The Synaptic Basis of GABAA,slow

Abstract

Although two kinetically distinct evoked GABA A responses (GABA A,fast and GABA A,slow) have been observed in CA1 pyramidal neurons, studies of spontaneous IPSCs (sIPSCs) in these neurons have reported only a single population of events that resemble GABA A,fast in their rise and decay kinetics. The absence of slow sIPSCs calls into question the synaptic basis of GABA A,slow. We present evidence here that both evoked responses are synaptic in origin, because two classes of minimally evoked, spontaneous and miniature IPSCs exist that correspond to GABA A,fast and GABA A,slow. Slow sIPSCs occur infrequently, suggesting that the cells underlying these events have a low spontaneous firing rate, unlike the cells giving rise to fast sIPSCs. Like evoked GABA A,fast and GABA A,slow, fast and slow sIPSCs are modulated differentially by furosemide, a subtype-specific GABA A antagonist. Furosemide blocks fast IPSCs by acting directly on the postsynaptic receptors, because it reduces the amplitude of both miniature IPSCs and the responses of excised patches to applied GABA. Thus, in the hippocampus, parallel inhibitory circuits are composed of separate populations of interneurons that contact anatomically segregated and pharmacologically distinct postsynaptic receptors.