Generation and Characterization of a Novel Prkcd- Cre Rat Model.

Autor:	Toivainen S; Department of Clinical and Experimental Medicine, Linkoping University, Linkoping 58225, Sweden., Petrella M; Department of Clinical and Experimental Medicine, Linkoping University, Linkoping 58225, Sweden., Xu L; Department of Clinical and Experimental Medicine, Linkoping University, Linkoping 58225, Sweden., Visser E; Department of Clinical and Experimental Medicine, Linkoping University, Linkoping 58225, Sweden., Weiss T; Department of Clinical and Experimental Medicine, Linkoping University, Linkoping 58225, Sweden., Vellere S; School of Pharmacy, Center for Neuroscience, Pharmacology Unit, University of Camerino, Camerino 62032, Italy., Zeier Z; Department of Psychiatry and Behavioral Sciences, Center for Therapeutic Innovation, University of Miami Miller School of Medicine, Miami, Florida 33136., Wahlestedt C; Department of Psychiatry and Behavioral Sciences, Center for Therapeutic Innovation, University of Miami Miller School of Medicine, Miami, Florida 33136., Barbier E; Department of Clinical and Experimental Medicine, Linkoping University, Linkoping 58225, Sweden., Domi E; Department of Clinical and Experimental Medicine, Linkoping University, Linkoping 58225, Sweden.; School of Pharmacy, Center for Neuroscience, Pharmacology Unit, University of Camerino, Camerino 62032, Italy., Heilig M; Department of Clinical and Experimental Medicine, Linkoping University, Linkoping 58225, Sweden markus.heilig@liu.se.
Jazyk:	angličtina
Zdroj:	The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2024 Aug 07; Vol. 44 (32). Date of Electronic Publication: 2024 Aug 07.
DOI:	10.1523/JNEUROSCI.0528-24.2024
Abstrakt:	Activity of central amygdala (CeA) PKCδ expressing neurons has been linked to appetite regulation, anxiety-like behaviors, pain sensitivity, and addiction-related behaviors. Studies of the role that CeA PKCδ+ neurons play in these behaviors have largely been carried out in mice, and genetic tools that would allow selective manipulation of PKCδ+ 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 PKCδ+ cells. Anterograde projections of PKCδ+ 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 PKCδ+ 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 PKCδ+ 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 PKCδ+ neurons. Competing Interests: M.H. has received consulting fees, research support, or other compensation from Indivior, Camurus, BrainsWay, Aelis Farma, and Janssen Pharmaceuticals. The other authors declare no competing financial interests. (Copyright © 2024 Toivainen et al.)
Databáze:	MEDLINE
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