Generation and Characterization of a Novel Prkcd-Cre Rat Model

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This article discusses the generation of a novel Prkcd-Cre rat model to study the role of central amygdala (CeA) PKC expressing neurons in behaviors such as appetite regulation, anxiety, pain sensitivity, and addiction-related behaviors. The study used a CRISPR/Cas9 strategy to create the transgenic rat model and characterized it using anatomical, electrophysiological, and behavioral approaches. The model demonstrated selective expression of Cre in PKC+ cells in the CeA and exhibited consistent projections to various brain regions. Behavioral experiments showed no differences between Cre+ rats and wild-type littermates, but optogenetic stimulation of CeA PKC+ neurons resulted in altered food intake and aversion behaviors. Overall, the findings highlight the utility of the Prkcd-Cre rat model for studying PKC+ neuron function in comparison to existing mouse models.

Activity of central amygdala (CeA) PKC expressing neurons has been linked to appetite regulation, anxiety-like behaviors, pain sensitivity, and addiction-related behaviors. Studies of the role that CeA PKC+ neurons play in these behaviors have largely been carried out in mice, and genetic tools that would allow selective manipulation of PKC+ 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 PKC+ cells. Anterograde projections of PKC+ 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 PKC+ 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 PKC+ 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 PKC+ neurons.

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