Edinger-Westphal peptidergic neurons enable maternal preparatory nesting

Neuron, Journal Year: 2022, Volume and Issue: 110(8), P. 1385 - 1399.e8

Published: Feb. 4, 2022

Optimizing reproductive fitness in mammalians requires behavioral adaptations during pregnancy. Maternal preparatory nesting is an essential behavior for the survival of upcoming litter. Brain-wide immediate early gene mapping mice evoked by sequences revealed that phases nest construction strongly activate peptidergic neurons Edinger-Westphal nucleus pregnant mice. Genetic ablation, bidirectional neuromodulation, and vitro vivo activity recordings demonstrated these are to modulate arousal before sleep promote specifically. We show enable effects progesterone on modulating a broad network downstream targets. Our study deciphers role midbrain CART+ pregnancy vital fitness.

Language: Английский

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Priorities for research on neuromodulatory subcortical systems in Alzheimer's disease: Position paper from the NSS PIA of ISTAART

Alzheimer s & Dementia, Journal Year: 2023, Volume and Issue: 19(5), P. 2182 - 2196

Published: Jan. 15, 2023

Abstract The neuromodulatory subcortical system (NSS) nuclei are critical hubs for survival, hedonic tone, and homeostasis. Tau‐associated NSS degeneration occurs early in Alzheimer's disease (AD) pathogenesis, long before the emergence of pathognomonic memory dysfunction cortical lesions. Accumulating evidence supports role behavioral neuropsychiatric manifestations featured AD. Experimental studies even suggest that AD‐associated drives brain neuroinflammatory status contributes to progression, including exacerbation Given important pathophysiologic etiologic roles involve AD stages, there is an urgent need expand our understanding mechanisms underlying vulnerability more precisely detail clinical progression changes Here, Professional Interest Area International Society Advance Research Treatment highlights knowledge gaps about within provides recommendations priorities specific research, biomarker development, modeling, intervention. Highlights Neuromodulatory degenerate pathological stages. pathophysiology exacerbated by degeneration. symptoms dementia. Biomarkers integrity would be value‐creating dementia care. present strategic prospects disease‐modifying therapies.

Language: Английский

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Midbrain ghrelin receptor signalling regulates binge drinking in a sex specific manner

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 15, 2025

Abstract Risky drinking rates are rising, particularly in women, yet sex as a biological variable has only recently gained traction. The centrally projecting Edinger-Westphal (EWcp) nucleus emerged key regulator of alcohol consumption. Here we found that EWcp peptidergic cells reduce binge specifically female mice. We show this effect is mediated by the ghrelin receptor (GHSR), with inhibition blocking ghrelin-induced and Ghsr knockdown , but not glutamatergic or ventral tegmental area cells, reducing females, independent circulating hormones. Female mice showed higher expression, neurons were more sensitive to ghrelin. Moreover, intra-EWcp delivery GHSR inverse agonist antagonist reduced drinking, suggesting direct actions These findings highlight critical mediator excessive consumption via mice, offering insights into system’s role

Language: Английский

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A Sleep‐Specific Midbrain Target for Sevoflurane Anesthesia

Advanced Science, Journal Year: 2023, Volume and Issue: 10(15)

Published: March 24, 2023

Sevoflurane has been the most widely used inhaled anesthetics with a favorable recovery profile; however, precise mechanisms underlying its anesthetic action are still not completely understood. Here authors show that sevoflurane activates cluster of urocortin 1 (UCN1

Language: Английский

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Cholecystokinin neurotransmission in the central nervous system: Insights into its role in health and disease

BioFactors, Journal Year: 2024, Volume and Issue: unknown

Published: May 22, 2024

Abstract Cholecystokinin (CCK) plays a key role in various brain functions, including both health and disease states. Despite the extensive research conducted on CCK, there remain several important questions regarding its specific brain. As result, existing body of literature subject is complex sometimes conflicting. The primary objective this review article to provide comprehensive overview recent advancements understanding central nervous system with emphasis elucidating CCK's mechanisms for neuroplasticity, exploring interactions other neurotransmitters, discussing significant involvement neurological disorders. Studies demonstrate that CCK mediates inhibitory long‐term potentiation (iLTP) excitatory (eLTP) Activation GPR173 receptor could facilitate iLTP, while B (CCKBR) facilitates eLTP. receptors' expression different neurons regulates activity, neurotransmitter release, plasticity, emphasizing modulating function. Furthermore, pivotal emotional states, Alzheimer's disease, addiction, schizophrenia, epileptic conditions. Targeting cell types circuits holds promise as therapeutic strategy alleviating these

Language: Английский

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Mu Opioid Receptor–Expressing Neurons in the Dorsal Raphe Nucleus Are Involved in Reward Processing and Affective Behaviors

Biological Psychiatry, Journal Year: 2023, Volume and Issue: 94(11), P. 842 - 851

Published: June 5, 2023

Language: Английский

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Neural circuit mechanisms of the cholecystokinin (CCK) neuropeptide system in addiction

Addiction Neuroscience, Journal Year: 2022, Volume and Issue: 3, P. 100024 - 100024

Published: June 17, 2022

Given historical focus on the roles for cholecystokinin (CCK) as a peripheral hormone controlling gastrointestinal processes and brainstem peptide regulating food intake, study of CCK limbic neuromodulator coordinating reward-seeking emotional behavior remains underappreciated. Furthermore, localization to specialized interneurons throughout hippocampus cortex relegated being examined primarily static cell type marker rather than dynamic functional neuromodulator. Yet, over three decades literature have been generated by efforts delineate central mechanisms addiction-related behaviors mediated system across striatum, amygdala, hypothalamus, midbrain. Here, we cover fundamental findings that implicate neuron activity receptor signaling in modulating drug intake drug-seeking (focusing psychostimulants, opioids, alcohol). In doing so, highlight few studies indicate sex differences expression corresponding effects, emphasizing importance examining hormonal influences biological variable translating basic science discoveries effective treatments substance use disorders human patients. Finally, point toward understudied subcortical sources endogenous describe how continued neurotechnology advancements can be leveraged modernize understanding neural circuit underlying release addiction-relevant behaviors.

Language: Английский

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SH2B1 Defends Against Energy Imbalance, Obesity, and Metabolic Disease via a Paraventricular Hypothalamus→Dorsal Raphe Nucleus Neurocircuit

Advanced Science, Journal Year: 2024, Volume and Issue: 11(31)

Published: June 17, 2024

Abstract SH2B1 mutations are associated with obesity, type 2 diabetes, and metabolic dysfunction‐associated steatotic liver disease (MASLD) in humans. Global deletion of Sh2b1 results severe MASLD mice. Neuron‐specific restoration rescues the obesity phenotype Sh2b1‐null mice, indicating that brain is a main target. However, neurocircuits remain elusive. SH2B1‐expressing neurons paraventricular hypothalamus (PVH ) PVH →dorsal raphe nucleus (DRN) neurocircuit identified here. axons monosynaptically innervate DRN neurons. Optogenetic stimulation axonal fibers suppresses food intake. Chronic inhibition causes obesity. In male female either embryonic‐onset or adult‐onset energy imbalance, insulin resistance, glucose intolerance, MASLD. Ablation DRN‐projecting subpopulation also disorders. Conversely, overexpression total protects against diet‐induced binds to TrkB enhances brain‐derived neurotrophic factor (BDNF) signaling. induces BDNF resistance PVH, contributing conclusion, these unveil previously unrecognized →DRN through which defends by enhancing BDNF/TrkB

Language: Английский

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Edinger-Westphal ghrelin receptor signalling regulates binge alcohol consumption in a sex specific manner

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 27, 2024

Abstract Background Rates of risky drinking are continuing to rise, particularly in women, yet sex as a biological variable has been largely ignored. An emerging understudied potential component this circuitry is the central projecting Edinger-Westphal (EWcp), which made up two prominent, but distinct cell populations expressing either an array neuropeptides (including cocaine and amphetamine regulated transcript; CART) or vGlut2 (glutamatergic). Methods Here, we use combination approaches including genetic, molecular biology, behavioural testing, electrophysiology understand how EWcp contributes alcohol consumption female versus male mice. Results Chemogenetic inhibition CART cells reduced binge specifically female, not Further, prevented ghrelin induced drinking, viral–mediated receptor ( Ghsr ) knockdown RNAscope revealed expression across peptidergic (marked by glutamatergic EWcp, with neurons from mice more sensitive bath application than Targeted GHSR signalling on peptidergic, mediate Finally, both inverse agonist antagonist delivered directly within Conclusions These findings suggest region mediating excessive bingeing through actions (CART-expressing) expand our understanding neural mechanism(s) underpinning system mediates consumption.

Language: Английский

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Neuromedin U Neurons in the Edinger–Westphal Nucleus Respond to Alcohol Without Interfering with the Urocortin 1 Response

Neurochemical Research, Journal Year: 2024, Volume and Issue: 49(12), P. 3277 - 3296

Published: Sept. 12, 2024

Language: Английский

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