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Front Neural Circuits. 2019 Feb 1;13:4. doi: 10.3389/fncir.2019.00004. eCollection 2019.

Two eARCHT3.0 Lines for Optogenetic Silencing of Dopaminergic and Serotonergic Neurons.

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McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, United States.
Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard, Cambridge, MA, United States.
Institute of Cellular Physiology, Department of Neurodevelopment and Physiology, National Autonomous University of Mexico, Mexico City, Mexico.
Department of Bioengineering, Stanford University, Stanford, CA, United States.
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, United States.
Howard Hughes Medical Institute, Stanford University, Stanford, CA, United States.
Human Cell Types, Allen Institute for Brain Science, Seattle, WA, United States.


Dopaminergic and serotonergic neurons modulate and control processes ranging from reward signaling to regulation of motor outputs. Further, dysfunction of these neurons is involved in both degenerative and psychiatric disorders. Elucidating the roles of these neurons has been greatly facilitated by bacterial artificial chromosome (BAC) transgenic mouse lines expressing channelrhodopsin to readily enable cell-type specific activation. However, corresponding lines to silence these monoaminergic neurons have been lacking. We have generated two BAC transgenic mouse lines expressing the outward proton pump, enhanced ArchT3.0 (eArchT3.0), and GFP under control of the regulatory elements of either the dopamine transporter (DAT; Jax# 031663) or the tryptophan hydroxylase 2 (TPH2; Jax# 031662) gene locus. We demonstrate highly faithful and specific expression of these lines in dopaminergic and serotonergic neurons respectively. Additionally we validate effective and sensitive eArchT3.0-mediated silencing of these neurons using slice electrophysiology as well as with a well-established behavioral assay. These new transgenic tools will help expedite the study of dopaminergic and serotonergic system function in normal behavior and disease.


dopaminergic; eArchT3.0; inhibitory; mouse; opsin; serotonergic

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