Hippocampal pyramidal cells express several alpha-subunits, which determine the affinity of GABAA (gamma-aminobutyric acid) receptors for benzodiazepine site ligands. This study asked whether inhibitory postsynaptic potentials (IPSPs) elicited by specific interneuronal subclasses were differentially sensitive to the alpha1-preferring agonist Zolpidem, i.e. whether different receptors mediate different inhibitory connections. Paired intracellular recordings in which the presynaptic cell was an interneuron and the postsynaptic cell a CA1 pyramid were performed in slices of adult rat hippocampus. Resultant IPSPs were challenged with Zolpidem, cells filled with biocytin and identified morphologically. IPSPs elicited by fast spiking (FS) basket cells (n = 9) were enhanced more than IPSPs elicited by regular spiking (RS) basket cells (n = 10). At FS basket cell synapses the efficacy of Zolpidem was equivalent to that of Diazepam, while RS basket cell IPSPs are enhanced 50% less by Zolpidem than by Diazepam. Thus, while alpha1 subunits may dominate at synapses supplied by FS basket cells, RS basket cell synapses also involve alpha2/3 subunits. Two bistratified cell IPSPs tested with Zolpidem did not increase in amplitude, despite powerful enhancements of bistratified cell IPSPs by Diazepam, consistent with previous indications that these synapses utilize alpha5-containing receptors. Enhancements of basket cell IPSPs by Zolpidem and Diazepam were bi- or triphasic with steep amplitude increases separated by plateaux, occurring 10-15, 25-30 and 45-55 min after adding the drug to the bath. The entire enhancement was, however, blocked by the antagonist Flumazenil (n = 7). Flumazenil, either alone (n = 3), or after Zolpidem, reduced IPSP amplitude to approximately 90% of control, suggesting that alpha4-containing receptors were not involved.

Simultaneous intracellular recordings from presynaptic Stratum pyramidale interneurons and postsynaptic pyramidal cells in adult rat hippocampal slices were performed to investigate the strength of the modulation of single-axon inhibitory postsynaptic potentials (IPSPs) by the GABAA receptor modulators pentobarbitone, diazepam and zinc. The processing of biocytin-filled interneurons for light microscopy revealed that these single-axon IPSPs were generated by basket cells (n = 33), bistratified cells (n = 18) and axo-axonic cells (n = 2). The IPSPs generated by these three groups of interneurons had amplitudes and widths at half amplitude with similar ranges, but when bistratified cell IPSPs were compared with basket cell IPSPs with similar half widths their rise times were slower. Pentobarbitone sodium (250 microM) powerfully enhanced 13 tested IPSPs generated by all three cell types. Amplitudes were enhanced by 82 +/- 56%, 10-90% rise times by 150 +/- 101% and the widths at half amplitude by 71 +/- 29%. Diazepam (1-2 microM) also increased all IPSPs tested, although the changes were more moderate in basket cell IPSPs (amplitudes increased by 19 +/- 11%, n = 8) than in bistratified cell IPSPs (amplitudes increased by 66 +/- 48%, n = 5). Basket cell IPSP 10-90% rise times and widths at half amplitude were not significantly increased. Bistratified cell IPSP 10-90% rise times were increased by 44 +/- 24% and the widths at half amplitude by 32 +/- 35%. The one tested IPSP generated by an axo-axonic cell was also diazepam-sensitive. Zinc, 250 microM, decreased four out of 10 IPSPs generated by basket cells and four out of five IPSPs generated by bistratified cells. The one tested axo-axonic cell IPSP was zinc-insensitive. These data suggest that IPSPs generated in CA1 pyramidal cells by basket and bistratified cells display different pharmacologies and may be mediated by different receptors or receptor combinations.

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