A Role for δ Subunit-Containing GABA _A Receptors on Parvalbumin-Positive Neurons in Maintaining Electrocortical Signatures of Sleep States

Abstract

GABA A receptors containing δ subunits have been shown to mediate tonic/slow inhibition in the CNS. These receptors are typically found extrasynaptically and are activated by relatively low levels of ambient GABA in the extracellular space. In the mouse neocortex, δ subunits are expressed by some pyramidal cells as well as on parvalbumin-positive (PV+) interneurons. An important function of PV+ interneurons is the organization of coordinated network activity that can be measured by EEG. However, it remains unclear what role tonic/slow inhibitory control of PV+ neurons may play in shaping oscillatory activity. After validating expected functional loss of δ-associated current in cortex of PV δcKO mice of both sexes, we performed EEG recordings to survey network activity across wake and sleep states. PV δcKO mice showed altered spectral content of EEG during NREM and REM sleep that was a result of increased oscillatory activity in NREM and the emergence of transient high-amplitude bursts of theta-frequency activity during REM. Viral reintroduction of Gabrd to PV+ interneurons in PV δcKO mice rescued REM EEG phenotypes, supporting an important role for δ subunit-mediated inhibition of PV+ interneurons for maintaining normal REM cortical oscillations.