Forward genetics identifies a novel sleep mutant with sleep state inertia and REM sleep deficits.

ABSTRACT: Switches between global sleep and wakefulness states are believed to be dictated by top-down influences arising from subcortical nuclei. Using forward genetics and in vivo electrophysiology, we identified a recessive mouse mutant line characterized by a substantially reduced propensity to transition between wake and sleep states with an especially pronounced deficit in initiating rapid eye movement (REM) sleep episodes. The causative mutation, an Ile102Asn substitution in the synaptic vesicular protein, VAMP2, was associated with morphological synaptic changes and specific behavioral deficits, while in vitro electrophysiological investigations with fluorescence imaging revealed a markedly diminished probability of vesicular release in mutants. Our data show that global shifts in the synapt

SUBMITTER: Banks GT 

PROVIDER: S-EPMC7423362 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature