Dataset Information

A Subset of Nucleus Accumbens Neurons Receiving Dense and Functional Prelimbic Cortical Input Are Required for Cocaine Seeking.

ABSTRACT:

Background

Prelimbic cortical projections to the nucleus accumbens core are critical for cue-induced cocaine seeking, but the identity of the accumbens neuron(s) targeted by this projection, and the transient neuroadaptations contributing to relapse within these cells, remain unknown.

Methods

Male Sprague-Dawley rats underwent cocaine or sucrose self-administration, extinction, and cue-induced reinstatement. Pathway-specific chemogenetics, patch-clamp electrophysiology, in vivo electrochemistry, and high-resolution confocal microscopy were used to identify and characterize a small population of nucleus accumbens core neurons that receive dense prelimbic cortical input to determine their role in regulating cue-induced cocaine and natural reward seeking.

Results

Chemogenetic inhibition of prelimbic cortical projections to the nucleus accumbens core suppressed cue-induced cocaine relapse and normalized real-time cue-evoked increases in accumbens glutamate release to that of sucrose seeking animals. Furthermore, chemogenetic inhibition of the population of nucleus accumbens core neurons receiving the densest prelimbic cortical input suppressed cocaine, but not sucrose seeking. These neurons also underwent morphological plasticity during the peak of cocaine seeking in the form of dendritic spine expansion and increased ensheathment by astroglial processes at large spines.

Conclusion

We identified and characterized a unique subpopulation of nucleus accumbens neurons that receive dense prelimbic cortical input. The functional specificity of this subpopulation is underscored by their ability to mediate cue-induced cocaine relapse, but not sucrose seeking. This subset of cells represents a novel target for addiction therapeutics revealed by anterograde targeting to interrogate functional circuits imbedded within a known network.

SUBMITTER: Siemsen BM

PROVIDER: S-EPMC8907444 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

A Subset of Nucleus Accumbens Neurons Receiving Dense and Functional Prelimbic Cortical Input Are Required for Cocaine Seeking.

Siemsen Benjamin M BM Barry Sarah M SM Vollmer Kelsey M KM Green Lisa M LM Brock Ashley G AG Westphal Annaka M AM King Raven A RA DeVries Derek M DM Otis James M JM Cowan Christopher W CW Scofield Michael D MD

Frontiers in cellular neuroscience 20220224

<h4>Background</h4>Prelimbic cortical projections to the nucleus accumbens core are critical for cue-induced cocaine seeking, but the identity of the accumbens neuron(s) targeted by this projection, and the transient neuroadaptations contributing to relapse within these cells, remain unknown.<h4>Methods</h4>Male Sprague-Dawley rats underwent cocaine or sucrose self-administration, extinction, and cue-induced reinstatement. Pathway-specific chemogenetics, patch-clamp electrophysiology, <i>in vivo ...[more]

PMID: 35281297

Similar Datasets

Project description:BackgroundSubstance use disorder is a neurobiological disease characterized by episodes of relapse despite periods of withdrawal. It is thought that neuroadaptations in discrete brain areas of the reward pathway, including the nucleus accumbens, underlie these aberrant behaviors. The ubiquitin-proteasome system degrades proteins and has been shown to be involved in cocaine-induced plasticity, but the role of E3 ubiquitin ligases, which conjugate ubiquitin to substrates, is unknown. Here, we examined E3 ubiquitin-protein ligase SMURF1 (SMURF1) in neuroadaptations and relapse behavior during withdrawal following cocaine self-administration.MethodsSMURF1 and downstream targets ras homolog gene family, member A (RhoA), SMAD1/5, and Runt-related transcript factor 2 were examined using Western blotting (n = 9-11/group), quantitative polymerase chain reaction (n = 6-9/group), co-immunoprecipitation (n = 9-11/group), tandem ubiquitin binding entities affinity purification (n = 5-6/group), and quantitative chromatin immunoprecipitation (n = 3-6/group) (2 rats/sample). Viral-mediated gene transfer (n = 7-12/group) and intra-accumbal microinjections (n = 9-10/group) were used to examine causal roles of SMURF1 and substrate RhoA, respectively, in cue-induced cocaine seeking.ResultsSMURF1 protein expression was decreased, while SMURF1 substrates RhoA and SMAD1/5 were increased, in the nucleus accumbens on withdrawal day 7, but not on withdrawal day 1, following cocaine self-administration. Viral-mediated gene transfer of Smurf1 or constitutive activation of RhoA attenuated cue-induced cocaine seeking, while catalytically inactive Smurf1 enhanced cocaine seeking. Furthermore, SMURF1-regulated, SMAD1/5-associated transcription factor Runt-related transcript factor 2 displayed increased binding at promoter regions of genes previously associated with cocaine-induced plasticity.ConclusionsSMURF1 is a key mediator of neuroadaptations in the nucleus accumbens following cocaine exposure and mediates cue-induced cocaine seeking during withdrawal.

Dataset Information

A Subset of Nucleus Accumbens Neurons Receiving Dense and Functional Prelimbic Cortical Input Are Required for Cocaine Seeking.

Background

Methods

Results

Conclusion

Publications

A Subset of Nucleus Accumbens Neurons Receiving Dense and Functional Prelimbic Cortical Input Are Required for Cocaine Seeking.

Similar Datasets

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