title: Multimodal quantal release at individual hippocampal synapses: evidence for no lateral inhibition.
abstract: Most CNS synapses investigated thus far contain a large number of vesicles docked at the active zone, possibly forming individual release sites. At the present time, it is unclear whether these vesicles can be discharged independently of one another. To investigate this problem, we recorded miniature excitatory currents by whole-cell and single-synapse recordings from CA3-CA1 hippocampal neurons and analyzed their stochastic properties. In addition, spontaneous release was investigated by ultrastructural analysis of quickly frozen synapses, revealing vesicle intermediates in docking and spontaneous fusion states. In these experiments, no signs of inhibitory interactions between quanta could be detected up to 1 msec from the previous discharge. This suggests that exocytosis at one site does not per se inhibit vesicular fusion at neighboring sites. At longer intervals, the output of quanta diverged from a random memoryless Poisson process because of the presence of a bursting component. The latter, which could not be accounted for by random coincidences, was independent of Ca2+ elevations in the cytosol, whether from Ca2+ flux through the plasma membrane or release from internal stores. Results of these experiments, together with the observation of spontaneous pairs of omega profiles at the active zone, suggest that multimodal release is produced by an enduring activation of an integrated cluster of release sites.
authors.affiliation: Unit of Neurobiology, Università Vita-Salute San Raffaele, Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Abenavoli
authors.forename: Lia
authors.initials: L
authors.lastname: Forti
authors.forename: Mario
authors.initials: M
authors.lastname: Bossi
authors.forename: Andrea
authors.initials: A
authors.lastname: Bergamaschi
authors.forename: Antonello
authors.initials: A
authors.lastname: Villa
authors.forename: Antonio
authors.initials: A
authors.lastname: Malgaroli
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology; D005089:Exocytosis / Q000502:physiology; D005614:Freeze Fracturing; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D008561:Membrane Fusion / Q000502:physiology; D009010:Monte Carlo Method; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D016012:Poisson Distribution; D017729:Presynaptic Terminals / Q000378:metabolism; D051381:Rats; D011930:Reaction Time / Q000502:physiology; D012815:Signal Processing, Computer-Assisted; D013269:Stochastic Processes; D013569:Synapses / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013572:Synaptic Vesicles / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002614:Chelating Agents; D002118:Calcium