The Journal of Neuroscience, August 1, 2002, 22(15):6336-6346
Multimodal Quantal Release at Individual Hippocampal Synapses:
Evidence for No Lateral Inhibition
Alessandra
Abenavoli1,
Lia
Forti1,
Mario
Bossi2,
Andrea
Bergamaschi1,
Antonello
Villa2, and
Antonio
Malgaroli1
1 Unit of Neurobiology, Università Vita-Salute
San Raffaele, Milan, Italy 20132, and 2 Microscopy and
Image Analysis Center, Medical School University Bicocca, Milan, Italy
20052
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.
Key words:
central synapses; exocytosis; miniature
excitatory currents; stochastic properties; multivesicular release; hippocampus
Copyright © 2002 Society for Neuroscience 0270-6474/02/22156336-11$05.00/0