Rabies screen reveals GPe control of cocaine-triggered plasticity

Kevin T. Beier, Christina K. Kim, Paul Hoerbelt, Lin Wai Hung, Boris D. Heifets, Katherine E. DeLoach, Timothy J. Mosca, Sophie Neuner, Karl Deisseroth, Liqun Luo () and Robert C. Malenka ()
Additional contact information
Kevin T. Beier: Nancy Pritzker Laboratory, Stanford University School of Medicine
Christina K. Kim: Neurosciences Program, Stanford University
Paul Hoerbelt: Nancy Pritzker Laboratory, Stanford University School of Medicine
Lin Wai Hung: Nancy Pritzker Laboratory, Stanford University School of Medicine
Boris D. Heifets: Nancy Pritzker Laboratory, Stanford University School of Medicine
Katherine E. DeLoach: Stanford University
Timothy J. Mosca: Stanford University
Sophie Neuner: Nancy Pritzker Laboratory, Stanford University School of Medicine
Karl Deisseroth: Stanford University
Liqun Luo: Stanford University
Robert C. Malenka: Nancy Pritzker Laboratory, Stanford University School of Medicine

Nature, 2017, vol. 549, issue 7672, 345-350

Abstract: Abstract Identification of neural circuit changes that contribute to behavioural plasticity has routinely been conducted on candidate circuits that were preselected on the basis of previous results. Here we present an unbiased method for identifying experience-triggered circuit-level changes in neuronal ensembles in mice. Using rabies virus monosynaptic tracing, we mapped cocaine-induced global changes in inputs onto neurons in the ventral tegmental area. Cocaine increased rabies-labelled inputs from the globus pallidus externus (GPe), a basal ganglia nucleus not previously known to participate in behavioural plasticity triggered by drugs of abuse. We demonstrated that cocaine increased GPe neuron activity, which accounted for the increase in GPe labelling. Inhibition of GPe activity revealed that it contributes to two forms of cocaine-triggered behavioural plasticity, at least in part by disinhibiting dopamine neurons in the ventral tegmental area. These results suggest that rabies-based unbiased screening of changes in input populations can identify previously unappreciated circuit elements that critically support behavioural adaptations.

Date: 2017
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DOI: 10.1038/nature23888

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