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

Nature communications 2022 Apr 26

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

Citation

David S Uygun, Chun Yang, Elena R Tilli, Fumi Katsuki, Erik L Hodges, James T McKenna, James M McNally, Ritchie E Brown, Radhika Basheer. Knockdown of GABAA alpha3 subunits on thalamic reticular neurons enhances deep sleep in mice. Nature communications. 2022 Apr 26;13(1):2246