Differential genetic expression within reward-specific ensembles in mice

Maladaptive reward seeking is a hallmark of cocaine use disorder. To develop therapeutic targets, it is critical to understand the neurobiological changes specific to cocaine-seeking without altering the seeking of natural rewards, e.g., sucrose. The prefrontal cortex (PFC) and the nucleus accumbens core (NAcore) are known regions associated with cocaine- and sucrose-seeking ensembles, i.e., a sparse population of co-activated neurons. Within ensembles, transcriptomic alterations in the PFC and NAcore underlie the learning and persistence of cocaine- and sucrose-seeking behavior. However, transcriptomes exclusively driving cocaine seeking independent from sucrose seeking have not yet been defined using a within-subject approach. Using Ai14:cFos-TRAP2 transgenic mice in a dual cocaine and sucrose self-administration model, we fluorescently sorted (FACS) and characterized (RNAseq) the transcriptomes defining cocaine- and sucrose-seeking ensembles. We found reward- and region-specific transcriptomic changes that will help develop clinically relevant genetic approaches to decrease cocaine-seeking behavior without altering non-drug reward-based positive reinforcement. The 60 RNA-sequencing fastq sample files are labeled in the sequential order: sex (male = M; female = F), region (nucleus accumbens core = N; prefrontal cortex = P), replicate (replicate 1 = 1; replicate 2 = 2; replicate 3 = 3), and cell population type (cocaine-seeking ensemble = C; sucrose-seeking ensemble = S; overlapping ensemble = O; non-ensemble = NonEns; naive = Naive). Naive samples were used downstream for reference compared to other cell population types. Supplemental files for each sample are unnormalized and unfiltered transcript count output from Salmon.