Circuit and molecular architecture of a ventral hippocampal network

The ventral hippocampus (vHPC) is a critical hub in networks that process emotional information. While recent studies have indicated that vHPC projection neurons are functionally dissociable, the basic principles of how the inputs and outputs of the vHPC are organized remain unclear. Here we used viral and sequencing approaches to define the logic of the extended vHPC circuit. Through molecular profiling of vHPC projection neurons, we show that vHPC neurons with distinct projection targets differ in their transcriptional signatures. In this study we determined whether ventral hippocampal (vHPC) neurons that project to one of four target areas, lateral hypothalamus (LH) basomedial amygdala (BMA), medial prefrontal cortex (mPFC), and nucleus accumbens (NAc), differ in terms of the genes they express. To do so, we used transcriptional profiling methods that accessed translating mRNAs in ventral hippocampal neurons defined by their projection to one of these four targets. We labeled ventral hippocampal neurons that projected to ateral hypothalamus (LH) basomedial amygdala (BMA), medial prefrontal cortex (mPFC), and nucleus accumbens (NAc), in different cohorts of B6.129S4-Gt(ROSA)26Sortm1(CAG-EGFP/Rpl10a,-birA)Wtp/J (Jackson labs stock #022367) by injection of a retrograde traveling adenoassociated virus expressing Cre recombinase in each of the target areas, then used a translating ribosome affinity purification (TRAP) approach to profile translation in each of these populations . RNA sequencing (RNAseq) was then performed to identify differentially enriched mRNAs in the distinct vHPC projection neurons . Each sample correspond to 6 hippocampi from each projection pathway, perfomed in duplicate or triplicate.