First Author | Uygun DS | Year | 2022 |
Journal | Nat Commun | Volume | 13 |
Issue | 1 | Pages | 2246 |
PubMed ID | 35473906 | Mgi Jnum | J:358954 |
Mgi Id | MGI:7265915 | Doi | 10.1038/s41467-022-29852-x |
Citation | Uygun DS, et al. (2022) Knockdown of GABAA alpha3 subunits on thalamic reticular neurons enhances deep sleep in mice. Nat Commun 13(1):2246 |
abstractText | 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 alpha3 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 alpha3 subunits. Our results identify a role for GABAA receptors on thalamic reticular nucleus neurons and suggest antagonism of alpha3 subunits as a strategy to enhance delta activity during sleep. |