title: Vesicles derived via AP-3-dependent recycling contribute to asynchronous release and influence information transfer.
abstract: Action potentials trigger synchronous and asynchronous neurotransmitter release. Temporal properties of both types of release could be altered in an activity-dependent manner. While the effects of activity-dependent changes in synchronous release on postsynaptic signal integration have been studied, the contribution of asynchronous release to information transfer during natural stimulus patterns is unknown. Here we find that during trains of stimulations, asynchronous release contributes to the precision of action potential firing. Our data show that this form of release is selectively diminished in AP-3b2 KO animals, which lack functional neuronal AP-3, an adaptor protein regulating vesicle formation from endosomes generated during bulk endocytosis. We find that in the absence of neuronal AP-3, asynchronous release is attenuated and the activity-dependent increase in the precision of action potential timing is compromised. Lack of asynchronous release decreases the capacity of synaptic information transfer and renders synaptic communication less reliable in response to natural stimulus patterns.
authors.affiliation: Department of Psychiatry and Neuroscience, Quebec Mental Health Institute, Université Laval, Quebec City, Quebec, Canada G1J 2G3.
authors.forename: Alesya
authors.initials: A
authors.lastname: Evstratova
authors.affiliation: Department of Psychiatry and Neuroscience, Quebec Mental Health Institute, Université Laval, Quebec City, Quebec, Canada G1J 2G3.
authors.forename: Simon
authors.initials: S
authors.lastname: Chamberland
authors.affiliation: Department of Cell Biology, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Victor
authors.initials: V
authors.lastname: Faundez
authors.affiliation: Department of Psychiatry and Neuroscience, Quebec Mental Health Institute, Université Laval, Quebec City, Quebec, Canada G1J 2G3.
authors.forename: Katalin
authors.initials: K
authors.lastname: Tóth
mesh_terms: D000200:Action Potentials; D033963:Adaptor Protein Complex 3 / Q000235:genetics* / Q000378:metabolism; D033966:Adaptor Protein Complex beta Subunits / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009435:Synaptic Transmission; D013572:Synaptic Vesicles / Q000378:metabolism*
chemical_list: C000602624:AP-3b2 adaptor protein, mouse; D033963:Adaptor Protein Complex 3; D033966:Adaptor Protein Complex beta Subunits