FosB-regulated gene expression in venral hippocampo-accumbal projection neurons

We examined here the regulation of gene expression in ventral hippocampus neurons that project to nucleus accumbens (vHPC-NAc) by the transcription factor, ?FosB. The activity of this circuit is critical to stress-induced social withdrawal. ?FosB regulates the physiology and behavior of this circuit to produce resilience. Circuit-specific translating ribosomal affinity purification (TRAP) was conducted followed by RNASeq. A strain of floxed Fosb mice (the gene that encodes ?FosB) was crossed with a ribosomal L10-GFP fusion protein line (Rosa26). To target vHPC-NAc neurons, a retrograde recombinant HSV-Cre was injected into NAc to retrogradely drive expression of GFP and knockout the Fosb gene in vHPC-NAc. Bilateral biopsy punches of vHPC containing GFP-labeled projections were collected, pooled, and processed by TRAP followed by 3rd-generation sequencing of actively translating mRNA. We have now identified Fosb-regulated gene expression in a specific hippocampal-to-accumbens circuit that is important for resilience to stress-induced social withdrawal. Overall design: Circuit-specific mRNA profiles of ventral hippocampus projection neurons to NAc from wild type (WT) and FosB knockout (KO) mice were generated by deep sequencing, in triplicate.