A noradrenergic-hypothalamic neural substrate for stress-induced sleep disturbances

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(45)

Published: Nov. 4, 2022

In our daily life, we are exposed to uncontrollable and stressful events that disrupt sleep. However, the underlying neural mechanisms deteriorating quality of non-rapid eye movement sleep (NREMs) REM largely unknown. Here, show in mice acute psychosocial stress disrupts by increasing brief arousals (microarousals [MAs]), reducing spindles, impairing infraslow oscillations spindle band electroencephalogram during NREMs, while REMs. This poor was reflected an increased number calcium transients activity noradrenergic (NE) neurons locus coeruleus (LC) NREMs. Opto- chemogenetic LC-NE activation naïve is sufficient change microarchitecture similar stress. Conversely, chemogenetically inhibiting reduced MAs NREMs normalized their after Specifically projecting preoptic area hypothalamus (POA) decreased enhanced spindles REMs Optrode recordings revealed stimulating fibers POA indeed suppressed spiking activated inactivated MAs. Our findings reveal changes dynamics stress-regulatory negatively affect quality, partially through interaction with POA.

Language: Английский

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Prefrontal cortical regulation of REM sleep

Nature Neuroscience, Journal Year: 2023, Volume and Issue: 26(10), P. 1820 - 1832

Published: Sept. 21, 2023

Language: Английский

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Somatostatin neurons in prefrontal cortex initiate sleep-preparatory behavior and sleep via the preoptic and lateral hypothalamus

Nature Neuroscience, Journal Year: 2023, Volume and Issue: 26(10), P. 1805 - 1819

Published: Sept. 21, 2023

The prefrontal cortex (PFC) enables mammals to respond situations, including internal states, with appropriate actions. One such state could be 'tiredness'. Here, using activity tagging in the mouse PFC, we identified particularly excitable, fast-spiking, somatostatin-expressing, γ-aminobutyric acid (GABA) (PFC

Language: Английский

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The neural basis of resting-state fMRI functional connectivity in fronto-limbic circuits revealed by chemogenetic manipulation

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 31, 2024

Abstract Measures of fMRI resting-state functional connectivity (rs-FC) are an essential tool for basic and clinical investigations fronto-limbic circuits. Understanding the relationship between rs-FC underlying patterns neural activity in these circuits is therefore vital. Here we introduced inhibitory designer receptors exclusively activated by drugs (DREADDs) into amygdala two male macaques. We evaluated causal effect activating DREADD on within connecting frontal cortex. Activating increased ventrolateral prefrontal Neurophysiological recordings revealed that DREADD-induced increase was associated with local field potential coherency alpha band (6.5–14.5 Hz) Thus, our multi-modal approach reveals specific signature neuronal underlies

Language: Английский

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Mesolimbic dopamine neurons drive infradian rhythms in sleep-wake and heightened activity state

Science Advances, Journal Year: 2025, Volume and Issue: 11(1)

Published: Jan. 1, 2025

Infradian mood and sleep-wake rhythms with periods of 48 hours beyond have been observed in patients bipolar disorder (BD), which even persist the absence exogenous timing cues, indicating an endogenous origin. Here, we show that mice exposed to methamphetamine drinking water develop infradian locomotor extend sleep length manic state–associated behaviors support a model for cycling BD. The capacity is abrogated upon genetic disruption dopamine (DA) production DA neurons ventral tegmental area (VTA) or ablation nucleus accumbens projecting neurons. Furthermore, chemogenetic activation VTA including those project led period lengthening circadian clock–deficient mice, was counteracted by antipsychotic treatment. Together, our findings argue BD relies on rhythm generation depends mesolimbic

Language: Английский

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A medullary hub for controlling REM sleep and pontine waves

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: July 3, 2023

Abstract Rapid-eye-movement (REM) sleep is a distinct behavioral state associated with vivid dreaming and memory processing. Phasic bursts of electrical activity, measurable as spike-like pontine (P)-waves, are hallmark REM implicated in consolidation. However, the brainstem circuits regulating P-waves, their interactions generating sleep, remain largely unknown. Here, we show that an excitatory population dorsomedial medulla (dmM) neurons expressing corticotropin-releasing-hormone (CRH) regulates both P-waves mice. Calcium imaging showed dmM CRH selectively activated during recruited opto- chemogenetic experiments revealed this promotes sleep. Chemogenetic manipulation also induced prolonged changes P-wave frequency, while brief optogenetic activation reliably triggered along transiently accelerated theta oscillations electroencephalogram (EEG). Together, these findings anatomically functionally delineate common medullary hub for regulation P-waves.

Language: Английский

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Neocortical long-range inhibition promotes cortical synchrony and sleep

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

Published: June 23, 2024

Behavioral states such as sleep and wake are highly correlated with specific patterns of rhythmic activity in the cortex. During low arousal slow wave sleep, cortex is synchronized dominated by frequency rhythms coordinated across multiple regions. Although recent evidence suggests that GABAergic inhibitory neurons key players cortical state modulation,

Language: Английский

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SEX-DEPENDENT MODULATION OF BEHAVIORAL ALLOCATION VIA VENTRAL TEGMENTAL AREA-NUCLEUS ACCUMBENS SHELL CIRCUITRY

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 10, 2025

Diagnostic criteria for substance use disorder, cocaine type (i.e., disorder), outlined in the 5 th edition of and Statistical Manual, imply that disorder arises, at least part, from maladaptive allocation behavior to drug use. To date, however, neural circuits involved have not been systematically evaluated. Herein, a chemogenetics approach designer receptors exclusively activated by drugs (DREADDs)) was utilized combination with concurrent choice self-administration experimental paradigm evaluate role mesolimbic neurocircuit behavior. Pharmacological activation hM3D(G q ) DREADDs neurons projecting ventral tegmental area (VTA) nucleus accumbens (AcbSh) induced sex-dependent shift rodents transduced DREADDs. Specifically, male animals exhibited robust increase responding natural sucrose) reward following pharmacological VTA-AcbSh circuit; female rodents, sharp contrast, displayed prominent decrease drug-reinforced cocaine) responding. The sequential KORD within same neuronal population validated circuit reinforced concurrently available rewards. Collectively, is fundamentally behavioral affording key target development novel pharmacotherapies.

Language: Английский

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Chemogenetic inhibition of corticotropin releasing hormone neurons in the paraventricular nucleus attenuates traumatic stress-induced deficit of NREM sleep, but not REM sleep in mice

Stress, Journal Year: 2025, Volume and Issue: 28(1)

Published: Feb. 16, 2025

Present study was aimed to elucidate the role of corticotropin releasing hormone (CRH) neurons located in paraventricular nucleus hypothalamus (PVN) mechanisms stress-induced insomnia. Experiments were done rodent model traumatic stress, mice exposure predator (rat) odor. Sleep changes associated with this stress first assessed adult male C57BL/6J wild-type (n = 12). The effect chemogenetic silencing CRH within PVN on insomnia examined CRH-ires-Cre using designer receptors exclusively activated by drugs (DREADD) technology. Animals received bilateral injections inhibitory DREADD vector AAV-hSyn-DIO-hM4Di-mCherry 10) or control AAV-hSyn-DIO-mCherry virus into during surgery. intraperitoneal injection clozapine-N-oxide (CNO) prior induction stress. rat odor induced strong long-lasting suppression both non-rapid eye movement (NREM) and rapid (REM) sleep stages experiments. Selective alleviated acute significantly increasing time spent NREM but it did not counteract deficit REM sleep. These findings suggest a specific for CRH-secreting caused whereas is controlled different mechanism.

Language: Английский

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Neuronal PAS domain 1 identifies a major subpopulation of wakefulness-promoting GABAergic neurons in the basal forebrain

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(21)

Published: May 15, 2024

Here, we describe a group of basal forebrain (BF) neurons expressing neuronal Per-Arnt-Sim (PAS) domain 1 (Npas1), developmental transcription factor linked to neuropsychiatric disorders. Immunohistochemical staining in Npas1-cre-2A-TdTomato mice revealed BF Npas1 + are distinct from well-studied parvalbumin or cholinergic neurons. GAD67-GFP knock-in confirmed that the vast majority GABAergic, with minimal colocalization glutamatergic vGlut1-cre-tdTomato vGlut2-cre-tdTomato mice. The density was high, five six times neighboring cholinergic, parvalbumin, Anterograde tracing identified prominent projections brain regions involved sleep–wake control, motivated behaviors, and olfaction such as lateral hypothalamus, habenula, nucleus accumbens shell, ventral tegmental area, olfactory bulb. Chemogenetic activation light period increased amount wakefulness latency sleep for 2 3 h, due an increase long wake bouts short NREM bouts. slow-wave sigma power, well spindle density, amplitude, duration, were reduced, reminiscent findings several Together previous implicating stress responsiveness, anatomical effect activating them suggest possible role motivationally driven stress-induced insomnia. Identification this major subpopulation GABAergic will facilitate studies their disorders, dementia, other conditions involving BF.

Language: Английский

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