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Cell Press, Neuron, 5(48), p. 727-735, 2005

DOI: 10.1016/j.neuron.2005.11.015

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Rapid and Reversible Chemical Inactivation of Synaptic Transmission in Genetically Targeted Neurons

Journal article published in 2005 by Alla Y. Karpova, Dougal G. R. Tervo, Noah W. Gray ORCID, Karel Svoboda
Distributing this paper is prohibited by the publisher
Distributing this paper is prohibited by the publisher

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Abstract

Inducible and reversible silencing of selected neurons in vivo is critical to understanding the structure and dynamics of brain circuits. We have developed Molecules for Inactivation of Synaptic Transmission (MISTs) that can be genetically targeted to allow the reversible inactivation of neurotransmitter release. MISTs consist of modified presynaptic proteins that interfere with the synaptic vesicle cycle when crosslinked by small molecule "dimerizers." MISTs based on the vesicle proteins VAMP2/Synaptobrevin and Synaptophysin induced rapid ( approximately 10 min) and reversible block of synaptic transmission in cultured neurons and brain slices. In transgenic mice expressing MISTs selectively in Purkinje neurons, administration of dimerizer reduced learning and performance of the rotarod behavior. MISTs allow for specific, inducible, and reversible lesions in neuronal circuits and may provide treatment of disorders associated with neuronal hyperactivity.