Generation and Characterization of a Novel Prkcd-Cre Rat Model

Activity of central amygdala (CeA) PKCS expressing neurons has been linked to appetite regulation, anxiety-like behaviors, pain sensitivity, and addiction-related behaviors. Studies of the role that CeA PKCS+ neurons play in these behaviors have largely been carried out in mice, and genetic tools that would allow selective manipulation of PKCS+ cells in rats have been lacking. Here, we used a CRISPR/Cas9 strategy to generate a transgenic Prkcd-cre knock-in rat and characterized this model using anatomical, electrophysiological, and behavioral approaches in both sexes. In the CeA, Cre was selectively expressed in PKCS+ cells. Anterograde projections of PKCS+ neurons to cortical regions, subcortical regions, several hypothalamic nuclei, the amygdala complex, and midbrain dopaminergic regions were largely consistent with published mouse data. In a behavioral screen, we found no differences between Cre+ rats and Cre- wild-type littermates. Optogenetic stimulation of CeA PKCS+ neurons in a palatable food intake assay resulted in an increased latency to first feeding and decreased total food intake, once again replicating published mouse findings. Lastly, using a real-time place preference task, we found that stimulation of PKCS+ neurons promoted aversion, without affecting locomotor activity. Collectively, these findings establish the novel Prkcd-Cre rat line as a valuable tool that complements available mouse lines for investigating the functional role of PKCS+ neurons.