Presynaptically "Silent" Synapses: Spontaneously Active Terminals without
Stimulus-Evoked Release Demonstrated in Cortical Autapses.
Fumitaka Kimura, Yo Otsu and Tadaharu Tsumoto.
Department of Neurophysiology, Biomedical Research Center, Osaka University
Medical School, 2-2 Yamadaoka, Suita 565 JAPAN.
APStracts 4:0023N, 1997.
ABSTRACT
This study addresses the question of whether synapses that are capable of
releasing transmitters spontaneously can also release them in an excitation-
dependent manner. For this purpose, whole cell patch recordings were performed
for a total of 48 excitatory solitary neurons in a microisland culture to
observe excitatory autaptic currents elicited by spontaneous transmitter
release as well as by somatic excitation. A somatic Na+-spike, induced in
response to a short voltage step, evoked excitatory postsynaptic currents
(EPSCs) of various amplitudes through the autapses; in some cases, no response
was noticeable. To make sure that the recorded autaptic spontaneous EPSCs
(sEPSCs) under a voltage-clamp resulted from independent release of
transmitters and were not associated with action potentials, sEPSCs in the
presence and absence of TTX were compared in six cells. In the presence of
TTX, the evoked EPSCs were completely eliminated, whereas the sEPSCs were
still observed and the amplitude distribution histograms were statistically
not different from those recorded in the absence of TTX. A quantitative
analysis of the sEPSCs (presumably miniature EPSCs) showed that the amplitude
of stimulus-evoked EPSCs did not correlate with the frequency or median
amplitudes of the sEPSCs, nor with the age of the culture. To identify whether
the absence of stimulus-evoked response was caused either by conduction
failure of excitation along the axons or by impairment of the release
machinery that links the terminal depolarization to vesicle exocytosis, we
examined whether high K+ and hypertonic solutions could facilitate the
spontaneous release of transmitters. Although the hypertonic solution
increased the spontaneous release in all cells tested (n=18), the high K+
solution had a differential effect in increasing spontaneous release, that is,
the cells with larger evoked responses were more readily facilitated by the
high K+ solution. Since the high K+ solution induces depolarization of
presynaptic terminals, the present results indicate that the smaller evoked
responses were due to the larger number of impaired or "silent" presynaptic
terminals that were unable to link presynaptic depolarization to transmitter
release. In summary, the present experiments provided evidence that at least
some of the presynaptic terminals are silent in response to stimuli, although
remaining spontaneously active at the same time. Since this phenomenon is due
to the lack of sensitivity to depolarization at the terminals, these synaptic
terminals seem incapable of linking terminal depolarization to transmitter
release.
Received 13 May 1996; accepted in final form 2 January 1996.
APS Manuscript Number J387-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 24 January 1997