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Neurochemical Research Oct 2019The behavior of female rats changes profoundly as they become mothers. The brain region that plays a central role in this regulation is the preoptic area, and lesions in...
The behavior of female rats changes profoundly as they become mothers. The brain region that plays a central role in this regulation is the preoptic area, and lesions in this area eliminates maternal behaviors in rodents. The molecular background of the behavioral changes has not been established yet; therefore, in the present study, we applied proteomics to compare protein level changes associated with maternal care in the rat preoptic area. Using 2-dimensional fluorescence gel electrophoresis followed by identification of altered spots with mass spectrometry, 12 proteins were found to be significantly increased, and 6 proteins showed a significantly reduced level in mothers. These results show some similarities with a previous proteomics study of the maternal medial prefrontal cortex and genomics approaches applied to the preoptic area. Gene ontological analysis suggested that most altered proteins are involved in glucose metabolism and neuroplasticity. These proteins may support the maintenance of increased neuronal activity in the preoptic area, and morphological changes in preoptic neuronal circuits are known to take place in mothers. An increase in the level of alpha-crystallin B chain (Cryab) was confirmed by Western blotting. This small heat shock protein may also contribute to maintaining the increased activity of preoptic neurons by stabilizing protein structures. Common regulator and target analysis of the altered proteins suggested a role of prolactin in the molecular changes in the preoptic area. These results first identified the protein level changes in the maternal preoptic area. The altered proteins contribute to the maintenance of maternal behaviors and may also be relevant to postpartum depression, which can occur as a molecular level maladaptation to motherhood.
Topics: Animals; Behavior, Animal; Electrophoresis, Gel, Two-Dimensional; Female; Maternal Behavior; Neurons; Prefrontal Cortex; Preoptic Area; Proteomics; Rats
PubMed: 30847857
DOI: 10.1007/s11064-019-02755-y -
Cell Metabolism Jul 2021The preoptic area (POA) is a key brain region for regulation of body temperature (Tb), dictating thermogenic, cardiovascular, and behavioral responses that control Tb....
The preoptic area (POA) is a key brain region for regulation of body temperature (Tb), dictating thermogenic, cardiovascular, and behavioral responses that control Tb. Previously characterized POA neuronal populations all reduced Tb when activated. Using mice, we now identify POA neurons expressing bombesin-like receptor 3 (POA) as a population whose activation increased Tb; inversely, acute inhibition of these neurons reduced Tb. POA neurons that project to either the paraventricular nucleus of the hypothalamus or the dorsomedial hypothalamus increased Tb, heart rate, and blood pressure via the sympathetic nervous system. Long-term inactivation of POA neurons caused increased Tb variability, overshooting both increases and decreases in Tb set point, with RNA expression profiles suggesting multiple types of POA neurons. Thus, POA neuronal populations regulate Tb and heart rate, contribute to cold defense, and fine-tune feedback control of Tb. These findings advance understanding of homeothermy, a defining feature of mammalian biology.
Topics: Animals; Body Temperature; Body Temperature Regulation; Heart Rate; Male; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Transgenic; Neurons; Preoptic Area; Receptors, Bombesin; Signal Transduction; Sympathetic Nervous System; Thermogenesis
PubMed: 34038711
DOI: 10.1016/j.cmet.2021.05.001 -
Scientific Reports Oct 2020Within the central neural circuitry for thermoregulation, the balance between excitatory and inhibitory inputs to the dorsomedial hypothalamus (DMH) determines the level...
Within the central neural circuitry for thermoregulation, the balance between excitatory and inhibitory inputs to the dorsomedial hypothalamus (DMH) determines the level of activation of brown adipose tissue (BAT) thermogenesis. We employed neuroanatomical and in vivo electrophysiological techniques to identify a source of excitation to thermogenesis-promoting neurons in the DMH that is required for cold defense and fever. Inhibition of median preoptic area (MnPO) neurons blocked the BAT thermogenic responses during both PGE-induced fever and cold exposure. Disinhibition or direct activation of MnPO neurons induced a BAT thermogenic response in warm rats. Blockade of ionotropic glutamate receptors in the DMH, or brain transection rostral to DMH, blocked cold-evoked or NMDA in MnPO-evoked BAT thermogenesis. RNAscope technique identified a glutamatergic population of MnPO neurons that projects to the DMH and expresses c-Fos following cold exposure. These discoveries relative to the glutamatergic drive to BAT sympathoexcitatory neurons in DMH augment our understanding of the central thermoregulatory circuitry in non-torpid mammals. Our data will contribute to the development of novel therapeutic approaches to induce therapeutic hypothermia for treating drug-resistant fever, and for improving glucose and energy homeostasis.
Topics: Adipose Tissue, Brown; Animals; Body Temperature Regulation; Cold Temperature; Dorsomedial Hypothalamic Nucleus; Fever; Male; Neurons; Preoptic Area; Rats; Rats, Wistar; Sympathetic Nervous System; Thermogenesis
PubMed: 33093475
DOI: 10.1038/s41598-020-74272-w -
The Journal of Neuroscience : the... Sep 2000Penile erections are a characteristic phenomenon of paradoxical sleep (PS), or rapid eye movement sleep. Although the neural mechanisms of PS-related erections are...
Penile erections are a characteristic phenomenon of paradoxical sleep (PS), or rapid eye movement sleep. Although the neural mechanisms of PS-related erections are unknown, the forebrain likely plays a critical role (Schmidt et al., 1999). The preoptic area is implicated in both sleep generation and copulatory mechanisms, suggesting it may be a primary candidate in PS erectile control. Continuous recordings of penile erections, body temperature, and sleep-wake states were performed before and up to 3 weeks after ibotenic acid lesions of the preoptic forebrain in three groups of rats. Neurotoxic lesions involving the medial preoptic area (MPOA) and anterior hypothalamus (n = 5) had no significant effects on either erectile activity or sleep-wake architecture. In contrast, bilateral lesions of the lateral preoptic region, with (n = 4) or without (n = 5) MPOA involvement, resulted in a significant decrease in the number of erections per hour of PS, number of PS-related erections, and PS phases exhibiting an erection. Lesion analysis revealed that the candidate structures for PS erectile control include both the lateral preoptic area (LPOA) and ventral division of the bed nucleus of the stria terminalis; however, lesions of the LPOA were the most effective in disrupting PS erectile activity. LPOA lesioning also resulted in a long-lasting insomnia, characterized by the significant increase in wakefulness and decrease in slow wave sleep (SWS). PS architecture and waking-state erections remained unchanged after lesion in all groups. These data identify an essential role of the LPOA in both PS-related erectile mechanisms and SWS generation. Moreover, higher erectile mechanisms appear to be context-specific because LPOA lesioning selectively disrupted PS-related erections while leaving waking-state erections intact.
Topics: Animals; Body Temperature; Brain Mapping; Ibotenic Acid; Male; Neurons; Penile Erection; Preoptic Area; Rats; Rats, Sprague-Dawley; Septal Nuclei; Sleep; Sleep, REM; Wakefulness
PubMed: 10964969
DOI: 10.1523/JNEUROSCI.20-17-06640.2000 -
Folia Histochemica Et Cytobiologica 2011This study provides a detailed description of cocaine-and amphetamine-regulated transcript (CART) distribution and the co-localization pattern of CART and gonadotropin...
This study provides a detailed description of cocaine-and amphetamine-regulated transcript (CART) distribution and the co-localization pattern of CART and gonadotropin releasing hormone (GnRH), somatostatin (SOM), neuropeptide Y (NPY), cholecystokinin (CCK), and substance P (SP) in the preoptic area (POA) of the domestic pig. The POA displays a low density of immunoreactive cells and rich immunoreactivity for CART in fibers. CART-immunoreactive (CART-IR) cell bodies were single and faintly stained, and located in the medial preoptic area (MPA) and the periventricular region of the POA. A high density of immunoreactive fibers was observed in the periventricular preoptic nucleus (PPN); a high to moderate density of fibers was observed in the MPA; but in the dorso-medial region of the MPA the highest density of fibers in the whole POA was observed. The lateral preoptic area (LPA) exhibited a less dense concentration of CART-immunoreactive fibers than the MPA. The median preoptic nucleus (MPN) showed moderate to low expression of staining fibers. In the present study, dual-labeling immunohistochemistry was used to show that CART-IR cell bodies do not contain any GnRH and SP. CART-positive fibers were identified in close apposition with GnRH neurons. This suggests that CART may influence GnRH secretion. Double staining revealed that CART-IR structures do not co-express any of the substances we studied, but a very small population of CART-IR fibers also contain SOM, CCK or SP.
Topics: Amphetamine; Animals; Cholecystokinin; Cocaine; Gonadotropin-Releasing Hormone; Immunohistochemistry; Nerve Tissue Proteins; Neurons; Neuropeptide Y; Preoptic Area; Somatostatin; Substance P; Sus scrofa
PubMed: 22252754
DOI: 10.5603/fhc.2011.0083 -
Current Biology : CB May 2022Previous studies suggest that the median preoptic nucleus (MnPO) of the hypothalamus plays an important role in regulating the wake-sleep cycle and, in particular,...
Previous studies suggest that the median preoptic nucleus (MnPO) of the hypothalamus plays an important role in regulating the wake-sleep cycle and, in particular, homeostatic sleep drive. However, the precise cellular phenotypes, targets, and central mechanisms by which the MnPO neurons regulate the wake-sleep cycle remain unknown. Both excitatory and inhibitory MnPO neurons innervate brain regions implicated in sleep promotion and maintenance, suggesting that both cell types may participate in sleep control. Using genetically targeted approaches, we investigated the role of the MnPO GABAergic (MnPO) and glutamatergic (MnPO) neurons in modulating wake-sleep behavior of mice. We found that both neuron populations differentially participate in wake-sleep control, with MnPO neurons being involved in sleep homeostasis and MnPO neurons facilitating sleep during allostatic (stressful) challenges.
Topics: Animals; Glutamic Acid; Mice; Neurons; Preoptic Area; Sleep; gamma-Aminobutyric Acid
PubMed: 35385692
DOI: 10.1016/j.cub.2022.03.039 -
Nature May 2017In humans and other mammalian species, lesions in the preoptic area of the hypothalamus cause profound sleep impairment, indicating a crucial role of the preoptic area...
In humans and other mammalian species, lesions in the preoptic area of the hypothalamus cause profound sleep impairment, indicating a crucial role of the preoptic area in sleep generation. However, the underlying circuit mechanism remains poorly understood. Electrophysiological recordings and c-Fos immunohistochemistry have shown the existence of sleep-active neurons in the preoptic area, especially in the ventrolateral preoptic area and median preoptic nucleus. Pharmacogenetic activation of c-Fos-labelled sleep-active neurons has been shown to induce sleep. However, the sleep-active neurons are spatially intermingled with wake-active neurons, making it difficult to target the sleep neurons specifically for circuit analysis. Here we identify a population of preoptic area sleep neurons on the basis of their projection target and discover their molecular markers. Using a lentivirus expressing channelrhodopsin-2 or a light-activated chloride channel for retrograde labelling, bidirectional optogenetic manipulation, and optrode recording, we show that the preoptic area GABAergic neurons projecting to the tuberomammillary nucleus are both sleep active and sleep promoting. Furthermore, translating ribosome affinity purification and single-cell RNA sequencing identify candidate markers for these neurons, and optogenetic and pharmacogenetic manipulations demonstrate that several peptide markers (cholecystokinin, corticotropin-releasing hormone, and tachykinin 1) label sleep-promoting neurons. Together, these findings provide easy genetic access to sleep-promoting preoptic area neurons and a valuable entry point for dissecting the sleep control circuit.
Topics: Animals; Biomarkers; Channelrhodopsins; Chloride Channels; Cholecystokinin; Corticotropin-Releasing Hormone; Female; GABAergic Neurons; Hypothalamic Area, Lateral; Male; Mice; Neuroanatomical Tract-Tracing Techniques; Neurons; Optogenetics; Preoptic Area; Proto-Oncogene Proteins c-fos; Ribosomes; Sequence Analysis, RNA; Single-Cell Analysis; Sleep; Tachykinins; Transcriptome; Wakefulness
PubMed: 28514446
DOI: 10.1038/nature22350 -
The Journal of Neuroscience : the... Nov 2023The medial preoptic area (MPOA) is a sexually dimorphic region of the brain that regulates social behaviors. The sexually dimorphic nucleus (SDN) of the MPOA has been...
Two-Step Actions of Testicular Androgens in the Organization of a Male-Specific Neural Pathway from the Medial Preoptic Area to the Ventral Tegmental Area for Modulating Sexually Motivated Behavior.
The medial preoptic area (MPOA) is a sexually dimorphic region of the brain that regulates social behaviors. The sexually dimorphic nucleus (SDN) of the MPOA has been studied to understand sexual dimorphism, although the anatomy and physiology of the SDN is not fully understood. Here, we characterized SDN neurons that contribute to sexual dimorphism and investigated the mechanisms underlying the emergence of such neurons and their roles in social behaviors. A target-specific neuroanatomical study using transgenic mice expressing Cre recombinase under the control of , a gene expressed abundantly in the SDN, revealed that SDN neurons are divided into two subpopulations, GABA neurons projecting to the ventral tegmental area (VTA), where they link to the dopamine system (Calb neurons), and GABA neurons that extend axons in the MPOA or project to neighboring regions (Calb neurons). Calb neurons were abundant in males, but were scarce or absent in females. There was no difference in the number of Calb neurons between sexes. Additionally, we found that emergence of Calb neurons requires two testicular androgen actions that occur first in the postnatal period and second in the peripubertal period. Chemogenetic analyses of Calb neurons indicated a role in modulating sexual motivation in males. Knockdown of in the MPOA reduced the intromission required for males to complete copulation. These findings provide strong evidence that a male-specific neural pathway from the MPOA to the VTA is organized by the two-step actions of testicular androgens for the modulation of sexually motivated behavior. The MPOA is a sexually dimorphic region of the brain that regulates social behaviors, although its sexual dimorphism is not fully understood. Here, we describe a population of MPOA neurons that contribute to the sexual dimorphism. These neurons only exist in masculinized brains, and they project their axons to the ventral tegmental area, where they link to the dopamine system. Emergence of such neurons requires two testicular androgen actions that occur first in the postnatal period and second in the peripubertal period. These MPOA neurons endow masculinized brains with a neural pathway from the MPOA to the ventral tegmental area and modulate sexually motivated behavior in males.
Topics: Animals; Mice; Female; Male; Preoptic Area; Androgens; Ventral Tegmental Area; Dopamine; Neural Pathways; Mice, Transgenic
PubMed: 37722849
DOI: 10.1523/JNEUROSCI.0361-23.2023 -
Brain Structure & Function Dec 2019The median preoptic nucleus (MnPO) and the ventrolateral preoptic nucleus (VLPO) are two brain structures that contain neurons essential for promoting non-rapid eye...
The median preoptic nucleus (MnPO) and the ventrolateral preoptic nucleus (VLPO) are two brain structures that contain neurons essential for promoting non-rapid eye movement (NREM) sleep. However, their connections are still largely unknown. Here, we describe for the first time a slice preparation with an oblique coronal slicing angle at 70° from the horizontal in which their connectivity is preserved. Using the in vivo iDISCO method following viral infection of the MnPO or ex vivo biocytin crystal deposition in the MnPO of mouse brain slices, we revealed a strong axonal pathway from the MnPO to the VLPO. Then, to further explore the functionality of these projections, acute 70° slices were placed on multielectrode arrays (MEAs) and electrical stimulations were performed near the MnPO. Recordings of the signals propagation throughout the slices revealed a preferential pathway from the MnPO to the VLPO. Finally, we performed an input-output curve of field responses evoked by stimulation of the MnPO and recorded in the VLPO. We found that field responses were inhibited by GABA receptor antagonist, suggesting that afferent inputs from the MnPO activate VLPO neuronal networks by disinhibition.
Topics: Animals; Axons; Male; Mice, Inbred C57BL; Neural Pathways; Neuroanatomical Tract-Tracing Techniques; Neurons; Preoptic Area
PubMed: 31493023
DOI: 10.1007/s00429-019-01935-4 -
Neuron Apr 2018In this issue of Neuron, Fang et al. (2018) identified a neural circuit that connects the medial preoptic area to the ventral tegmental area as a critical pathway for...
In this issue of Neuron, Fang et al. (2018) identified a neural circuit that connects the medial preoptic area to the ventral tegmental area as a critical pathway for pup retrieval in female mice.
Topics: Animals; Female; Humans; Maternal Behavior; Mice; Neurons; Preoptic Area; Ventral Tegmental Area
PubMed: 29621491
DOI: 10.1016/j.neuron.2018.03.025