PRESYNAPTICALLY SILENT SYNAPSES - SPONTANEOUSLY ACTIVE TERMINALS WITHOUT STIMULUS-EVOKED RELEASE DEMONSTRATED IN CORTICAL AUTAPSES

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.