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Volume 16, Number 17,
Issue of September 1, 1996
pp. 5312-5323
Copyright ©1996 Society for Neuroscience
Calcium-Dependent Paired-Pulse Facilitation of Miniature EPSC
Frequency Accompanies Depression of EPSCs at Hippocampal Synapses in
Culture
Received April 29, 1996; revised June 3, 1996; accepted June 5, 1996.
Dana D. Cummings1,
Karen S. Wilcox2, and
Marc
A. Dichter1, 2, 3
1 David Mahoney Institute of Neurological Sciences and
2 Departments of Neurology and 3 Pharmacology,
School of Medicine, University of Pennsylvania, Philadelphia,
Pennsylvania 19104
Two forms of evoked neurotransmitter release at excitatory synapses
between cultured hippocampal neurons have been described. After an
action potential, it has been shown that transmitter initially is
released synchronously, and this is followed by a period of ``slow''
asynchronous release. The ``fast'' synchronous component of release
at these synapses has been found routinely to demonstrate paired-pulse
and tetanic depression, whereas the short-term plasticity of
asynchronous release has not been investigated. In the present
experiments, we have used the whole-cell patch-clamp technique to
record from pairs of neurons in a low-density hippocampal culture
preparation to determine both the properties and underlying mechanisms
of short-term plasticity of asynchronous release. It was found that an
increase in miniature EPSC (mEPSC) frequency accompanied both single
and multiple stimuli, and this mEPSC increase was facilitated during
paired stimuli, even when the evoked synchronous release was depressed.
In addition, both the activity-dependent depression of evoked
EPSCs and facilitation of asynchronous mEPSC release were dependent on
Ca accumulation in the nerve terminal. However, the Ca-dependent
mechanisms underlying these two processes could be distinguished by the
differential effects of two membrane-permeant calcium chelators,
BAPTA-AM and EGTA-AM. Frequency-dependent depression of evoked EPSCs
involves a rapid rise in intraterminal Ca, which likely triggers a
process that proceeds in a Ca-independent manner, whereas the
asynchronous release may be linked more directly to a sustained
increase in intraterminal Ca.
Key words:
mEPSC;
synaptic plasticity;
BAPTA-AM;
EGTA-AM;
hippocampal culture;
paired-pulse facilitation;
paired-pulse
depression
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