The GABA-content of central inhibitory synapses can be up- or downregulated in different (patho)-physiological situations. In order to assess whether such plastic changes occur at physiological levels of activity we recorded miniature inhibitory postsynaptic currents (mIPSCs) in CA1 pyramidal cells after strong afferent stimulation of the Schaffer collaterals (1s, 100 Hz).

Stable mIPSC amplitudes were obtained in unstimulated control slices for 1 hour. Stimulation caused a significant increase in mIPSC amplitude by ~70%. We hypothezised that this increase was due to increased vesicular GABA content. The amplitude increase of mIPSCs could be reduced by blocking neuronal glutamate uptake (TBOA) and was completely prevented when both glutamate- and GABA-uptake were blocked [(+ NCC-711). These data show a contribution of extracellular glutamate-and GABA-levels to vesicular GABA content. Consistently, block of glutamate-and GABA-uptake in unstimulated tissue led to a slow progressive decline in mIPSC amplitude. Our data indicate that vesicular GABA content is regulated in an activity-dependent manner by two sources: i)] uptake of glutamate (with subsequent decarboxylation; ii) direct uptake of GABA.

Supported by SFB 488 and Forschergruppe 577 (DFG)