Aberrant synaptic release underlies sleep/wake transition deficits in a mouse Vamp2 mutant

Gareth T. Banks; Mathilde C. C. Guillaumin; Ines Heise; Petrina Lau; Minghui Yin; Nora Bourbia; Carlos Aguilar; Michael R. Bowl; Chris T. Esapa; Laurence A. Brown; Sibah Hasan; Erica Tagliatti; Elizabeth Nicholson; Rasneer Sonia Bains; Sara E. Wells; Vladyslav V. Vyazovskiy; Kirill E. Volynski; Stuart N. Peirson; Patrick M. Nolan

doi:10.1101/2020.01.09.900233

NeurosciencebioRxivJan 9, 2020

Preprint

Aberrant synaptic release underlies sleep/wake transition deficits in a mouse Vamp2 mutant

Gareth T. Banks iD, Mathilde C. C. Guillaumin iD, Ines Heise iD, Petrina Lau iD, Minghui Yin iD, Nora Bourbia iD, Carlos Aguilar iD, Michael R. Bowl iD, Chris T. Esapa, Laurence A. Brown iD, Sibah Hasan, Erica Tagliatti iD, Elizabeth Nicholson iD, Rasneer Sonia Bains iD, Sara E. Wells iD, Vladyslav V. Vyazovskiy iD, Kirill E. Volynski iD, Stuart N. Peirson iD, Patrick M. Nolan iD

Abstract

Sleep-wake transitions are modulated through extensive subcortical networks although the precise roles of their individual components remain elusive. Using forward genetics and in vivo electrophysiology, we identified a recessive mouse mutant line characterised by a reduced propensity to transition between all sleep states while a profound loss in total REM sleep time was evident. The causative mutation, an Ile102Asn substitution in VAMP2, was associated with substantial synaptic changes while in vitro electrophysiological investigations with fluorescence imaging revealed a diminished probability of vesicular release in mutants. We conclude that the synaptic efficiency of the entire subcortical brain network determines the likelihood that an animal transitions from one vigilance state to the next.

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