Physiological evidence for hippocampal disinhibition resulting from activation of the median raphe

The mechanism underlying median raphe (MR)-induced facilitation of hippocampal synaptic transmission was investigated by recording stimulus-evoked field potentials and unitary responses in urethane-anesthetized rats. Stimulation of the MR 40 ms prior to perforant path (PP) activation significantly increased the magnitude of PP-evoked granule cell population spikes (median increase = 78%) without affecting population EPSP slope. Injection of homocysteic acid into the vicinity of the MR also facilitated PP-evoked granule cell population spikes, in a dose-dependent manner. Nineteen dentate hilar units were characterized as putative interneurons on the basis of their waveform characteristics and their response to PP stimulation. Electrical activation of the MR inhibited spontaneous or PP-evoked activity in the majority (75%) of these cells; the remaining cells were unaffected. MR stimulation also inhibited spontaneous activity in a large proportion (60%) of putative interneurons in CA1. The present results provide evidence that neurons within the raphe modulate hippocampal throughput by altering discharge of non-principal cells. These data, thus, support the idea that disinhibition is a common mechanism by which extrahippocampal structures modulate information flow through the hippocampus.