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: 1193-1215, 1999
Abstract
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.
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