Gene-targeted, CREB-mediated induction of ?FosB controls distinct downstream transcriptional patterns within D1 and D2 medium spiny neurons

?FosB, a transcription factor that accumulates in nucleus accumbens (NAc) after exposure to virtually every known rewarding substance, has been shown to directly control gene transcription and behavior downstream of both cocaine and opioid exposure but with potentially different roles in D1 and D2 medium spiny neurons (MSNs). To clarify MSN subtype-specific roles for ?FosB, and investigate how these subtypes coordinate the actions of distinct classes of addictive drugs, we developed a CRISPR/Cas9-based epigenome editing tool to induce endogenous ?FosB expression in vivo in the absence of drug exposure and performed RNA-sequencing on bulk male and female NAc tissue. Overall design: Transcriptional patterns in male and female mouse nucleus accumbens after activating the transcription factor ?FosB in D1, D2, or D1+D2 medium spiny neurons