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Clinical Implications of Basic Neuroscience Research | Circuits and Circuit Disorders

Chemogenetics—A Transformational and Translational Platform

Justin G. English, PhD1; Bryan L. Roth, MD, PhD1
[+] Author Affiliations
1Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill
JAMA Neurol. 2015;72(11):1361-1366. doi:10.1001/jamaneurol.2015.1921.
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Neurologic disorders are frequently a result of inappropriate electrical and/or chemical signaling of neurons and glia. Ultimate remediation would necessitate reprogramming these signals. Historically, correcting neuronal and glial signaling is accomplished via drug therapy/administration, although they frequently fail to effectively and fully treat the underlying disorder. Developments in basic research have produced several new classes of potential therapeutics to directly and precisely control neuron activity at the single-cell level. We review one such technology, Designer Receptors Exclusively Activated by Designer Drugs, and suggest its potential as a powerful tool for augmenting neuronal and glial signaling and activity for basic and translational applications.

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Figure 1.
Annual Rate of Designer Receptors Exclusively Activated by Designer Drug (DREADD) Publications
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Figure 2.
The Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) System

AAV indicates adeno-associated virus; CamKIIα, calmodulin-dependent protein kinase IIα; cAMP, cyclic adenosine monophosphate; CNO, clozapine-N-oxide; DIO, double-floxed inverted open reading frame; GsD, Gαs-coupled DREADD; hM3Dq, Gαq-coupled DREADD; hM4Di, Gαi-coupled DREADD; hSyn, human synapsin; iPS, induced pluripotent stem; KORD, DREADD based on the κ opioid receptor; PVH, paraventricular nucleus of hypothalamus; Rq(R165L), hM3Dq Gαq-coupled DREADD with the R165L mutation; and SalB, salvinorin A metabolite salvinorin B. Brown mouse image by George Shuklin (CC BY-SA 1.0; Wikimedia Commons [http://creativecommons.org/licenses/by-sa/1.0]). Feeding mouse image by Rama (CC BY-SA 2.0 fr; Wikimedia Commons [http://creativecommons.org/licenses/by-sa/2.0/fr/deed.en]). Hood rat photograph by Jason Snyder (CC BY 2.0; Wikimedia Commons [http://creativecommons.org/licenses/by/2.0]).

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