The Synaptic Basis of GABA_A,slow

Abstract

Although two kinetically distinct evoked GABAA responses (GABAA,fast and GABAA,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 GABAA,fast in their rise and decay kinetics. The absence of slow sIPSCs calls into question the synaptic basis of GABAA,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 GABAA,fast and GABAA,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 GABAA,fast and GABAA,slow, fast and slow sIPSCs are modulated differentially by furosemide, a subtype-specific GABAA 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.

Theta-bursts induce a shift in reversal potentials for GABA-A receptor-mediated postsynaptic currents in rat hippocampal CA1 neurons

“…Furosemide, when tested on 3 control neurons (in which no theta-bursts were given) did not significantly changed the RP of the IPSC (before furosemide application: 63.17 ± 0.59 mV & after furosemide application: 61.92 ± 0.46 mV; P > 0.05). This observation is consistent with those of (Banks et al, 1998;Jarolimek et al, 1996;Jarolimek et al, 1999;Ouardouz and Sastry, 2005;Pearce, 1993).…”

“…Furosemide, when tested on 3 control neurons (in which no theta-bursts were given) did not significantly changed the RP of the IPSC (before furosemide application: 63.17 ± 0.59 mV & after furosemide application: 61.92 ± 0.46 mV; P > 0.05). This observation is consistent with those of (Banks et al, 1998;Jarolimek et al, 1996;Jarolimek et al, 1999;Ouardouz and Sastry, 2005;Pearce, 1993).Previous studies in our laboratory indicated that tetanic stimulations of inputs induce a shift in the RP for GABA-ergic PSCs of neonatal rat DCN neurons (Ouardouz and Sastry ., 2000;Ouardouz and Sastry., 2005) and neonatal rat hippocampal CA1 pyramidal neurons (Ouardouz et al, 2006). In DCN neurons, the tetanus-induced negative shift in the RP seems to be due to an increased expression and activation of KCC-2 through an activation of protein kinase A, protein synthesis and activation of protein phosphatases (Ouardouz and Sastry, 2005).…”

GABAergic synchronization in the limbic system and its role in the generation of epileptiform activity

“…It has been proposed that these interneurons may be involved in the generation of slow GABA A receptor-mediated potentials (Pearce, 1993;Freund and Buzsáki, 1996;Banks et al, 1998). In line with this view it has been recently reported that in the CA3 subfield inhibitory events generated at dendritic sites have similar amplitudes but occurred less frequently and had slower kinetics than perisomatic events generated in stratum pyramidale (Bazelot et al, 2010).…”

Computational model of carbachol‐induced delta, theta, and gamma oscillations in the hippocampus

“…These neurons were able to pace CA1 pyramidal cells at theta frequencies (Chap-man and Lacaille, 1999b). Two distinct GABA A IPSPs have been found, a fast one and slow one (Banks et al, 1998). The fast IPSP is important in gamma rhythms, whereas the slow IPSP has a time-scale similar to that of theta rhythms and could, therefore, be involved in theta oscillations (White et al, 2000).…”