TY - JOUR
T1 - Forward genetics identifies a novel sleep mutant with sleep state inertia and REM sleep deficits
AU - Banks, Gareth T.
AU - Guillaumin, Mathilde C.C.
AU - Heise, Ines
AU - Lau, Petrina
AU - Yin, Minghui
AU - Bourbia, Nora
AU - Aguilar, Carlos
AU - Bowl, Michael R.
AU - Esapa, Chris
AU - Brown, Laurence A.
AU - Hasan, Sibah
AU - Tagliatti, Erica
AU - Nicholson, Elizabeth
AU - Bains, Rasneer Sonia
AU - Wells, Sara
AU - Vyazovskiy, Vladyslav V.
AU - Volynski, Kirill
AU - Peirson, Stuart N.
AU - Nolan, Patrick M.
N1 - Publisher Copyright:
© 2020 The Authors
PY - 2020/8
Y1 - 2020/8
N2 - 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 synaptic efficiency across brain-wide networks leads to an altered probability of vigilance state transitions, possibly as a result of an altered excitability balance within local circuits controlling sleep-wake architecture.
AB - 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 synaptic efficiency across brain-wide networks leads to an altered probability of vigilance state transitions, possibly as a result of an altered excitability balance within local circuits controlling sleep-wake architecture.
UR - http://www.scopus.com/inward/record.url?scp=85089967644&partnerID=8YFLogxK
U2 - 10.1126/sciadv.abb3567
DO - 10.1126/sciadv.abb3567
M3 - Article
C2 - 32851175
AN - SCOPUS:85089967644
SN - 2375-2548
VL - 6
JO - Science Advances
JF - Science Advances
IS - 33
M1 - eabb3567
ER -