-
CNS Neuroscience & Therapeutics May 2024The preoptic area (POA) of the hypothalamus, crucial in thermoregulation, has long been implicated in the pain process. However, whether nociceptive stimulation affects...
AIMS
The preoptic area (POA) of the hypothalamus, crucial in thermoregulation, has long been implicated in the pain process. However, whether nociceptive stimulation affects body temperature and its mechanism remains poorly studied.
METHODS
We used capsaicin, formalin, and surgery to induce acute nociceptive stimulation and monitored rectal temperature. Optical fiber recording, chemical genetics, confocal imaging, and pharmacology assays were employed to confirm the role and interaction of POA astrocytes and extracellular adenosine. Immunofluorescence was utilized for further validation.
RESULTS
Acute nociception could activate POA astrocytes and induce a decrease in body temperature. Manipulation of astrocytes allowed bidirectional control of body temperature. Furthermore, acute nociception and astrocyte activation led to increased extracellular adenosine concentration within the POA. Activation of adenosine A1 or A2A receptors contributed to decreased body temperature, while inhibition of these receptors mitigated the thermo-lowering effect of astrocytes.
CONCLUSION
Our results elucidate the interplay between acute nociception and thermoregulation, specifically highlighting POA astrocyte activation. This enriches our understanding of physiological responses to painful stimuli and contributes to the analysis of the anatomical basis involved in the process.
Topics: Animals; Preoptic Area; Astrocytes; Nociception; Hypothermia; Male; Mice; Receptors, Purinergic P1; Mice, Inbred C57BL; Adenosine; Capsaicin; Formaldehyde
PubMed: 38715251
DOI: 10.1111/cns.14726 -
Proceedings of the National Academy of... Mar 2023The sexually dimorphic nucleus of the preoptic area (SDN-POA) is the oldest and most robust sex difference reported in mammalian brain and is singular for its presence...
The sexually dimorphic nucleus of the preoptic area (SDN-POA) is the oldest and most robust sex difference reported in mammalian brain and is singular for its presence across a wide range of species from rodents to ungulates to man. This small collection of Nissl-dense neurons is reliably larger in volume in males. Despite its notoriety and intense interrogation, both the mechanism establishing the sex difference and the functional role of the SDN have remained elusive. Convergent evidence from rodent studies led to the conclusion that testicular androgens aromatized to estrogens are neuroprotective in males and that higher apoptosis (naturally occurring cell death) in females determines their smaller SDN. In several species, including humans, a smaller SDN correlates with a preference for mating with males. We report here that this volume difference is dependent upon a participatory role of phagocytic microglia which engulf more neurons in the female SDN and assure their destruction. Selectively blocking microglia phagocytosis temporarily spared neurons from apoptotic death and increased SDN volume in females without hormone treatment. Increasing the number of neurons in the SDN in neonatal females resulted in loss of preference for male odors in adulthood, an effect paralleled by dampened excitation of SDN neurons as evidenced by reduced immediate early gene (IEG) expression when exposed to male urine. Thus, the mechanism establishing a sex difference in SDN volume includes an essential role for microglia, and SDN function as a regulator of sexual partner preference is confirmed.
Topics: Humans; Rats; Female; Male; Animals; Microglia; Preoptic Area; Sexual Behavior; Reproduction; Phagocytosis; Mammals
PubMed: 36848562
DOI: 10.1073/pnas.2212646120 -
Molecular and Cellular Endocrinology May 2018Testosterone (T) can act directly through neural androgen receptors (AR) to facilitate male sexual behavior; however, T's metabolites also can play complicated and... (Review)
Review
Testosterone (T) can act directly through neural androgen receptors (AR) to facilitate male sexual behavior; however, T's metabolites also can play complicated and interesting roles in the control of mating. One metabolite, dihydrotestosterone (DHT) binds to AR with significantly greater affinity than that of T. Is that important behaviorally? Another metabolite, estradiol (E), offers a potential alternative route of facilitating male mating behavior by acting through estradiol receptors (ER). In this review we explore the roles and relative importance of T as well as E and DHT at various levels of the neuroaxis for the activation of male sex behavior in common laboratory animals and, when relevant research findings are available, in man.
Topics: Animals; Autonomic Nervous System; Hormones; Humans; Lumbar Vertebrae; Male; Preoptic Area; Sexual Behavior; Stress, Psychological
PubMed: 29100889
DOI: 10.1016/j.mce.2017.10.018 -
Cell and Tissue Research Jan 2019The paraventricular nucleus (PVN) of the hypothalamus harbors diverse neurosecretory cells with critical physiological roles for the homeostasis. Decades of research in... (Review)
Review
The paraventricular nucleus (PVN) of the hypothalamus harbors diverse neurosecretory cells with critical physiological roles for the homeostasis. Decades of research in rodents have provided a large amount of information on the anatomy, development, and function of this important hypothalamic nucleus. However, since the hypothalamus lies deep within the brain in mammals and is difficult to access, many questions regarding development and plasticity of this nucleus still remain. In particular, how different environmental conditions, including stress exposure, shape the development of this important nucleus has been difficult to address in animals that develop in utero. To address these open questions, the transparent larval zebrafish with its rapid external development and excellent genetic toolbox offers exciting opportunities. In this review, we summarize recent information on the anatomy and development of the neurosecretory preoptic area (NPO), which represents a similar structure to the mammalian PVN in zebrafish. We will then review recent studies on the development of different cell types in the neurosecretory hypothalamus both in mouse and in fish. Lastly, we discuss stress-induced plasticity of the PVN mainly discussing the data obtained in rodents, but pointing out tools and approaches available in zebrafish for future studies. This review serves as a primer for the currently available information relevant for studying the development and plasticity of this important brain region using zebrafish.
Topics: Animals; Hypothalamus; Neuronal Plasticity; Neurosecretory Systems; Preoptic Area; Stress, Physiological; Zebrafish
PubMed: 30109407
DOI: 10.1007/s00441-018-2900-4 -
Current Biology : CB Nov 2022Social touch is an essential component of communication. Little is known about the underlying pathways and mechanisms. Here, we discovered a novel neuronal pathway from...
Social touch is an essential component of communication. Little is known about the underlying pathways and mechanisms. Here, we discovered a novel neuronal pathway from the posterior intralaminar thalamic nucleus (PIL) to the medial preoptic area (MPOA) involved in the control of social grooming. We found that the neurons in the PIL and MPOA were naturally activated by physical contact between female rats and also by the chemogenetic stimulation of PIL neurons. The activity-dependent tagging of PIL neurons was performed in rats experiencing physical social contact. The chemogenetic activation of these neurons increased social grooming between familiar rats, as did the selective activation of the PIL-MPOA pathway. Neurons projecting from the PIL to the MPOA express the neuropeptide parathyroid hormone 2 (PTH2), and the central infusion of its receptor antagonist diminished social grooming. Finally, we showed a similarity in the anatomical organization of the PIL and the distribution of the PTH2 receptor in the MPOA between the rat and human brain. We propose that the discovered neuronal pathway facilitates physical contact with conspecifics.
Topics: Humans; Rats; Female; Animals; Grooming; Rodentia; Preoptic Area; Neurons; Neuropeptides
PubMed: 36113471
DOI: 10.1016/j.cub.2022.08.062 -
The Journal of Neuroscience : the... May 2020Male animals may show alternative behaviors toward infants: attack or parenting. These behaviors are triggered by pup stimuli under the influence of the internal state,...
Male animals may show alternative behaviors toward infants: attack or parenting. These behaviors are triggered by pup stimuli under the influence of the internal state, including the hormonal environment and/or social experiences. Converging data suggest that the medial preoptic area (MPOA) contributes to the behavioral selection toward the pup. However, the neural mechanisms underlying how integrated stimuli affect the MPOA-dependent behavioral selection remain unclear. Here we focus on the amygdalohippocampal area (AHi) that projects to MPOA and expresses oxytocin receptor, a hormone receptor mediating social behavior toward pups. We describe the activation of MPOA-projection AHi neurons in male mice by social contact with pups. Input mapping using the TRIO method reveals that MPOA-projection AHi neurons receive prominent inputs from several regions, including the thalamus, hypothalamus, and olfactory cortex. Electrophysiological and histologic analysis demonstrates that oxytocin modulates inhibitory synaptic responses on MPOA-projection AHi neurons. In addition, AHi forms the excitatory monosynapse to MPOA, and pharmacological activation of MPOA-projection AHi neurons enhances only aggressive behavior, but not parental behavior. Interestingly, this promoted behavior was related to social experience in male mice. Collectively, our results identified a presynaptic partner of MPOA that can integrate sensory input and hormonal state, and trigger pup-directed aggression. The medial preoptic area (MPOA) plays critical roles in parental behavior, such as motor control, motivation, and social interaction. The MPOA projects to multiple brain regions, and these projections contribute to several neural controls in parental behavior. In contrast, how inputs to MPOA are regulated by social and environmental information is poorly understood. In this study, we focus on the amygdalohippocampal area (AHi) that connects to MPOA and expresses oxytocin receptor. We demonstrate the disruption of the expression of parental behavior triggered by the activation of MPOA-projection AHi neurons. This behavior may be regulated not only by oxytocin but also by neural input from several regions.
Topics: Aggression; Amygdala; Animals; Brain Mapping; Electrophysiological Phenomena; Hippocampus; Male; Mice; Mice, Inbred C57BL; Neural Inhibition; Neural Pathways; Neurons; Paternal Behavior; Preoptic Area; Receptors, Oxytocin; Social Behavior; Social Environment
PubMed: 32284340
DOI: 10.1523/JNEUROSCI.0438-19.2020 -
Neuron Oct 2021Deep brain temperature detection by hypothalamic warm-sensitive neurons (WSNs) has been proposed to provide feedback information relevant for thermoregulation. WSNs...
Deep brain temperature detection by hypothalamic warm-sensitive neurons (WSNs) has been proposed to provide feedback information relevant for thermoregulation. WSNs increase their action potential firing rates upon warming, a property that has been presumed to rely on the composition of thermosensitive ion channels within WSNs. Here, we describe a synaptic mechanism that regulates temperature sensitivity of preoptic WSNs and body temperature. Experimentally induced warming of the mouse hypothalamic preoptic area in vivo triggers body cooling. TRPM2 ion channels facilitate this homeostatic response and, at the cellular level, enhance temperature responses of WSNs, thereby linking WSN function with thermoregulation for the first time. Rather than acting within WSNs, we-unexpectedly-find TRPM2 to temperature-dependently increase synaptic drive onto WSNs by disinhibition. Our data emphasize a network-based interoceptive paradigm that likely plays a key role in encoding body temperature and that may facilitate integration of diverse inputs into thermoregulatory pathways.
Topics: Animals; Body Temperature; Body Temperature Regulation; Interoception; Mice; Mice, Knockout; Neural Inhibition; Neurons; Preoptic Area; Synapses; TRPM Cation Channels; Thermosensing
PubMed: 34672983
DOI: 10.1016/j.neuron.2021.10.001 -
Brain Structure & Function Jul 2018The lateral preoptic area (LPO) and ventral pallidum (VP) are structurally and functionally distinct territories in the subcommissural basal forebrain. It was recently...
The lateral preoptic area (LPO) and ventral pallidum (VP) are structurally and functionally distinct territories in the subcommissural basal forebrain. It was recently shown that unilateral infusion of the GABA receptor antagonist, bicuculline, into the LPO strongly invigorates exploratory locomotion, whereas bicuculline infused unilaterally into the VP has a negligible locomotor effect, but when infused bilaterally, produces vigorous, abnormal pivoting and gnawing movements and compulsive ingestion. This study was done to further characterize these responses. We observed that bilateral LPO infusions of bicuculline activate exploratory locomotion only slightly more potently than unilateral infusions and that unilateral and bilateral LPO injections of the GABA receptor agonist muscimol potently suppress basal locomotion, but only modestly inhibit locomotion invigorated by amphetamine. In contrast, unilateral infusions of muscimol into the VP affect basal and amphetamine-elicited locomotion negligibly, but bilateral VP muscimol infusions profoundly suppress both. Locomotor activation elicited from the LPO by bicuculline was inhibited modestly and profoundly by blockade of dopamine D2 and D1 receptors, respectively, but was not entirely abolished even under combined blockade of dopamine D1 and D2 receptors. That is, infusing the LPO with bic caused instances of near normal, even if sporadic, invigoration of locomotion in the presence of saturating dopamine receptor blockade, indicating that LPO can stimulate locomotion in the absence of dopamine signaling. Pivoting following bilateral VP bicuculline infusions was unaffected by dopamine D2 receptor blockade, but was completely suppressed by D1 receptor blockade. The present results are discussed in a context of neuroanatomical and functional organization underlying exploratory locomotion and adaptive movements.
Topics: Amphetamine; Animals; Basal Forebrain; Bicuculline; Central Nervous System Stimulants; Dopamine Agents; Functional Laterality; GABA-A Receptor Agonists; GABA-A Receptor Antagonists; Locomotion; Male; Movement; Muscimol; Preoptic Area; Rats; Rats, Sprague-Dawley; Time Factors
PubMed: 29700637
DOI: 10.1007/s00429-018-1669-2 -
Neuroscience Nov 2017The medial preoptic area (mPOA) participates in the temperature and cardiovascular control. The mPOA receives inputs from limbic structures and sends projections to...
The medial preoptic area (mPOA) participates in the temperature and cardiovascular control. The mPOA receives inputs from limbic structures and sends projections to hypothalamus and brainstem. Moreover, stress elicits pronounced neuronal activation in mPOA, suggesting its involvement in central neural pathway mediating stress responses. In the present study, we report the effect of acute mPOA neurotransmission inhibition using cobalt chloride (CoCl-nonselective synapse blocker) on the mean arterial pressure (MAP), heart rate (HR), body and tail temperature (T and T, respectively), as well as on the HR component of baroreflex. We also verified the participation of mPOA in the autonomic changes evoked by acute restraint stress (RS). Our results demonstrated that microinjection of CoCl into mPOA caused tachycardia, hyperthermia and a T decrease, without altering MAP. The inhibition of mPOA with CoCl increased the sympathetic component of cardiac baroreflex when assessed 10min after its administration. In addition, pretreatment of mPOA with CoCl increased RS-evoked tachycardic and hyperthermic responses evoked by RS when compared with aCSF-treated animals, without affecting the RS-evoked pressor response and the fall in T. In summary, our results suggest that mPOA exerts a tonic inhibitory influence on the sympathetic cardiac tone under both rest and stress conditions, modulating negatively the sympathetic component of baroreflex. Results also confirm the mPOA involvement in the control of body temperature because its inhibition was followed by a sustained increase in body temperature and vasoconstriction in the tail artery territory.
Topics: Animals; Autonomic Nervous System; Baroreflex; Blood Pressure; Body Temperature; Heart Rate; Male; Preoptic Area; Rats; Rats, Wistar; Rest; Restraint, Physical; Stress, Psychological
PubMed: 28943248
DOI: 10.1016/j.neuroscience.2017.09.026 -
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