title: Independent regulation of basal neurotransmitter release efficacy by variable Ca²+ influx and bouton size at small central synapses.
abstract: The efficacy of action potential evoked neurotransmitter release varies widely even among synapses supplied by the same axon, and the number of release-ready vesicles at each synapse is a major determinant of this heterogeneity. Here we identify a second, equally important, mechanism for release heterogeneity at small hippocampal synapses, the inter-synaptic variation of the exocytosis probability of release-ready vesicles. Using concurrent measurements of vesicular pool sizes, vesicular exocytosis rates, and presynaptic Ca²⁺ dynamics, in the same small hippocampal boutons, we show that the average fusion probability of release-ready vesicles varies among synapses supplied by the same axon with the size of the spike-evoked Ca²⁺ concentration transient. We further show that synapses with a high vesicular release probability exhibit a lower Ca²⁺ cooperativity, arguing that this is a direct consequence of increased Ca²⁺ influx at the active zone. We conclude that variability of neurotransmitter release under basal conditions at small central synapses is accounted for not only by the number of release-ready vesicles, but also by their fusion probabilities, which are set independently of bouton size by variable spike-evoked presynaptic Ca²⁺ influx.
authors.affiliation: UCL Institute of Neurology, University College London, United Kingdom.
authors.forename: Yaroslav S
authors.initials: YS
authors.lastname: Ermolyuk
authors.forename: Felicity G
authors.initials: FG
authors.lastname: Alder
authors.forename: Christian
authors.initials: C
authors.lastname: Henneberger
authors.forename: Dmitri A
authors.initials: DA
authors.lastname: Rusakov
authors.forename: Dimitri M
authors.initials: DM
authors.lastname: Kullmann
authors.forename: Kirill E
authors.initials: KE
authors.lastname: Volynski
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001369:Axons / Q000378:metabolism; D002021:Buffers; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D005089:Exocytosis; D005453:Fluorescence; D018377:Neurotransmitter Agents / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism*; D051381:Rats; D013569:Synapses / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism
chemical_list: D002021:Buffers; D018377:Neurotransmitter Agents; D002118:Calcium