Paired pulse depression (PPD) of GABA-ergic IPSC was studied in rat hippocampal cell cultures. Synaptic responses were evoked by local extracellular stimulation of the presynaptic units; a whole-cell patch-clamp technique was employed to record responses (IPSC) from the postsynaptic neurons. Paired stimulation (100-msec-long interstimulus interval) resulted in depression of the second IPSC amplitude (IPSC2). This was usually accompanied by an increase in the coefficient of variation of IPSC2 comparing with that of IPSC1. These results support the involvement of presynaptic mechanism(s) in PPD and suggest a possibility to use PPD alteration as an indicator for the presynaptic origin of modulatory effects. To check this suggestion, we tested whether alteration of the quantum content would affect PPD. We found that reduction of the transmitter release by application of <$E roman Cd sup 2+> decreased PPD. Post-tetanic potentiation, a well-established presynaptic phenomenon, increased PPD. We conclude that PPD changes may be used as a test for the involvement of presynaptic changes.

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