Inert designer ligand-receptor for genetically targeted activation

Recently, Alexander et al. published Remote Control of Neuronal Activity in Transgenic Mice Expressing Evolved G Protein-Coupled Receptors [Neuron Neurotechniques], in which they use directed evolution techniques to modify a muscarinic GPCR to selectively bind an orally-deliverable small molecule that is otherwise inert. Apparently, this is the first time a channel has been engineered such that is selective for a biologically inert molecule, providing specificity of action. (They compare their technology with the hyperpolarizing allatostatin receptor which can have off-target effects.) Because the channel is specified genetically and the drug circulates systemically, it is easier to activate large populations of neurons (viz. optogenetic methods which are constrained to neurons in the light delivery volume) without implanted devices (eg. cannulas for AlstR, fiber optics for optogenetics, etc.) Another new technique/neurotechnology… onwards marches the innovation of new circuit-cracking tools!

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