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Front Mol Neurosci. 2016 Aug 30;9:75. doi: 10.3389/fnmol.2016.00075. eCollection 2016.

Causal Interrogation of Neuronal Networks and Behavior through Virally Transduced Ivermectin Receptors.

Author information

1
Sprengel Research Group, Department of Molecular Neurobiology, Max Planck Institute for Medical Research Heidelberg, Germany.
2
OpenLab of Neurobiology, Kazan Federal UniversityKazan, Russia; Division of Neuro- and Sensory Physiology, Institute of Physiology and Pathophysiology, Heidelberg UniversityHeidelberg, Germany.
3
Department of Medical Cell Biology, Institute for Anatomy and Cell Biology, Heidelberg University Heidelberg, Germany.
4
Department of Molecular Neurobiology, Max Planck Institute for Medical Research Heidelberg, Germany.
5
Sprengel Research Group, Department of Molecular Neurobiology, Max Planck Institute for Medical ResearchHeidelberg, Germany; Department of Medical Cell Biology, Institute for Anatomy and Cell Biology, Heidelberg UniversityHeidelberg, Germany.

Abstract

The causal interrogation of neuronal networks involved in specific behaviors requires the spatially and temporally controlled modulation of neuronal activity. For long-term manipulation of neuronal activity, chemogenetic tools provide a reasonable alternative to short-term optogenetic approaches. Here we show that virus mediated gene transfer of the ivermectin (IVM) activated glycine receptor mutant GlyRα1 (AG) can be used for the selective and reversible silencing of specific neuronal networks in mice. In the striatum, dorsal hippocampus, and olfactory bulb, GlyRα1 (AG) promoted IVM dependent effects in representative behavioral assays. Moreover, GlyRα1 (AG) mediated silencing had a strong and reversible impact on neuronal ensemble activity and c-Fos activation in the olfactory bulb. Together our results demonstrate that long-term, reversible and re-inducible neuronal silencing via GlyRα1 (AG) is a promising tool for the interrogation of network mechanisms underlying the control of behavior and memory formation.

KEYWORDS:

glycine receptor; ivermectin; neuronal silencing; odor discrimination; rAAV

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