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Science (New York, N.Y.) Oct 2023During pregnancy, physiological adaptations prepare the female body for the challenges of motherhood. Becoming a parent also requires behavioral adaptations. Such...
During pregnancy, physiological adaptations prepare the female body for the challenges of motherhood. Becoming a parent also requires behavioral adaptations. Such adaptations can occur as early as during pregnancy, but how pregnancy hormones remodel parenting circuits to instruct preparatory behavioral changes remains unknown. We found that action of estradiol and progesterone on galanin (Gal)-expressing neurons in the mouse medial preoptic area (MPOA) is critical for pregnancy-induced parental behavior. Whereas estradiol silences MPOA neurons and paradoxically increases their excitability, progesterone permanently rewires this circuit node by promoting dendritic spine formation and recruitment of excitatory synaptic inputs. This MPOA-specific neural remodeling sparsens population activity in vivo and results in persistently stronger, more selective responses to pup stimuli. Pregnancy hormones thus remodel parenting circuits in anticipation of future behavioral need.
Topics: Animals; Female; Mice; Pregnancy; Estradiol; Maternal Behavior; Parenting; Preoptic Area; Progesterone; Models, Animal; Neurons
PubMed: 37797007
DOI: 10.1126/science.adi0576 -
Nature Communications Aug 2023A comorbidity of chronic pain is sleep disturbance. Here, we identify a dual-functional ensemble that regulates both pain-like behaviour induced by chronic constrictive...
A comorbidity of chronic pain is sleep disturbance. Here, we identify a dual-functional ensemble that regulates both pain-like behaviour induced by chronic constrictive injury or complete Freund's adjuvant, and sleep wakefulness, in the nucleus accumbens (NAc) in mice. Specifically, a select population of NAc neurons exhibits increased activity either upon nociceptive stimulation or during wakefulness. Experimental activation of the ensemble neurons exacerbates pain-like (nociceptive) responses and reduces NREM sleep, while inactivation of these neurons produces the opposite effects. Furthermore, NAc ensemble primarily consists of D1 neurons and projects divergently to the ventral tegmental area (VTA) and preoptic area (POA). Silencing an ensemble innervating VTA neurons selectively increases nociceptive responses without affecting sleep, whereas inhibiting ensemble-innervating POA neurons decreases NREM sleep without affecting nociception. These results suggest a common NAc ensemble that encodes chronic pain and controls sleep, and achieves the modality specificity through its divergent downstream circuit targets.
Topics: Mice; Animals; Nucleus Accumbens; Chronic Pain; Ventral Tegmental Area; Neurons; Sleep
PubMed: 37543693
DOI: 10.1038/s41467-023-40450-3 -
Nature Communications Aug 2023Thermal homeostasis is vital for mammals and is controlled by brain neurocircuits. Yet, the neural pathways responsible for cold defense regulation are still unclear....
Thermal homeostasis is vital for mammals and is controlled by brain neurocircuits. Yet, the neural pathways responsible for cold defense regulation are still unclear. Here, we found that a pathway from the lateral parabrachial nucleus (LPB) to the dorsomedial hypothalamus (DMH), which runs parallel to the canonical LPB to preoptic area (POA) pathway, is also crucial for cold defense. Together, these pathways make an equivalent and cumulative contribution, forming a parallel circuit. Specifically, activation of the LPB → DMH pathway induced strong cold-defense responses, including increases in thermogenesis of brown adipose tissue (BAT), muscle shivering, heart rate, and locomotion. Further, we identified somatostatin neurons in the LPB that target DMH to promote BAT thermogenesis. Therefore, we reveal a parallel circuit governing cold defense in mice, which enables resilience to hypothermia and provides a scalable and robust network in heat production, reshaping our understanding of neural circuit regulation of homeostatic behaviors.
Topics: Mice; Animals; Thermogenesis; Preoptic Area; Neural Pathways; Homeostasis; Hypothermia; Adipose Tissue, Brown; Cold Temperature; Mammals
PubMed: 37582782
DOI: 10.1038/s41467-023-40504-6 -
Nature Neuroscience Sep 2023Fluctuations in reproductive hormone levels are associated with mood disruptions in women, such as in postpartum and perimenopausal depression. However, the neural...
Fluctuations in reproductive hormone levels are associated with mood disruptions in women, such as in postpartum and perimenopausal depression. However, the neural circuit mechanisms remain unclear. Here we report that medial preoptic area (MPOA) GABAergic neurons mediate multifaceted depressive-like behaviors in female mice after ovarian hormone withdrawal (HW), which can be attributed to downregulation of activity in Esr1 (estrogen receptor-1)-expressing GABAergic neurons. Enhancing activity of these neurons ameliorates depressive-like behaviors in HW-treated mice, whereas reducing their activity results in expression of these behaviors. Two separate subpopulations mediate different symptoms: a subpopulation projecting to the ventral tegmental area (VTA) mediates anhedonia and another projecting to the periaqueductal gray mediates immobility. These projections enhance activity of dopaminergic neurons in the VTA and serotonergic neurons in the dorsal raphe, respectively, with increased release of dopamine and serotonin, possibly through disinhibition mechanisms. Thus, the MPOA is a hub that mediates depressive-like behaviors resulting from transitions in reproductive hormone levels.
Topics: Mice; Female; Animals; Preoptic Area; Ventral Tegmental Area; Dopaminergic Neurons; GABAergic Neurons
PubMed: 37524978
DOI: 10.1038/s41593-023-01397-2 -
Pharmacology & Therapeutics Sep 2023Benzodiazepine, a classical medication utilized in the treatment of insomnia, operates by augmenting the activity of the GABA receptor. This underscores the significance... (Review)
Review
Benzodiazepine, a classical medication utilized in the treatment of insomnia, operates by augmenting the activity of the GABA receptor. This underscores the significance of GABAergic neurotransmission in both the initiation and maintenance of sleep. Nevertheless, an increasing body of evidence substantiates the notion that GABA-mediated neurotransmission also assumes a vital role in promoting wakefulness in specific neuronal circuits. Despite the longstanding belief in the pivotal function of GABA in regulating the sleep-wake cycle, there exists a dearth of comprehensive documentation regarding the specific regions within the central nervous system where GABAergic neurons are crucial for these functions. In this review, we delve into the involvement of GABAergic neurons in the regulation of sleep-wake cycles, with particular focus on those located in the preoptic area (POA) and ventral tegmental area (VTA). Recent research, including our own, has further underscored the importance of GABAergic neurotransmission in these areas for the regulation of sleep-wake cycles.
Topics: Humans; Sleep; Wakefulness; GABAergic Neurons; Central Nervous System; Receptors, GABA-A; gamma-Aminobutyric Acid
PubMed: 37541595
DOI: 10.1016/j.pharmthera.2023.108505 -
Sleep & Breathing = Schlaf & Atmung Dec 2023The purpose of this study is to examine the pathophysiology underlying sleep apnea (SA). (Review)
Review
OBJECTIVE
The purpose of this study is to examine the pathophysiology underlying sleep apnea (SA).
BACKGROUND
We consider several critical features of SA including the roles played by the ascending reticular activating system (ARAS) that controls vegetative functions and electroencephalographic findings associated with both SA and normal sleep. We evaluate this knowledge together with our current understanding of the anatomy, histology, and physiology of the mesencephalic trigeminal nucleus (MTN) and mechanisms that contribute directly to normal and disordered sleep. MTN neurons express γ-aminobutyric acid (GABA) receptors which activate them (make chlorine come out of the cells) and that can be activated by GABA released from the hypothalamic preoptic area.
METHOD
We reviewed the published literature focused on sleep apnea (SA) reported in Google Scholar, Scopus, and PubMed databases.
RESULTS
The MTN neurons respond to the hypothalamic GABA release by releasing glutamate that activates neurons in the ARAS. Based on these findings, we conclude that a dysfunctional MTN may be incapable of activating neurons in the ARAS, notably those in the parabrachial nucleus, and that this will ultimately lead to SA. Despite its name, obstructive sleep apnea (OSA) is not caused by an airway obstruction that prevents breathing.
CONCLUSIONS
While obstruction may contribute to the overall pathology, the primary factor involved in this scenario is the lack of neurotransmitters.
Topics: Humans; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Respiration; Sleep; gamma-Aminobutyric Acid
PubMed: 36976413
DOI: 10.1007/s11325-023-02783-7 -
Frontiers in Behavioral Neuroscience 2023The postpartum period is a demanding time during which mothers experience numerous physiological adaptations that enable them to care for their offspring while... (Review)
Review
The postpartum period is a demanding time during which mothers experience numerous physiological adaptations that enable them to care for their offspring while maintaining their wellbeing. Hypocretins, also known as orexins, are neuropeptides synthesized by hypothalamic neurons that play a fundamental role in several functions, including the promotion of wakefulness and motivated behaviors, such as maternal care. In this regard, several findings suggest that the activity of the hypocretinergic system increases in the early postpartum period and begins to decline as weaning approaches. In particular, hypocretins within the medial preoptic area, a crucial region during this period, modulate both maternal behavior and sleep. Although further studies are necessary to obtain a comprehensive understanding of the role of hypocretins in lactating females, current research suggests that this system participates in promoting active components of maternal behavior and regulating wakefulness and sleep adjustments during the postpartum period, potentially leading to increased wakefulness during this stage. These adaptive adjustments enable the mother to cope with the continuously changing demands of the pups.
PubMed: 37456808
DOI: 10.3389/fnbeh.2023.1184885 -
Current Biology : CB Dec 2023Endotherms can survive low temperatures and food shortage by actively entering a hypometabolic state known as torpor. Although the decrease in metabolic rate and body...
Endotherms can survive low temperatures and food shortage by actively entering a hypometabolic state known as torpor. Although the decrease in metabolic rate and body temperature (Tb) during torpor is controlled by the brain, the specific neural circuits underlying these processes have not been comprehensively elucidated. In this study, we identify the neural circuits involved in torpor regulation by combining whole-brain mapping of torpor-activated neurons, cell-type-specific manipulation of neural activity, and viral tracing-based circuit mapping. We find that Trpm2-positive neurons in the preoptic area and Vgat-positive neurons in the dorsal medial hypothalamus are activated during torpor. Genetic silencing shows that the activity of either cell type is necessary to enter the torpor state. Finally, we show that these cells receive projections from the arcuate and suprachiasmatic nucleus and send projections to brain regions involved in thermoregulation. Our results demonstrate an essential role of hypothalamic neurons in the regulation of Tb and metabolic rate during torpor and identify critical nodes of the torpor regulatory network.
Topics: Hypothalamus; Torpor; Preoptic Area; Suprachiasmatic Nucleus; Brain
PubMed: 37992720
DOI: 10.1016/j.cub.2023.10.076