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Sleep and Serotonin Modulate Paracapsular Nitric Oxide Synthase Expressing Neurons of the Amygdala

Lookup NU author(s): Dr Marco BocchioORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

Unraveling the roles of distinct neuron types is a fundamental challenge to understanding brain function in health and disease. In the amygdala, a brain structure regulating emotional behavior, the diversity of GABAergic neurons has been only partially explored. We report a novel population of GABAergic amygdala neurons expressing high levels of neuronal nitric oxide synthase (nNOS). These cells are predominantly localized along basolateral amygdala (BLA) boundaries. Performing ex vivo patch-clamp recordings from nNOS(+) neurons in Nos1-Cre(ER);Ai9 mice, we observed that nNOS(+) neurons located along the external capsule display distinctive electrophysiological properties, axonal and dendritic arborization, and connectivity. Examining their c-Fos expression, we found that paracapsular nNOS(+) neurons are activated during a period of undisturbed sleep following sleep deprivation, but not during sleep deprivation. Consistently, we found that dorsal raphe serotonin [5-hydroxytryptamine (5-HT)] neurons, which are involved in sleep-wake regulation, innervate nNOS(+) neurons. Bath application of 5-HT hyperpolarizes nNOS(+) neurons via 5-HT1A receptors. This hyperpolarization produces a reduction in firing rate and, occasionally, a switch from tonic to burst firing mode, thereby contrasting with the classic depolarizing effect of 5-HT on BLA GABAergic cells reported so far. Thus, nNOS(+) cells are a distinct cell type of the amygdala that controls the activity of downstream neurons in both amygdaloid and extra-amygdaloid regions in a vigilance state-dependent fashion. Given the strong links among mood, sleep deprivation, and 5-HT, the recruitment of paracapsular nNOS(+) neurons following high sleep pressure may represent an important mechanism in emotional regulation.


Publication metadata

Author(s): Bocchio M, Fisher SP, Unal G, Ellender TJ, Vyazovskiy VV, Capogna M

Publication type: Article

Publication status: Published

Journal: eNeuro

Year: 2016

Volume: 37

Issue: 5

Online publication date: 26/09/2016

Acceptance date: 12/09/2016

Date deposited: 04/05/2021

ISSN (electronic): 2373-2822

Publisher: Society for Neuroscience

URL: https://doi.org/10.1523/ENEURO.0177-16.2016

DOI: 10.1523/ENEURO.0177-16.2016


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