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

• Main Authors: Basheer, R. (Author), Brown, R.E (Author), Hodges, E.L (Author), Katsuki, F. (Author), McKenna, J.T (Author), McNally, J.M (Author), Tilli, E.R (Author), Uygun, D.S (Author), Yang, C. (Author)
• Format: Article
• Language: English
• Published: NLM (Medline) 2022
• Online Access: View Fulltext in Publisher
• ISBN: 20411723 (ISSN)
• DOI: 10.1038/s41467-022-29852-x

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.