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Knockdown of GABA_A 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 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.

SUBMITTER: Uygun DS

PROVIDER: S-EPMC9042958 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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

Uygun David S DS Yang Chun C Tilli Elena R ER Katsuki Fumi F Hodges Erik L EL McKenna James T JT McNally James M JM Brown Ritchie E RE Basheer Radhika R

Nature communications 20220426 1

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 str ...[more]

PMID: 35473906

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