The Journal of Neurophysiology Vol. 77 No. 5 May 1997, pp. 2805-2815
Copyright ©1997 The American Physiological Society

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, Suita 565, Japan

Kimura, Fumitaka, Yo Otsu, and Tadaharu Tsumoto. Presynaptically silent synapses: spontaneously active terminals without stimulus-evoked release demonstrated in cortical autapses. J. Neurophysiol. 77: 2805-2815, 1997. 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 tetrodotoxin (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 either 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 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, i.e., the cells with larger evoked responses were more readily facilitated by the high K⁺ solution. Because the high K⁺ solution induced depolarization of presynaptic terminals, the present results indicated 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, while remaining spontaneously active at the same time. Because 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.

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