Rapid and reversible chemical inactivation of synaptic transmission in genetically targeted neurons

Karpova, A. Y., Tervo, D. G., Gray, N. W., Svoboda, K. (December 2005) Rapid and reversible chemical inactivation of synaptic transmission in genetically targeted neurons. Neuron, 48 (5). pp. 727-35. ISSN 0896-6273 (Print)

URL: http://www.ncbi.nlm.nih.gov/pubmed/16337911
DOI: 10.1016/j.neuron.2005.11.015

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.

Item Type: Paper
Uncontrolled Keywords: Molecules for Inactivation of Synaptic Transmission MISTs modified presynaptic proteins inteference
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene silencing
organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > synaptic transmission
CSHL Authors:
Communities: CSHL labs > Svoboda lab
Watson School > Publications
Depositing User: CSHL Librarian
Date: 8 December 2005
Date Deposited: 10 Jan 2012 19:23
Last Modified: 19 Sep 2014 15:45
Related URLs:
URI: http://repository.cshl.edu/id/eprint/22616

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