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Biological Psychiatry Mar 2017The male bias in autism spectrum disorder incidence is among the most extreme of all neuropsychiatric disorders, yet the origins of the sex difference remain obscure.... (Review)
Review
The male bias in autism spectrum disorder incidence is among the most extreme of all neuropsychiatric disorders, yet the origins of the sex difference remain obscure. Developmentally, males are exposed to high levels of testosterone and its byproduct, estradiol. Together these steroids modify the course of brain development by altering neurogenesis, cell death, migration, differentiation, dendritic and axonal growth, synaptogenesis, and synaptic pruning, all of which can be deleteriously impacted during the course of developmental neuropsychiatric disorders. Elucidating the cellular mechanisms by which steroids modulate brain development provides valuable insights into how these processes may go awry. An emerging theme is the role of inflammatory signaling molecules and the innate immune system in directing brain masculinization, the evidence for which we review here. Evidence is also emerging that the neuroimmune system is overactivated in individuals with autism spectrum disorder. These combined observations lead us to propose that the natural process of brain masculinization puts males at risk by moving them closer to a vulnerability threshold that could more easily be breached by inflammation during critical periods of brain development. Two brain regions are highlighted: the preoptic area and the cerebellum. Both are developmentally regulated by the inflammatory prostaglandin E2, but in different ways. Microglia, innate immune cells of the brain, and astrocytes are also critical contributors to masculinization and illustrate the importance of nonneuronal cells to the health of the developing brain.
Topics: Animals; Astrocytes; Autism Spectrum Disorder; Behavior, Animal; Brain; Cerebellum; Dinoprostone; Disease Models, Animal; Female; Humans; Immunity, Innate; Inflammation; Male; Mice; Microglia; Neuroimmunomodulation; Preoptic Area; Rats; Risk Factors; Sex Characteristics; Sex Differentiation; Sex Factors
PubMed: 27871670
DOI: 10.1016/j.biopsych.2016.10.004 -
Brain Research May 2020Psychophysical stresses frequently increase sensitivity and response to pain, which is termed stress-induced hyperalgesia (SIH). However, the mechanism remains unknown....
Psychophysical stresses frequently increase sensitivity and response to pain, which is termed stress-induced hyperalgesia (SIH). However, the mechanism remains unknown. The subcortical areas such as medial preoptic area (MPO), dorsomedial nucleus of the hypothalamus (DMH), basolateral (BLA) and central nuclei of the amygdala (CeA), and the cortical areas such as insular (IC) and anterior cingulate cortices (ACC) play an important role in pain control via the descending pain modulatory system. In the present study we examined the expression of phosphorylated -cAMP-response element binding protein (pCREB) and the acetylation of histone H3 in these subcortical and cortical areas after repeated restraint stress to reveal changes in the subcortical and cortical areas that affect the function of descending pain modulatory system in the rats with SIH. The repeated restraint stress for 3 weeks induced a decrease in mechanical threshold in the rat hindpaw, an increase in the expression of pCREB in the MPO and an increase in the acetylation of histone H3 in the MPO, BLA and IC. The MPO was the only area that showed an increase in both the expression of pCREB and the acetylation of histone H3 among these examined areas after the repeated restraint stress. Furthermore, the number of pCREB-IR or acetylated histone H3-IR cells in the MPO was negatively correlated with the mechanical threshold. Together, our data represent the importance of the MPO among the subcortical and cortical areas that control descending pain modulatory system under the condition of SIH.
Topics: Acetylation; Animals; Brain; Cyclic AMP Response Element-Binding Protein; Histones; Hyperalgesia; Hypothalamus; Male; Pain; Pain Management; Pain Threshold; Phosphorylation; Preoptic Area; Rats; Rats, Sprague-Dawley; Restraint, Physical; Stress, Psychological
PubMed: 32135148
DOI: 10.1016/j.brainres.2020.146758 -
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 -
Behavioral Neuroscience Aug 2023The medial preoptic area (MPOA) is well known for its role in sexual and maternal behaviors. This region also plays an important role in affiliative social behaviors...
The medial preoptic area (MPOA) is well known for its role in sexual and maternal behaviors. This region also plays an important role in affiliative social behaviors outside reproductive contexts. We recently demonstrated that the MPOA is a central nucleus in which opioids govern highly rewarding social play behavior in adolescent rats. However, the neural circuit mechanisms underlying MPOA-mediated social play remain largely unresolved. We hypothesized that the MPOA unites a complementary neural system through which social play induces reward via a projection to the ventral tegmental area (VTA) and reduces a negative affective state through a projection to the periaqueductal gray (PAG). To test whether the two projection pathways are activated in response to social play behavior, we combined retrograde tract tracing with immediate early gene (IEG) expression and immunofluorescent labeling to identify opioid-sensitive projection pathways from the MPOA to VTA and PAG that are activated after performance of social play. Retrograde tracer, fluoro-gold (FG), was microinjected into the VTA or PAG. IEG expression (i.e., Egr1) was assessed and triple immunofluorescent labeling for mu opioid receptor (MOR), Egr1, and FG in the MPOA was performed after social play. We revealed that play animals displayed an increase in neurons double labeled for Egr1 + FG and triple labeled for MOR + Egr1 + FG in the MPOA projecting to both the VTA and PAG when compared to no-play rats. The increased activation of projection neurons that express MORs from MPOA to VTA or PAG after social play suggests that opioids may act through these projection pathways to govern social play. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
Topics: Female; Rats; Animals; Preoptic Area; Periaqueductal Gray; Neural Pathways; Ventral Tegmental Area; Analgesics, Opioid
PubMed: 36877484
DOI: 10.1037/bne0000555 -
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 -
ELife Mar 2021Maintaining stable body temperature through environmental thermal stressors requires detection of temperature changes, relay of information, and coordination of...
Maintaining stable body temperature through environmental thermal stressors requires detection of temperature changes, relay of information, and coordination of physiological and behavioral responses. Studies have implicated areas in the preoptic area of the hypothalamus (POA) and the parabrachial nucleus (PBN) as nodes in the thermosensory neural circuitry and indicate that the opioid system within the POA is vital in regulating body temperature. In the present study we identify neurons projecting to the POA from PBN expressing the opioid peptides dynorphin and enkephalin. Using mouse models, we determine that warm-activated PBN neuronal populations overlap with both prodynorphin (Pdyn) and proenkephalin (Penk) expressing PBN populations. Here we report that in the PBN () and () mRNA expressing neurons are partially overlapping subsets of a glutamatergic population expressing () (VGLUT2). Using optogenetic approaches we selectively activate projections in the POA from PBN Pdyn, Penk, and VGLUT2 expressing neurons. Our findings demonstrate that Pdyn, Penk, and VGLUT2 expressing PBN neurons are critical for physiological and behavioral heat defense.
Topics: Animals; Dynorphins; Enkephalins; Female; Hot Temperature; Male; Mice; Mice, Transgenic; Optogenetics; Parabrachial Nucleus; Preoptic Area; Protein Precursors
PubMed: 33667158
DOI: 10.7554/eLife.60779 -
The Journal of Neuroscience : the... Jan 2019AGRP (agouti-related neuropeptide) expressing inhibitory neurons sense caloric needs of an animal to coordinate homeostatic feeding. Recent evidence suggests that AGRP...
AGRP (agouti-related neuropeptide) expressing inhibitory neurons sense caloric needs of an animal to coordinate homeostatic feeding. Recent evidence suggests that AGRP neurons also suppress competing actions and motivations to mediate adaptive behavioral selection during starvation. Here, in adult mice of both sexes we show that AGRP neurons form inhibitory synapses onto ∼30% neurons in the medial preoptic area (mPOA), a region critical for maternal care. Remarkably, optogenetically stimulating AGRP neurons decreases maternal nest-building while minimally affecting pup retrieval, partly recapitulating suppression of maternal behaviors during food restriction. In parallel, optogenetically stimulating AGRP projections to the mPOA or to the paraventricular nucleus of hypothalamus but not to the LHA (lateral hypothalamus area) similarly decreases maternal nest-building. Chemogenetic inhibition of mPOA neurons that express Vgat (vesicular GABA transporter), the population targeted by AGRP terminals, also decreases maternal nest-building. In comparison, chemogenetic inhibition of neurons in the LHA that express vesicular glutamate transporter 2, another hypothalamic neuronal population critical for feeding and innate drives, is ineffective. Importantly, nest-building during low temperature thermal challenge is not affected by optogenetic stimulation of AGRP→mPOA projections. Finally, via optogenetic activation and inhibition we show that distinctive subsets of mPOA Vgat+ neurons likely underlie pup retrieval and maternal nest-building. Together, these results show that AGRP neurons can modulate maternal nest-building, in part through direct projections to the mPOA. This study corroborates other recent discoveries and underscores the broad functions that AGRP neurons play in antagonizing rivalry motivations to modulate behavioral outputs during hunger. In order for animals to initiate ethologically appropriate behaviors, they must typically decide between behavioral repertoires driven by multiple and often conflicting internal states. How neural pathways underlying individual behaviors interact to coherently modulate behavioral outputs, in particular to achieve a proper balance between behaviors that serve immediate individual needs versus those that benefit the propagation of the species, remains poorly understood. Here, by investigating projections from a neuronal population known to drive hunger behaviors to a brain region critical for maternal care, we show that activation of AGRP→mPOA projections in females dramatically inhibits maternal nest-building while leaving mostly intact pup retrieval behavior. Our findings shed new light on neural organization of behaviors and neural mechanisms that coordinate behavioral selection.
Topics: Agouti-Related Protein; Animals; Cold Temperature; Female; Food Deprivation; Hypothalamic Area, Lateral; Male; Maternal Behavior; Mice; Mice, Transgenic; Nerve Net; Nesting Behavior; Neurons; Optogenetics; Paraventricular Hypothalamic Nucleus; Preoptic Area; Vesicular Inhibitory Amino Acid Transport Proteins
PubMed: 30459220
DOI: 10.1523/JNEUROSCI.0958-18.2018 -
Neuroscience Letters Jul 2023The preoptic area and the hypothalamus are inextricably linked. Together, they represent an area of the forebrain that is essential for survival of the species....
The preoptic area and the hypothalamus are inextricably linked. Together, they represent an area of the forebrain that is essential for survival of the species. Observations in mammals have suggested a classification of these structures into four rostrocaudal areas and three mediolateral zones. Two species of crocodiles were investigated to determine if this scheme or a modification of it could be applied to these reptiles. The resulting classification identified three rostrocaudal areas based on their respective relationship to the ventricular system: preoptic, anterior, and tuberal and four mediolateral zones: ependyma, periventricular, medial, and lateral. This scheme avoided the cumbersome and complicated nomenclature that has traditionally been used for morphologic studies of these areas in other reptiles, including crocodiles. The present classification is simple, straightforward, and readily applicable to other reptiles.
Topics: Animals; Hypothalamus; Preoptic Area; Reptiles; Mammals
PubMed: 37394133
DOI: 10.1016/j.neulet.2023.137368