Tsugorka T. Mechanisms of delayed inhibitory synaptic currents evoked by high frequency stimulation in cultural hippocampal neurons

Synaptic GABAA receptors in hippocampus are known to be highly heterogenous thus to be activated differently in response to various patterns of activity. Here we compared the groups of postsynaptic GABAA receptors involved in generation of early and late phases of the synaptic response to short trains of 5 to 20 pulses delivered at 2-100 Hz, imitating natural patterns of cortical interneuronal activity. Initially we have shown that GABAA receptors selective antagonist picrotoxin blocks active synaptic receptors much faster. When picrotoxin was applied simultaneously with the low-frequency stimulation, the early phase of synaptic response was suppressed on average 1.8 times more than the late one. We conclude that there is a group of receptors generating no less than 65.4±6.9% of the late-phase curent but no more than 36.4±4.2% of the early one. Long-term picrotoxin application blocked both phases equally. Desensitization nonuniformity was shown could contribute to the observed differences beween groups of receptors but it could provide less then a half of the observed effect. Model - based analysis showed that it could also originate from nonuniform spatial distribution of the synaptic GABAA receptors with respect to synaptic release sites. The subunit composition of receptors was found to be the same for both groups at least at a half of synapses. Discovered differences between groups of GABAA receptors can possibly serve for conversion of synapses nonuniformity into the diversity of the synaptic response forms. Keywords: GABAergic synaptic transmission, asynchronous transmitter release, synaptic plasticity, picrotoxin, desensitisation