Cell-type-specific modulation of feedback inhibition by serotonin in the hippocampus

Midbrain raphe nuclei provide strong serotonergic projections tothe hippocampus, in which serotonin (5-HT) exerts differential effects mediatedby multiple 5-HT receptor subtypes. The functional relevance of this diversity of information processingis poorly understood. Here we show that serotonin via 5-HT_1B heteroreceptors substantially reduces synaptic excitation of cholecystokinin-expressing in-terneurons in area CA1 of the rat hippocampus, in contrast to parvalbumin-expressing basket cells. The reduction is input specific, affecting only glutamatergic synaptic transmission originating from CA1 pyramidal cells. As a result, serotonin selectively decreases feedback inhibition via 5-HT_1B receptor activation and subsequently increases the integration time window for spike generation in CA1 pyramidalcells.Ourdataimplyanimportantrolefor serotonergicmodulationofGABAergic actioninsubcorticalcontrolofhippocampal output.