Heterogeneous susceptibility of GABA(A) receptor-mediated IPSCs to depolarization-induced suppression of inhibition in rat hippocampus.

Depolarization-induced suppression of inhibition (DSI) in central neurons is mediated by a transient reduction of [gamma]-aminobutyric acid (GABA) release from interneurons. DSI is induced by a retrograde signal emitted from principal cells. We used electrophysiological recordings from CA1 neurons of the rat hippocampal slice to test the hypothesis that only certain classes of interneurons are susceptible to DSI. DSI of action potential-dependent, spontaneous, inhibitory postsynaptic currents (sIPSCs) in hippocampus is facilitated by carbachol (3 microM), which increases the occurrence of large sIPSCs. Besides carbachol, noradrenaline (norepinephrine; 10 microM), or elevated extracellular potassium (8 mM), could abruptly increase the occurrence of large sIPSCs and DSI in many cases. DSI appeared and disappeared concomitantly with the onset and offset of these large sIPSCs. In contrast, application of AP-5 and CNQX often markedly increased baseline sIPSC activity without enhancing DSI. A brief train of extracellular electrical stimulation could trigger the onset of prolonged, repetitive IPSC activity that was susceptible to DSI. The magnitude of DSI of single evoked IPSCs (eIPSCs) in a given pyramidal cell could be altered by changes in stimulus strength, but there was no simple relationship between stimulus strength and DSI. Baclofen (0.5-5 microM) eliminated the increase in sIPSC activity and DSI induced by carbachol. A GABA(B)receptor antagonist, CGP 35348, reversed the effects of baclofen. Carbachol-induced sIPSCs had relatively rapid rise and decay phases. There was no marked distinction between DSI-susceptible and non-susceptible sIPSCs. Nevertheless, two kinetically distinct components of the eIPSC could be distinguished by their decay times. DSI reduced GABA(A),(fast) without affecting GABA(A),(slow). Furosemide (frusemide), which blocks only GABA(A),(fast), reduced the eIPSC and occluded DSI. The data suggest that, with respect to DSI, there are at least three functionally distinct types of IPSCs. Two types (one susceptible to DSI and one not) have relatively rapid kinetics are probably made by perisomatic synapses. A third, slow IPSC, which is insensitive to DSI, may be produced by distal dendritic synapses.