F. Kimura et al., PRESYNAPTICALLY SILENT SYNAPSES - SPONTANEOUSLY ACTIVE TERMINALS WITHOUT STIMULUS-EVOKED RELEASE DEMONSTRATED IN CORTICAL AUTAPSES, Journal of neurophysiology, 77(5), 1997, pp. 2805-2815
This study addresses the question of whether synapses that are capable
of releasing transmitters spontaneously can also release them in an e
xcitation-dependent manner. For this purpose, whole cell patch recordi
ngs were performed for a total of 48 excitatory solitary neurons in a
microisland culture to observe excitatory autaptic currents elicited b
y 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 throug
h the autapses; in some cases, no response was noticeable. To make sur
e that the recorded autaptic spontaneous EPSCs (sEPSCs) under a voltag
e clamp resulted from independent release of transmitters and were not
associated with action potentials, sEPSCS in the presence and absence
of tetrodotoxin (TTX) were compared in six cells. In the presence of
TTX the evoked EPSCs were completely eliminated, whereas the sEPSCs we
re still observed and the amplitude distribution histograms were stati
stically not different from those recorded in the absence of TTX. A qu
antitative analysis of the sEPSCs (presumably miniature EPSCs) showed
that the amplitude of stimulus-evoked EPSCs did not correlate with eit
her the frequency or median amplitudes of the sEPSCs or 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 depo
larization to vesicle exocytosis, we examined whether high K+ and hype
rtonic solutions could facilitate the spontaneous release of transmitt
ers. Although the hypertonic solution increased the spontaneous releas
e in all cells tested (n = 18), the high K+ solution had a differentia
l effect in increasing spontaneous release, i.e., the cells with large
r evoked responses were more readily facilitated by the high K+ soluti
on. Because the high K+ solution induced depolarization of presynaptic
terminals, the present results indicated that the smaller evoked resp
onses were due to the lar er number of impaired or ''silent'' presynap
tic a terminals that were unable to link presynaptic depolarization to
transmitter release. In summary, the present experiments provided evi
dence that at least some of the presynaptic terminals are silent in re
sponse to stimuli, while remaining spontaneously active at the same ti
me. Because this phenomenon is due to the lack of sensitivity to depol
arization at the terminals, these synaptic terminals seem incapable of
linking terminal depolarization to transmitter release.