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Publication : Knockdown of GABA(A) alpha3 subunits on thalamic reticular neurons enhances deep sleep in mice.

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.
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