1. Transcriptional and physiological adaptations in nucleus accumbens somatostatin interneurons that regulate behavioral responses to cocaine.
- Author
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Ribeiro EA, Salery M, Scarpa JR, Calipari ES, Hamilton PJ, Ku SM, Kronman H, Purushothaman I, Juarez B, Heshmati M, Doyle M, Lardner C, Burek D, Strat A, Pirpinias S, Mouzon E, Han MH, Neve RL, Bagot RC, Kasarskis A, Koo JW, and Nestler EJ
- Subjects
- Animals, Brain metabolism, Gene Expression Profiling, Gene Expression Regulation drug effects, Gene Transfer Techniques, Locomotion, Male, Mice, Mice, Inbred C57BL, Neurons drug effects, Neurons metabolism, Optogenetics methods, Proto-Oncogene Proteins c-jun genetics, Proto-Oncogene Proteins c-jun metabolism, Reward, Sequence Analysis, RNA, Somatostatin pharmacology, Transcription Factors drug effects, Adaptation, Physiological drug effects, Cocaine pharmacology, Interneurons drug effects, Interneurons metabolism, Nucleus Accumbens drug effects, Nucleus Accumbens metabolism, Somatostatin metabolism, Transcriptome
- Abstract
The role of somatostatin interneurons in nucleus accumbens (NAc), a key brain reward region, remains poorly understood due to the fact that these cells account for < 1% of NAc neurons. Here, we use optogenetics, electrophysiology, and RNA-sequencing to characterize the transcriptome and functioning of NAc somatostatin interneurons after repeated exposure to cocaine. We find that the activity of somatostatin interneurons regulates behavioral responses to cocaine, with repeated cocaine reducing the excitability of these neurons. Repeated cocaine also induces transcriptome-wide changes in gene expression within NAc somatostatin interneurons. We identify the JUND transcription factor as a key regulator of cocaine action and confirmed, by use of viral-mediated gene transfer, that JUND activity in somatostatin interneurons influences behavioral responses to cocaine. Our results identify alterations in NAc induced by cocaine in a sparse population of somatostatin interneurons, and illustrate the value of studying brain diseases using cell type-specific whole transcriptome RNA-sequencing.
- Published
- 2018
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