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Nature Jun 2022During infection, animals exhibit adaptive changes in physiology and behaviour aimed at increasing survival. Although many causes of infection exist, they trigger...
During infection, animals exhibit adaptive changes in physiology and behaviour aimed at increasing survival. Although many causes of infection exist, they trigger similar stereotyped symptoms such as fever, warmth-seeking, loss of appetite and fatigue. Yet exactly how the nervous system alters body temperature and triggers sickness behaviours to coordinate responses to infection remains unknown. Here we identify a previously uncharacterized population of neurons in the ventral medial preoptic area (VMPO) of the hypothalamus that are activated after sickness induced by lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid. These neurons are crucial for generating a fever response and other sickness symptoms such as warmth-seeking and loss of appetite. Single-nucleus RNA-sequencing and multiplexed error-robust fluorescence in situ hybridization uncovered the identity and distribution of LPS-activated VMPO (VMPO) neurons and non-neuronal cells. Gene expression and electrophysiological measurements implicate a paracrine mechanism in which the release of immune signals by non-neuronal cells during infection activates nearby VMPO neurons. Finally, we show that VMPO neurons exert a broad influence on the activity of brain areas associated with behavioural and homeostatic functions and are synaptically and functionally connected to circuit nodes controlling body temperature and appetite. Together, these results uncover VMPO neurons as a control hub that integrates immune signals to orchestrate multiple sickness symptoms in response to infection.
Topics: Animals; Appetite; Appetite Depressants; Fever; In Situ Hybridization, Fluorescence; Infections; Lipopolysaccharides; Neurons; Paracrine Communication; Poly I-C; Preoptic Area
PubMed: 35676482
DOI: 10.1038/s41586-022-04793-z -
Science (New York, N.Y.) Nov 2018The hypothalamus controls essential social behaviors and homeostatic functions. However, the cellular architecture of hypothalamic nuclei-including the molecular...
The hypothalamus controls essential social behaviors and homeostatic functions. However, the cellular architecture of hypothalamic nuclei-including the molecular identity, spatial organization, and function of distinct cell types-is poorly understood. Here, we developed an imaging-based in situ cell-type identification and mapping method and combined it with single-cell RNA-sequencing to create a molecularly annotated and spatially resolved cell atlas of the mouse hypothalamic preoptic region. We profiled ~1 million cells, identified ~70 neuronal populations characterized by distinct neuromodulatory signatures and spatial organizations, and defined specific neuronal populations activated during social behaviors in male and female mice, providing a high-resolution framework for mechanistic investigation of behavior circuits. The approach described opens a new avenue for the construction of cell atlases in diverse tissues and organisms.
Topics: Animals; Atlases as Topic; Female; Galanin; Gene Expression Profiling; In Situ Hybridization, Fluorescence; Male; Mice; Neurons; Pituitary Adenylate Cyclase-Activating Polypeptide; Preoptic Area; Sequence Analysis, RNA; Single-Cell Analysis; Social Behavior
PubMed: 30385464
DOI: 10.1126/science.aau5324 -
Anatomical Science International Jan 2019The medial preoptic area (MPOA), an anterior part of the hypothalamus, is one of the most important areas for the regulation of instinctively motivated behaviors, such... (Review)
Review
The medial preoptic area (MPOA), an anterior part of the hypothalamus, is one of the most important areas for the regulation of instinctively motivated behaviors, such as parental behavior, mating behavior and aggression. Consistent with its role in reproductive behaviors, the MPOA abundantly expresses gonadal steroid hormone receptors and shows distinct sexual dimorphism in its morphology. Despite the functional importance of the MPOA, the anatomical demarcations of the mouse MPOA subregions have been confusing and remained undefined because of their heterogeneity and complexity. In this review, I first introduce our histological examination showing differential expression of various molecules among the MPOA subregions. I also provide useful molecular markers to delineate the mouse MPOA subregions showing sexual dimorphism. Based on this anatomical study at the subregion level, I also summarize the current understanding of the role of the mouse MPOA and adjacent bed nucleus of the stria terminalis in parental motivation: the central part of the MPOA is essential for parental motivation, and this area exerts an inhibitory effect on the neural activity in the BNST rhomboid nucleus resulting in suppressed infanticide.
Topics: Animals; Behavior, Animal; Biomarkers; Humans; Instinct; Mice; Midline Thalamic Nuclei; Motivation; Neurons; Neuropeptides; Preoptic Area; Sex Characteristics
PubMed: 30392107
DOI: 10.1007/s12565-018-0468-4 -
Nature Jun 2023In many species, including mice, female animals show markedly different pup-directed behaviours based on their reproductive state. Naive wild female mice often kill...
In many species, including mice, female animals show markedly different pup-directed behaviours based on their reproductive state. Naive wild female mice often kill pups, while lactating female mice are dedicated to pup caring. The neural mechanisms that mediate infanticide and its switch to maternal behaviours during motherhood remain unclear. Here, on the basis of the hypothesis that maternal and infanticidal behaviours are supported by distinct and competing neural circuits, we use the medial preoptic area (MPOA), a key site for maternal behaviours, as a starting point and identify three MPOA-connected brain regions that drive differential negative pup-directed behaviours. Functional manipulation and in vivo recording reveal that oestrogen receptor α (ESR1)-expressing cells in the principal nucleus of the bed nucleus of stria terminalis (BNSTpr) are necessary, sufficient and naturally activated during infanticide in female mice. MPOA and BNSTpr neurons form reciprocal inhibition to control the balance between positive and negative infant-directed behaviours. During motherhood, MPOA and BNSTpr cells change their excitability in opposite directions, supporting a marked switch of female behaviours towards the young.
Topics: Animals; Female; Mice; Infanticide; Lactation; Maternal Behavior; Neural Pathways; Preoptic Area; Thalamus
PubMed: 37286598
DOI: 10.1038/s41586-023-06147-9 -
Pharmacology, Biochemistry, and Behavior Jun 2014Several brain nuclei interact to orchestrate the appetitive and consummatory aspects of male sexual behavior. Of these structures, the medial preoptic area (mPOA) of the... (Review)
Review
Several brain nuclei interact to orchestrate the appetitive and consummatory aspects of male sexual behavior. Of these structures, the medial preoptic area (mPOA) of the hypothalamus is of particular interest, as it receives input from all sensory modalities, and damage to this region disrupts copulation in a wide variety of taxa. Furthermore, the mPOA is both responsive to gonadal hormones and involved in endocrine regulation. Neurochemical studies have demonstrated that both dopamine and glutamate levels rise in the mPOA in response to sexual activity, while antagonism of these neurotransmitters impairs male sexual response. Here we review how dopamine and glutamate act in the mPOA to modulate male sexual behavior.
Topics: Animals; Dopamine; Female; Glutamic Acid; Gonadal Steroid Hormones; Male; Models, Neurological; Nitric Oxide; Preoptic Area; Psychopharmacology; Receptors, N-Methyl-D-Aspartate; Sexual Behavior, Animal
PubMed: 24534416
DOI: 10.1016/j.pbb.2014.02.005 -
Physiology & Behavior Oct 2005The medial preoptic area (MPOA), at the rostral end of the hypothalamus, is important for the regulation of male sexual behavior. Results showing that male sexual... (Comparative Study)
Comparative Study Review
The medial preoptic area (MPOA), at the rostral end of the hypothalamus, is important for the regulation of male sexual behavior. Results showing that male sexual behavior is impaired following MPOA lesions and enhanced with MPOA stimulation support this conclusion. The neurotransmitter dopamine (DA) facilitates male sexual behavior in all studied species, including rodents and humans. Here, we review data indicating that the MPOA is one site where DA may act to regulate male sexual behavior. DA agonists microinjected into the MPOA facilitate sexual behavior, whereas DA antagonists impair copulation, genital reflexes, and sexual motivation. Moreover, microdialysis experiments showed increased release of DA in the MPOA as a result of precopulatory exposure to an estrous female and during copulation. DA may remove tonic inhibition in the MPOA, thereby enhancing sensorimotor integration, and also coordinate autonomic influences on genital reflexes. In addition to sensory stimulation, other factors influence the release of DA in the MPOA, including testosterone, nitric oxide, and glutamate. Here we summarize and interpret these data.
Topics: Animals; Dopamine; Humans; Male; Models, Neurological; Motivation; Preoptic Area; Sexual Behavior; Sexual Behavior, Animal; Testosterone
PubMed: 16135375
DOI: 10.1016/j.physbeh.2005.08.006 -
Neurochemistry International May 2007Several studies have shown the importance of the medial preoptic area in the regulation of sleep-wakefulness and of body temperature. The medial preoptic area has a rich... (Review)
Review
Several studies have shown the importance of the medial preoptic area in the regulation of sleep-wakefulness and of body temperature. The medial preoptic area has a rich noradrenergic innervation, coming mostly from the lateral tegmental noradrenergic system. The accumulating evidences show that the noradrenergic afferents to the medial preoptic area are involved in the induction of sleep. This hypnogenic mechanism operates through the postsynaptic alpha1 and alpha2-adrenergic receptors. Noradrenergic afferents are also involved in the thermoregulatory mechanisms, and the activation of these fibers brings about a fall in body temperature. Though the body temperature changes are brought about by the same receptor subtypes as those involved in hypnogenesis, observations suggest the possibility of separate sets of noradrenergic afferents in the medial preoptic area for sleep regulation and thermoregulation. In this review, we present the compelling evidences, which showed that the noradrenergic afferents of the medial preoptic area bring about a fall in body temperature and other thermoregulatory behavioral alterations associated with sleep.
Topics: Animals; Body Temperature Regulation; Humans; Microinjections; Neurons, Afferent; Norepinephrine; Preoptic Area; Receptors, Adrenergic; Sleep; Sympathetic Nervous System
PubMed: 17403554
DOI: 10.1016/j.neuint.2007.02.004 -
Journal of Neuroendocrinology Oct 2014The preoptic area is a well-established centre for the control of maternal behaviour. An intact medial preoptic area (mPOA) is required for maternal responsiveness... (Review)
Review
The preoptic area is a well-established centre for the control of maternal behaviour. An intact medial preoptic area (mPOA) is required for maternal responsiveness because lesion of the area abolishes maternal behaviours. Although hormonal changes in the peripartum period contribute to the initiation of maternal responsiveness, inputs from pups are required for its maintenance. Neurones are activated in different parts of the mPOA in response to pup exposure. In the present review, we summarise the potential inputs to the mPOA of rodent dams from the litter that can activate mPOA neurones. The roles of potential indirect effects through increased prolactin levels, as well as neuronal inputs to the preoptic area, are described. Recent results on the pathway mediating the effects of suckling to the mPOA suggest that neurones containing the neuropeptide tuberoinfundibular peptide of 39 residues in the posterior thalamus are candidates for conveying the suckling information to the mPOA. Although the molecular mechanism through which these inputs alter mPOA neurones to support the maintenance of maternal responding is not yet known, altered gene expression is a likely candidate. Here, we summarise gene expression changes in the mPOA that have been linked to maternal behaviour and explore the idea that chromatin remodelling during mother-infant interactions mediates the long-term alterations in gene expression that sustain maternal responding.
Topics: Animals; Animals, Suckling; Behavior, Animal; Female; Mothers; Preoptic Area
PubMed: 25059569
DOI: 10.1111/jne.12185 -
Frontiers in Neuroendocrinology Jan 1996About 10 years ago, a sexually differentiated nucleus was identified in the preoptic area (POA) of the Japanese quail in the course of studies analyzing the dimorphic... (Review)
Review
About 10 years ago, a sexually differentiated nucleus was identified in the preoptic area (POA) of the Japanese quail in the course of studies analyzing the dimorphic mechanisms involved in the activation of sexual behavior. In this species, males exposed to testosterone copulate while females never show this masculine behavior. The present paper reviews anatomical, neurochemical, and functional data that have been collected since that time about the quail dimorphic nucleus. The medial preoptic nucleus (POM) is significantly larger in adult male than in adult female quail. Its volume is also steroid-sensitive in adulthood: it decreases when circulating levels of testosterone are low (castration, exposure to short-days) and it increases when testosterone levels are high (treatment with testosterone, exposure to long-days). The POM is a necessary and sufficient site of steroid action for the activation of male copulatory behavior. The volumetric difference of the POM results from a difference in the adult hormonal milieu of males and females (activational effect) and is not affected by embryonic treatments that permanently modify sexual behavior (no organizational effects on POM). In contrast, the size of neurons in the dorsolateral part of POM appears to be irreversibly affected by embryonic steroids and this feature is therefore a better correlate of the behavioral sex difference. The POM is characterized by the presence of a wide variety of neurotransmitters, neuropeptides, and receptors. It can, in addition, be specifically distinguished from the surrounding POA by the presence of aromatase-immunoreactive cells, by a high density of alpha 2-adrenergic receptors, and by a dense vasotocinergic innervation. Some of these neurochemical markers of the dimorphic nucleus are themselves modulated by steroids. In particular, the aromatase-immunoreactive cells of the lateral POM appear to be a key target for steroids in the activation of male copulatory behavior. The POM is bidirectionally connected to many brain areas. It receives inputs from a variety of sensory areas and from a number of regulatory areas (e.g., catecholaminergic cell groups). This nucleus also sends outputs to "neurovegetative" centers and to brain regions directly connected to the motor pathways. These connections fully support the role of the POM as an integrative center for the control of male sexual behavior. The available data indicate that there is a high degree of steroid-induced neuronal plasticity in the POM, including changes in neuronal function, in protein synthesis, and in specific inputs. These phenomena can easily be studied in the POM because they are of a large magnitude, they are localized in a specific brain site, and they develop rapidly after exposure to steroids. They are also directly related to a clear functional output, the activation of male sexual behavior. The quail POM therefore constitutes an exceptional model for the analysis of steroid-induced brain plasticity in a functionally relevant context.
Topics: Androgens; Animals; Aromatase; Castration; Coturnix; Estrogens; Female; Male; Preoptic Area; Sex Characteristics; Sexual Behavior, Animal; Steroids
PubMed: 8788569
DOI: 10.1006/frne.1996.0002 -
Annals of the New York Academy of... 1986In conclusion, POA grafts that contain GnRH cell bodies are capable of correcting many of the reproductive deficiencies that are associated with a genetic failure to... (Review)
Review
In conclusion, POA grafts that contain GnRH cell bodies are capable of correcting many of the reproductive deficiencies that are associated with a genetic failure to produce GnRH. The previously infertile animals exhibit steroidogenesis and gametogenesis. Ovulations associated with mating suggest that the grafted GnRH cells are responding to some environmental cues and may be under some regulation by the host brain. Although the grafts contain tissue that may have sexually dimorphic characteristics, the studies with the hpg mice have not yet revealed any effects of the grafts that could be related to the sex of the donor.
Topics: Animals; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Luteinizing Hormone; Male; Maternal Behavior; Mice; Mice, Mutant Strains; Preoptic Area; Reproduction; Sex Characteristics; Sexual Behavior, Animal
PubMed: 3107453
DOI: 10.1111/j.1749-6632.1986.tb27998.x