Dataset Information

Complementary Genetic Targeting and Monosynaptic Input Mapping Reveal Recruitment and Refinement of Distributed Corticostriatal Ensembles by Cocaine.

ABSTRACT: Drugs of abuse elicit powerful experiences that engage populations of neurons broadly distributed throughout the brain. To determine how synaptic connectivity is organized to enable robust communication between populations of drug-activated neurons, we developed a complementary targeting system for monosynaptic rabies virus (RV) tracing that identifies direct inputs to activated versus nonactivated neuronal populations. Analysis of over 100,000 synaptic input neurons demonstrated that cocaine-activated neurons comprise selectively connected but broadly distributed corticostriatal networks. Electrophysiological assays using optogenetics to stimulate activated versus nonactivated inputs revealed stronger synapses between coactivated cortical pyramidal neurons and neurons in the dorsal striatum (DS). Repeated cocaine exposure further enhanced the connectivity specifically between drug-activated neurons in the orbitofrontal cortex (OFC) and coactive DS neurons. Selective chemogenetic silencing of cocaine-activated OFC neurons or their terminals in the DS disrupted behavioral sensitization, demonstrating the utility of this methodology for identifying novel circuit elements that contribute to behavioral plasticity.

SUBMITTER: Wall NR

PROVIDER: S-EPMC6941653 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Publications

Complementary Genetic Targeting and Monosynaptic Input Mapping Reveal Recruitment and Refinement of Distributed Corticostriatal Ensembles by Cocaine.

Wall Nicholas R NR Neumann Peter A PA Beier Kevin T KT Mokhtari Ava K AK Luo Liqun L Malenka Robert C RC

Neuron 20191120 5

Drugs of abuse elicit powerful experiences that engage populations of neurons broadly distributed throughout the brain. To determine how synaptic connectivity is organized to enable robust communication between populations of drug-activated neurons, we developed a complementary targeting system for monosynaptic rabies virus (RV) tracing that identifies direct inputs to activated versus nonactivated neuronal populations. Analysis of over 100,000 synaptic input neurons demonstrated that cocaine-ac ...[more]

PMID: 31759807

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Dataset Information

Complementary Genetic Targeting and Monosynaptic Input Mapping Reveal Recruitment and Refinement of Distributed Corticostriatal Ensembles by Cocaine.

Publications

Complementary Genetic Targeting and Monosynaptic Input Mapping Reveal Recruitment and Refinement of Distributed Corticostriatal Ensembles by Cocaine.

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