5-HT7 receptors medulate GABAergic transmission in the CA1 area of rat hippocampus
Hippocampal GABAergic interneurons modulate the activity of principal glutamatergic cells. Hippocampus receives 5-HT innervation originating in raphe nuclei. In this study we aimed at establishing whether the 5-HT7 receptor-dependent modulation of hippocampal functions also involves local inhibitory circuits. We investigated the effects of 5-HT7 receptor activation on the glutamatergic input to stratum lacunosum moleculare GABAergic interneurons and on the GABAergic input to pyramidal cells of the CA1 area. The experiments were performed on hippocampal slices using whole-cell patch-clamp technique. Neurons were visualized and identified by the shape of the soma as well as by the spiking pattern. For the recording of sIPSCs neurons were voltage clamped at 0 mV and sEPSCs were recorded at -76 mV. The amplitude and the frequency of sIPSCs recorded from pyramidal neurons as well as the amplitude and the frequency of sEPSCs recorded from GABA interneurons were measured. To activate the 5-HT7 receptor, 5-CT (a nonselective 5-HT7 receptor agonist) was applied in the presence of WAY 100635 (the 5-HT1A receptor antagonist). The application of 5-CT increased the mean frequency of sIPSCs and sEPSCs while the mean amplitudes of sIPSCS and sEPSCs were not altered. In the presence of a nonselective glutamate receptor antagonist, kynurenic acid, 5-CTmediated increase in the sIPSCs frequency was still present. These data suggest that the activation of the 5-HT7 receptor results in an enhancement of the GABAergic transmission via two mechanisms. The first one is an enhancement of excitatory glutamatergic input to GABAergic interneurons and the second - an increase of the excitability of GABAergic cells and /or an increase of GABA release due the activation of 5-HT7 receptors located in the perisomatic region of GABAergic cells and/or on GABAergic terminals. Support: MNiSW grant 0259/B/P01/2010/38.
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