Dual intracellular recordings and computational models of slow inhibitory postsynaptic potentials in rat neocortical and hippocampal slices.
Alex M. Thomson and Alain Destexhe

Neuroscience 92: 427-443, 1999

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Dual intracellular recordings in slices of adult rat neocortex and hippocampus investigated slow, putative GABAB receptor-mediated inhibitory postsynaptic potentials. In most pairs tested in which the interneuron elicited a fast inhibitory postsynaptic potential in the pyramid, this GABAA receptor mediated inhibitory postsynaptic potential was entirely blocked by bicuculline or picrotoxin (3:3 in neocortex, 6:8 in CA1, all CA1 basket cells), even when high-frequency presynaptic spike trains were elicited. However, in three of 85 neocortical paired recordings involving an interneuron, although no discernible response was elicited by single presynaptic interneuronal spikes, a long latency (>=20ms) inhibitory postsynaptic potential was elicited by a train of >=3 spikes at frequencies >=50-100Hz. This slow inhibitory postsynaptic potential was insensitive to bicuculline (one pair tested). In neocortex, slow inhibitory postsynaptic potential duration reached a maximum of 200ms even with prolonged presynaptic spike trains. In contrast, summing fast, GABAA inhibitory postsynaptic potentials, elicited by spike trains, lasted as long as the train. Between four and 10 presynaptic spikes, mean peak slow inhibitory postsynaptic potential amplitude increased sharply to 0.38, 2.6 and 2.9mV, respectively, in the three neocortical pairs (membrane potential -60 to -65mV). Thereafter increases in spike number had little additional effect on amplitude. In two of eight pairs in CA1, one involving a presynaptic basket cell and the other a putative bistratified interneuron, the fast inhibitory postsynaptic potential was blocked by bicuculline revealing a slow inhibitory postsynaptic potential that was greatly reduced by 100uM CGP 35348 (basket cell pair). The sensitivity of this slow inhibitory postsynaptic potential to spike number was similar to that of neocortical `pure’ slow inhibitory postsynaptic potentials, but was of longer duration, its plateau phase outlasting 200ms spike trains and its maximum duration exceeding 400ms. Computational models of GABA release, diffusion and uptake suggested that extracellular accumulation of GABA cannot alone account for the non-linear relationship between spike number and inhibitory postsynaptic potential amplitude. However, cooperativity in the kinetics of GABAB transduction mechanisms provided non-linear relations similar to experimental data. Different kinetic models were considered for how G-proteins activate K+ channels, including allosteric models. For all models, the best fit to experimental data was obtained with four G-protein binding sites on the K+ channels, consistent with a tetrameric structure for the K+ channels associated with GABAB receptors.

Thus some inhibitory connections in neocortex and hippocampus appear mediated solely by fast GABAA receptors, while others appear mediated solely by slow, non-ionotropic, possibly GABAB receptors. In addition, some inhibitory postsynaptic potentials arising in proximal portions of CA1 pyramidal cells are mediated by both GABAA and GABAB receptors. Our data indicate that the GABA released by a single interneuron can saturate the GABAB receptor mechanism(s) accessible to it and that `spillover’ to extrasynaptic sites need not necessarily be proposed to explain these slow inhibitory postsynaptic potential properties.