Chemogenetics

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Chemogenetics

Chemogenetics combines chemical reactions with genetic engineering to control the physiological activities of cells. The most widely used molecules include G protein-coupled receptors (GPCR) and ligand-gated ion channels, which are engineered so that they respond to specific small molecules rather than their endogenous ligands. Because of its controllable and reversible (compounds can be added or removed at any time to start or interrupt specific reactions) features, it has been widely used in the research of neural signal transduction.

Principle Chemogenetics uses synthetically derived receptors and selective ligands for transient activation or inactivation of targeted brain areas (Designer Receptors Exclusively Activated by Designer Drugs, DREADDs). DREADD receptors are engineered from G protein-coupled receptors which are relatively insensitive to endogenous ligands, but can be activated by clozapine-N-oxide (CNO), which in turn triggers the G protein signaling cascade and leads to various physiological changes.

Fig.5 DREADDs are used to activate and inhibit groups of neurons.

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Chemogenetics


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