine the organization of galaninergic neuronal system in the brain of the gecko Hemidactylus frenatus, a tropical and sub-tropical lizard, using rabbit anti-galanin antibody. In the telencephalon, GAL-ir perikarya and fibres were found in the lateral septal nucleus, but only GAL-ir fibres were observed in the striatum, nucleus accumbens, anterior commissure, nucleus centralis amygdalae, dorsal and medial septal nuclei, nucleus of the diagonal band of Broca and in the optic chiasma. In the preoptic region, a cluster of GAL-ir cells and fibres was observed in the periventricular preoptic area and lateral preoptic area. GAL-ir perikarya and fibres were observed in hypothalamic areas such as the supraoptic nucleus, suprachiasmatic nucleus, paraventricular nucleus, periventricular nucleus of the hypothalamus, infundibular recess nucleus and in the median eminence, whereas GAL-ir fibres were present in the pars distalis of the pituitary gland. In the thalamus, GAL-ir fibres were observed in the dorsomedial, dorsolateral, and medial thalamic nuclei. GAL-ir fibres were also detected in mesencephalic areas such as the optic tectum, torus semicircularis, ventral tegmental area and substantia nigra, brain stem as well as the spinal cord. The organization of GAL-ir cells and fibres throughout the gecko brain suggests several neuroendocrine, neuromodulatory and behavioural functions for GAL in lizards. The study provides new insights into the evolutionarily conserved nature of GAL peptide in squamate reptiles and forms a valuable basis for future comparative studies.
Topics: Animals; Rabbits; Brain; Mesencephalon; Central Nervous System; Peptides; Lizards
PubMed: 36459764
DOI: 10.1016/j.npep.2022.102310 -
Hormones and Behavior Jun 2022Social motivation and reward are dynamic and flexible, shifting adaptively across contexts to meet changing social demands. This is exceptionally apparent when seasonal... (Review)
Review
Social motivation and reward are dynamic and flexible, shifting adaptively across contexts to meet changing social demands. This is exceptionally apparent when seasonal contexts are considered in seasonally breeding songbirds as they cycle from periods of sexual motivation and reward during the breeding season to periods of extreme gregariousness outside the breeding season when non-sexual social interactions gain reward value, motivating birds to form flocks. Here we review evidence demonstrating a key integrative role for the medial preoptic area (mPOA) in the seasonally-appropriate adjustment of behaviors, with seasonal changes in dopamine activity in mPOA adjusting social motivation and changes in opioid activity modifying social reward. Experiments demonstrate that dramatic seasonal fluctuations in steroid hormone concentrations alter patterns of opioid- and dopamine-related protein and gene expression in mPOA to modify social motivation and reward to meet seasonal changes in social demands. These studies of birdsong and seasonality provide new insights into neural and endocrine mechanisms underlying adaptive changes in social motivation and reward and highlight an underappreciated, evolutionarily conserved role for the mPOA in important social behaviors in non-reproductive contexts.
Topics: Analgesics, Opioid; Animals; Dopamine; Motivation; Preoptic Area; Reward; Sexual Behavior, Animal; Starlings; Vocalization, Animal
PubMed: 35313200
DOI: 10.1016/j.yhbeh.2022.105156 -
Journal of Thermal Biology Apr 2023Agmatine is an endogenous biogenic amine that exerts various effects on the central nervous system. The hypothalamic preoptic area (POA, thermoregulatory command...
Agmatine is an endogenous biogenic amine that exerts various effects on the central nervous system. The hypothalamic preoptic area (POA, thermoregulatory command center) has high agmatine immunoreactivity. In this study, in conscious and anesthetized male rats, agmatine microinjection into the POA induced hyperthermic responses associated with increased heat production and locomotor activity. Intra-POA administration of agmatine increased the locomotor activity, the brown adipose tissue temperature and rectum temperature, and induced shivering as demonstrated by increased neck muscle electromyographic activity. However, intra-POA administration of agmatine almost had no impact on the tail temperature of anesthetized rats. Furthermore, there were regional differences in the response to agmatine in the POA. The most effective sites for the microinjection of agmatine to elicit hyperthermic responses were localized in the medial preoptic area (MPA). Agmatine microinjection into the median preoptic nucleus (MnPO) and lateral preoptic nucleus (LPO) had a minimal effect on the mean core temperature. Analysis of the in vitro discharge activity of POA neurons in brain slices when perfused with agmatine showed that agmatine inhibited most warm-sensitive but not temperature-insensitive neurons in the MPA. However, regardless of thermosensitivity, the majority of MnPO and LPO neurons were not responsive to agmatine. The results demonstrated that agmatine injection into the POA of male rats, especially the MPA, induced hyperthermic responses, which may be associated with increased BAT thermogenesis, shivering and locomotor activity by inhibiting warm-sensitive neurons.
Topics: Rats; Male; Animals; Preoptic Area; Agmatine; Body Temperature Regulation; Hypothalamus; Shivering
PubMed: 37055134
DOI: 10.1016/j.jtherbio.2023.103529 -
Nature Communications Nov 2022Therapeutic hypothermia at 32-34 °C during or after cerebral ischaemia is neuroprotective. However, peripheral cold sensor-triggered hypothermia is ineffective and...
Therapeutic hypothermia at 32-34 °C during or after cerebral ischaemia is neuroprotective. However, peripheral cold sensor-triggered hypothermia is ineffective and evokes vigorous counteractive shivering thermogenesis and complications that are difficult to tolerate in awake patients. Here, we show in mice that deep brain stimulation (DBS) of warm-sensitive neurones (WSNs) in the medial preoptic nucleus (MPN) produces tolerable hypothermia. In contrast to surface cooling-evoked hypothermia, DBS mice exhibit a torpor-like state without counteractive shivering. Like hypothermia evoked by chemogenetic activation of WSNs, DBS in free-moving mice elicits a rapid lowering of the core body temperature to 32-34 °C, which confers significant brain protection and motor function reservation. Mechanistically, activation of WSNs contributes to DBS-evoked hypothermia. Inhibition of WSNs prevents DBS-evoked hypothermia. Maintaining the core body temperature at normothermia during DBS abolishes DBS-mediated brain protection. Thus, the MPN is a DBS target to evoke tolerable therapeutic hypothermia for stroke treatment.
Topics: Animals; Mice; Hypothermia; Preoptic Area; Shivering; Brain; Disease Models, Animal; Ischemia
PubMed: 36371436
DOI: 10.1038/s41467-022-34735-2 -
Biological Psychiatry. Cognitive... Jun 2022The goal of this study was to elucidate the fundamental connectivity-resting-state connectivity-within and between nodes in the olfactory and prosocial (PS) cores, which...
BACKGROUND
The goal of this study was to elucidate the fundamental connectivity-resting-state connectivity-within and between nodes in the olfactory and prosocial (PS) cores, which permits the expression of social monogamy in males; and how differential connectivity accounts for differential expression of prosociality and aggression.
METHODS
Using resting-state functional magnetic resonance imaging, we integrated graph theory analysis to compare functional connectivity between two culturally/behaviorally distinct male prairie voles (Microtusochrogaster).
RESULTS
Illinois males display significantly higher levels of prosocial behavior and lower levels of aggression than KI (Kansas dam and Illinois sire) males, which are associated with differences in underlying neural mechanisms and brain microarchitecture. Shared connectivity 1) between the anterior hypothalamic area and the paraventricular nucleus and 2) between the medial preoptic area and bed nucleus of the stria terminalis and the nucleus accumbens core suggests essential relationships required for male prosocial behavior. In contrast, Illinois males displayed higher levels of global connectivity and PS intracore connectivity, a greater role for the bed nucleus of the stria terminalis and anterior hypothalamic area, which were degree connectivity hubs, and greater PS and olfactory intercore connectivity.
CONCLUSIONS
These findings suggest that behavioral differences are associated with PS core degree of connectivity and postsignal induction. This transgenerational system may serve as powerful mental health and drug abuse translational model in future studies.
Topics: Animals; Arvicolinae; Brain; Grassland; Humans; Male; Sexual Behavior, Animal; Social Behavior
PubMed: 34839018
DOI: 10.1016/j.bpsc.2021.11.007 -
Neuropeptides Aug 2023Arginine vasopressin (AVP) plays a hypothermic regulatory role in thermoregulation and is an important endogenous mediator in this mechanism. In the preoptic area (POA),...
Arginine vasopressin (AVP) plays a hypothermic regulatory role in thermoregulation and is an important endogenous mediator in this mechanism. In the preoptic area (POA), AVP increases the spontaneous firing and thermosensitivity of warm-sensitive neurons and decreases those of cold-sensitive and temperature-insensitive neurons. Because POA neurons play a crucial role in precise thermoregulatory responses, these findings indicate that there is an association between the hypothermia and changes in the firing activity of AVP-induced POA neurons. However, the electrophysiological mechanisms by which AVP controls this firing activity remain unclear. Therefore, in the present study, using in vitro hypothalamic brain slices and whole-cell recordings, we elucidated the membrane potential responses of temperature-sensitive and -insensitive POA neurons to identify the applications of AVP or V vasopressin receptor antagonists. By monitoring changes in the resting potential and membrane potential thermosensitivity of the neurons before and during experimental perfusion, we observed that AVP increased the changes in the resting potential of 50% of temperature-insensitive neurons but reduced them in others. These changes are because AVP enhances the membrane potential thermosensitivity of nearly 50% of the temperature-insensitive neurons. On the other hand, AVP changes both the resting potential and membrane potential thermosensitivity of temperature-sensitive neurons, with no differences between the warm- and cold-sensitive neurons. Before and during AVP or V vasopressin receptor antagonist perfusion, no correlation was observed between changes in the thermosensitivity and membrane potential of all neurons. Furthermore, no correlation was observed between the thermosensitivity and membrane potential thermosensitivity of the neurons during experimental perfusion. In the present study, we found that AVP induction did not result in any changes in resting potential, which is unique to temperature-sensitive neurons. The study results suggest that AVP-induced changes in the firing activity and firing rate thermosensitivity of POA neurons are not controlled by resting potentials.
Topics: Rats; Animals; Preoptic Area; Membrane Potentials; Temperature; Arginine Vasopressin; Rats, Sprague-Dawley; Neurons
PubMed: 37148733
DOI: 10.1016/j.npep.2023.102344