Knockdown of GABAA alpha3 subunits on thalamic reticular neurons enhances deep sleep in mice

David S. Uygun; Chun Yang; Elena R. Tilli; Fumi Katsuki; Erik L. Hodges; James T. McKenna; James M. McNally; Ritchie E. Brown; Radhika Basheer

doi:10.1038/s41467-022-29852-x

Knockdown of GABA_A alpha3 subunits on thalamic reticular neurons enhances deep sleep in mice

David S. Uygun
, Chun Yang
, Elena R. Tilli
, Fumi Katsuki
, Erik L. Hodges
, James T. McKenna
, James M. McNally
, Ritchie E. Brown
, Radhika Basheer

Research output: Contribution to journal › Article › peer-review

Abstract

Identification of mechanisms which increase deep sleep could lead to novel treatments which promote the restorative effects of sleep. Here, we show that knockdown of the α3 GABA_A-receptor subunit from parvalbumin neurons in the thalamic reticular nucleus using CRISPR-Cas9 gene editing increased the thalamocortical delta (1.5–4 Hz) oscillations which are implicated in many health-promoting effects of sleep. Inhibitory synaptic currents in thalamic reticular parvalbumin neurons were strongly reduced in vitro. Further analysis revealed that delta power in long NREM bouts prior to NREM-REM transitions was preferentially affected by deletion of α3 subunits. Our results identify a role for GABA_A receptors on thalamic reticular nucleus neurons and suggest antagonism of α3 subunits as a strategy to enhance delta activity during sleep.

Original language	English
Article number	2246
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-29852-x
State	Published - Dec 2022
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2022, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

ASJC Scopus Subject Areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General
General Physics and Astronomy

Access to Document

10.1038/s41467-022-29852-x

Cite this

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title = "Knockdown of GABAA alpha3 subunits on thalamic reticular neurons enhances deep sleep in mice",

abstract = "Identification of mechanisms which increase deep sleep could lead to novel treatments which promote the restorative effects of sleep. Here, we show that knockdown of the α3 GABAA-receptor subunit from parvalbumin neurons in the thalamic reticular nucleus using CRISPR-Cas9 gene editing increased the thalamocortical delta (1.5–4 Hz) oscillations which are implicated in many health-promoting effects of sleep. Inhibitory synaptic currents in thalamic reticular parvalbumin neurons were strongly reduced in vitro. Further analysis revealed that delta power in long NREM bouts prior to NREM-REM transitions was preferentially affected by deletion of α3 subunits. Our results identify a role for GABAA receptors on thalamic reticular nucleus neurons and suggest antagonism of α3 subunits as a strategy to enhance delta activity during sleep.",

author = "Uygun, \{David S.\} and Chun Yang and Tilli, \{Elena R.\} and Fumi Katsuki and Hodges, \{Erik L.\} and McKenna, \{James T.\} and McNally, \{James M.\} and Brown, \{Ritchie E.\} and Radhika Basheer",

note = "Publisher Copyright: {\textcopyright} 2022, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.",

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doi = "10.1038/s41467-022-29852-x",

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TY - JOUR

T1 - Knockdown of GABAA alpha3 subunits on thalamic reticular neurons enhances deep sleep in mice

AU - Uygun, David S.

AU - Yang, Chun

AU - Tilli, Elena R.

AU - Katsuki, Fumi

AU - Hodges, Erik L.

AU - McKenna, James T.

AU - McNally, James M.

AU - Brown, Ritchie E.

AU - Basheer, Radhika

PY - 2022/12

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