Discrete hippocampal projections are differentially regulated by parvalbumin and somatostatin interneurons

People with schizophrenia show hyperactivity in the ventral hippocampus (vHipp) and we have previously demonstrated distinct behavioral roles for vHipp cell populations. Here, we test the hypothesis that parvalbumin (PV) and somatostatin (SST) interneurons differentially innervate and regulate hippocampal pyramidal neurons based on their projection target. First, we use eGRASP to show that PV-positive interneurons form a similar number of synaptic connections with pyramidal cells regardless of their projection target while SST-positive interneurons preferentially target nucleus accumbens (NAc) projections. To determine if these anatomical differences result in functional changes, we used in vivo opto-electrophysiology to show that SST cells also preferentially regulate the activity of NAc-projecting cells. These results suggest vHipp interneurons differentially regulate that vHipp neurons that project to the medial prefrontal cortex (mPFC) and NAc. Characterization of these cell populations may provide potential molecular targets for the treatment schizophrenia and other psychiatric disorders associated with vHipp dysfunction. Retrograde virus was used to fluorescently label vHipp neurons that project to the mPFC or NAc in C57BL/6 mice. Six weeks after viral injection, flow cytometry was used to sort out fluorescently labeled cells. RNASeq was used to determine the transcriptional profile of mPFC- or NAc-projecting pyramidal cells from 5-6 animals per group.