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Optogenetic identification of a rapid eye movement sleep modulatory circuit in the hypothalamus

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TLDR
Optogenetic tools suggest that activation of MCH neurons maintains REM sleep, possibly through inhibition of arousal circuits in the mammalian brain.
Abstract
Rapid-eye movement (REM) sleep correlates with neuronal activity in the brainstem, basal forebrain and lateral hypothalamus Lateral hypothalamus melanin-concentrating hormone (MCH)-expressing neurons are active during sleep, but their effects on REM sleep remain unclear Using optogenetic tools in newly generated Tg(Pmch-cre) mice, we found that acute activation of MCH neurons (ChETA, SSFO) at the onset of REM sleep extended the duration of REM, but not non-REM, sleep episodes In contrast, their acute silencing (eNpHR30, archaerhodopsin) reduced the frequency and amplitude of hippocampal theta rhythm without affecting REM sleep duration In vitro activation of MCH neuron terminals induced GABAA-mediated inhibitory postsynaptic currents in wake-promoting histaminergic neurons of the tuberomammillary nucleus (TMN), and in vivo activation of MCH neuron terminals in TMN or medial septum also prolonged REM sleep episodes Collectively, these results suggest that activation of MCH neurons maintains REM sleep, possibly through inhibition of arousal circuits in the mammalian brain

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References
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Journal ArticleDOI

Activity of norepinephrine-containing locus coeruleus neurons in behaving rats anticipates fluctuations in the sleep-waking cycle

TL;DR: The NE-LC system may globally bias the responsiveness of target neurons and thereby influence overall behavioral orientation, generally consistent with previous proposals that the NE- LC system is involved in regulating cortical and behavioral arousal.
Journal ArticleDOI

Multimodal fast optical interrogation of neural circuitry

TL;DR: An archaeal light-driven chloride pump from Natronomonas pharaonis is identified and developed for temporally precise optical inhibition of neural activity and forms a complete system for multimodal, high-speed, genetically targeted, all-optical interrogation of living neural circuits.
Journal Article

Multimodal fast optical interrogation of neural circuitry

TL;DR: In this paper, an archaeal light-driven chloride pump (NpHR) was developed for temporally precise optical inhibition of neural activity, allowing either knockout of single action potentials, or sustained blockade of spiking.
Journal ArticleDOI

Simple and highly efficient BAC recombineering using galK selection

TL;DR: Three new recombineering strains are described that allow bacterial artificial chromosomes (BACs) to be modified using galK positive/negative selection, and it is shown how galK selection can be used to rapidly introduce point mutations, deletions and loxP sites into BAC DNA and thus facilitate functional studies of SNP and/or disease-causing point mutations.
Journal ArticleDOI

Neural substrates of awakening probed with optogenetic control of hypocretin neurons

TL;DR: It is found that direct, selective, optogenetic photostimulation of Hcrt neurons increased the probability of transition to wakefulness from either slow wave sleep or rapid eye movement sleep.
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