The Journal of Neuroscience, March 1, 2002, 22(5):1942-1955
Persistent, Exocytosis-Independent Silencing of Release Sites
Underlies Homosynaptic Depression at Sensory Synapses in
Aplysia
Tony D.
Gover3,
Xue-Ying
Jiang1, and
Thomas
W.
Abrams1, 2, 3
Departments of 1 Pharmacology and
2 Anesthesiology and 3 Program in Neuroscience,
University of Maryland School of Medicine, Baltimore, Maryland
21201-1559
The synaptic connections of Aplysia sensory neurons
(SNs) undergo dramatic homosynaptic depression (HSD) with only a few
low-frequency stimuli. Strong and weak SN synapses, although differing
in their probabilities of release, undergo HSD at the same rate; this
suggests that the major mechanism underlying HSD in these SNs may not
be depletion of the releasable pool of vesicles. In computational models, we evaluated alternative mechanisms of HSD, including vesicle
depletion, to determine which mechanisms enable strong and weak
synapses to depress with identical time courses. Of five mechanisms
tested, only release-independent, stimulus-dependent switching off of
release sites resulted in HSD that was independent of initial synaptic
strength. This conclusion that HSD is a release-independent phenomenon
was supported by empirical results: an increase in Ca2+ influx caused by spike broadening with a
K+ channel blocker did not alter HSD. Once induced,
HSD persisted during 40 min of rest with no detectable recovery; thus,
release does not recover automatically with rest, contrary to what
would be expected if HSD represented an exhaustion of the exocytosis mechanism. The hypothesis that short-term HSD involves primarily a
stepwise silencing of release sites, rather than vesicle depletion, is
consistent with our earlier observation that HSD is accompanied by only
a modest decrease in release probability, as indicated by little change
in the paired-pulse ratio. In contrast, we found that there was a
dramatic decrease in the paired-pulse ratio during serotonin-induced
facilitation; this suggests that heterosynaptic facilitation primarily
involves an increase in release probability, rather than a change in
the number of functional release sites.
Key words:
synaptic depression; vesicle depletion; univesicular
release; computer simulations; silencing of release sites; serotonin-induced facilitation
Copyright © 2002 Society for Neuroscience 0270-6474/02/2251942-14$05.00/0
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