The effects of trimethyltin (TMT) on passive properties and synaptic activity of dentate granule cell (GC) have been investigated in hippocampal slices in vitro. Intracellular recordings from GC indicated that TMT (1 and 10 microM) increased input resistance from 34.1 +/- 3.6 Mohms to 45.6 +/- 4.1 and 64.7 +/- 14.7 Mohms, respectively, 15 min after its application. This was accompanied by a 10-20 mV depolarization. A decrease in IPSP amplitude was also observed, but developed with longer delays (2-4 hr) following TMT exposure. Extracellular recording from the GC layer during paired pulse stimulation of the perforant path showed a decrease in the ratio of the amplitude of the first to the second population spikes (at an interpulse interval of 9 msec), from 1.8 +/- 0.14 to 0.8 +/- 0.08 (p less than 0.05). The amplitude of the first (conditioning) pulse remained unchanged, suggesting that TMT produced a specific decrease of inhibitory efficacy. These results add evidence to the hypothesis that TMT neurotoxicity is mediated by a decrease of inhibitory synaptic functions
