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

• DOI: 10.1038/s41467-022-29852-x
• Publication Date: 2022-04-26T10:09:28Z
• Authors: David S. Uygun; Chun Yang; Elena R. Tilli; Fumi Katsuki; Erik L. Hodges; James T. McKenna; James M. McNally; Ritchie E. Brown; Radhika Basheer
• Keywords: Neurons; Science; Q; Receptors, GABA-A; Sleep, Slow-Wave; Article; Mice; 03 medical and health sciences; Parvalbumins; 0302 clinical medicine; Thalamus; Animals; gamma-Aminobutyric Acid

AbstractIdentification 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.