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Nat Methods. 2016 Aug;13(8):673-8. doi: 10.1038/nmeth.3894. Epub 2016 Jun 6.

An E3-ligase-based method for ablating inhibitory synapses.

Author information

1
Department of Biology, Section of Molecular and Computational Biology, University of Southern California, Los Angeles, Los Angeles, California, USA.
2
Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, USA.
3
Centre de recherche, Institut universitaire en santé mentale de Québec, Québec, Québec, Canada.
4
Université Laval, Québec, Québec, Canada.
5
Department of Chemistry, University of Southern California, Los Angeles, Los Angeles, California, USA.

Abstract

Although neuronal activity can be modulated using a variety of techniques, there are currently few methods for controlling neuronal connectivity. We introduce a tool (GFE3) that mediates the fast, specific and reversible elimination of inhibitory synaptic inputs onto genetically determined neurons. GFE3 is a fusion between an E3 ligase, which mediates the ubiquitination and rapid degradation of proteins, and a recombinant, antibody-like protein (FingR) that binds to gephyrin. Expression of GFE3 leads to a strong and specific reduction of gephyrin in culture or in vivo and to a substantial decrease in phasic inhibition onto cells that express GFE3. By temporarily expressing GFE3 we showed that inhibitory synapses regrow following ablation. Thus, we have created a simple, reversible method for modulating inhibitory synaptic input onto genetically determined cells.

PMID:
27271196
PMCID:
PMC5312699
DOI:
10.1038/nmeth.3894
[Indexed for MEDLINE]
Free PMC Article

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