THE DYNAMICS OF SYNCHRONIZED NEUROTRANSMITTER RELEASE DETERMINED FROMCOMPOUND SPONTANEOUS IPSCS IN RAT DENTATE GRANULE NEURONS IN-VITRO

1. The properties of GAB(A), receptor-mediated spontaneous IPSCs gener ated in hippocampal dentate granule neurones were analysed using whole -cell voltage-clamp techniques in order to explore the functional cons equences of the low number (6-12) and close proximity of synaptic cont acts made by single GABAergic interneurones. 2. Spontaneous IPSCs (sIP SCs) occurred with a frequency of 14.0 +/- 9.1 Hz (n = 31)and revealed a multi-modal positively skewed amplitude distribution (39.0 +/- 19.8 pA, median values). 3. The variance of 10-90% rise times and decay ki netics between IPSCs decreased with increasing peak amplitude. Larger amplitude events had significantly faster rise times, consistent with their site of generation being proximal to the soma. The decay kinetic s of sIPSCs did not significantly change with amplitude. 4. Large ampl itude sIPSCs occurred singularly or in discrete bursts, repeated regul arly at low frequency. The rising phase of such sIPSCs were multi-phas ic, composed of clear steplike inflections that were not a product of noise. The variability between the rising phase of individual sIPSCs w as quantified by calculating their standard deviation, which produced fast rising (0.22 +/- 0.05 ms time to peak, n = 16) functions with hal f-widths of 0.38 +/- 0.10 ms, which declined to plateaux. 5. Computer simulations demonstrated that IPSCs with properties similar to those r ecorded experimentally could be generated by the linear summation of g roups of temporally dispersed component events. Standard deviation fun ctions of the rising phase of simulated IPSCs accurately described dis tributions of the temporal dispersion of unitary components. 6. The GA BA uptake inhibitor (R)-N-[4,4-bis(3-methyl-2-thienyl)but-3-enl-yl] ni pecotic acid (tiagabine) (10 M, n = 12) significantly prolonged the de cay of mIPSCs (6.5 +/- 0.8 to 8.7 +/- 1.0 ms, median values) and sIPSC s (6.2 +/- 0.4 to 7.3 +/- 1.2 ms, median values), but failed to alter the frequency of occurrence, 10-90% rise times or peak amplitude of ev ents. The application of flurazepam (30 mu M, n = 7; 50 mu M, n = 4) p rolonged the decay of sIPSCs regardless of their amplitude. 7. These d ata indicate that sIPSCs are formed by the summation of unitary compon ents that occur asynchronously and that GABA released from multiple si tes has independent postsynaptic actions.