Distinct Subpopulations of Nucleus Accumbens Dynorphin Neurons Drive Aversion and Reward

Ream Al-Hasani; Jordan G McCall; Gunchul Shin; Adrian M Gomez; Gavin P Schmitz; Julio M Bernardi; Chang-O Pyo; Sung Il Park; Catherine M Marcinkiewcz; Nicole A Crowley; Michael J Krashes; Bradford B Lowell; Thomas L Kash; John A Rogers; Michael R Bruchas

doi:10.1016/j.neuron.2015.08.019

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Distinct Subpopulations of Nucleus Accumbens Dynorphin Neurons Drive Aversion and Reward

Journal article

Open access

Peer reviewed

Distinct Subpopulations of Nucleus Accumbens Dynorphin Neurons Drive Aversion and Reward

Ream Al-Hasani, Jordan G McCall, Gunchul Shin, Adrian M Gomez, Gavin P Schmitz, Julio M Bernardi, Chang-O Pyo, Sung Il Park, Catherine M Marcinkiewcz, Nicole A Crowley, …

Neuron (Cambridge, Mass.), Vol.87(5), pp.1063-1077

09/02/2015

DOI: 10.1016/j.neuron.2015.08.019

PMCID: PMC4625385

PMID: 26335648

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Abstract

The nucleus accumbens (NAc) and the dynorphinergic system are widely implicated in motivated behaviors. Prior studies have shown that activation of the dynorphin-kappa opioid receptor (KOR) system leads to aversive, dysphoria-like behavior. However, the endogenous sources of dynorphin in these circuits remain unknown. We investigated whether dynorphinergic neuronal firing in the NAc is sufficient to induce aversive behaviors. We found that photostimulation of dynorphinergic cells in the ventral NAc shell elicits robust conditioned and real-time aversive behavior via KOR activation, and in contrast, photostimulation of dorsal NAc shell dynorphin cells induced a KOR-mediated place preference and was positively reinforcing. These results show previously unknown discrete subregions of dynorphin-containing cells in the NAc shell that selectively drive opposing behaviors. Understanding the discrete regional specificity by which NAc dynorphinerigic cells regulate preference and aversion provides insight into motivated behaviors that are dysregulated in stress, reward, and psychiatric disease.

Action Potentials - genetics

Electric Stimulation

Self Stimulation

Dynorphins - genetics

Male

Receptors, Dopamine D2 - metabolism

Neurons - classification

Time Factors

Nucleus Accumbens - cytology

Neurons - physiology

Dynorphins - metabolism

Protein Precursors - genetics

Mice, Inbred C57BL

Gene Expression Regulation

Mice, Transgenic

Avoidance Learning - physiology

Receptors, Dopamine D2 - genetics

Protein Precursors - metabolism

Animals

Maze Learning

Wireless Technology

Conditioning, Operant

Luminescent Proteins - genetics

Mice

Reward

In Vitro Techniques

Photic Stimulation

Luminescent Proteins - metabolism

Details

Title: Subtitle: Distinct Subpopulations of Nucleus Accumbens Dynorphin Neurons Drive Aversion and Reward
Creators: Ream Al-Hasani - Departments of Anesthesiology, Division of Basic Research, Anatomy and Neurobiology, Division of Biomedical Engineering and Washington University Pain Center, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: alhasanir@morpheus.wustl.edu
Jordan G McCall - Departments of Anesthesiology, Division of Basic Research, Anatomy and Neurobiology, Division of Biomedical Engineering and Washington University Pain Center, Washington University School of Medicine, Saint Louis, MO 63110, USA; Division of Biology and Biomedical Sciences, Washington University School of Medicine, Saint Louis, MO 63110, USA
Gunchul Shin - Department of Materials Science and Engineering, Frederick Seitz Materials Research Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
Adrian M Gomez - Departments of Anesthesiology, Division of Basic Research, Anatomy and Neurobiology, Division of Biomedical Engineering and Washington University Pain Center, Washington University School of Medicine, Saint Louis, MO 63110, USA
Gavin P Schmitz - Departments of Anesthesiology, Division of Basic Research, Anatomy and Neurobiology, Division of Biomedical Engineering and Washington University Pain Center, Washington University School of Medicine, Saint Louis, MO 63110, USA
Julio M Bernardi - Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO 63110, USA
Chang-O Pyo - Department of Electrical and Computer Engineering, Frederick Seitz Materials Research Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
Sung Il Park - Department of Materials Science and Engineering, Frederick Seitz Materials Research Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
Catherine M Marcinkiewcz - Department of Pharmacology and Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina, Chapel Hill, Chapel Hill, NC 27516, USA
Nicole A Crowley - Department of Pharmacology and Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina, Chapel Hill, Chapel Hill, NC 27516, USA
Michael J Krashes - Diabetes, Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA; National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA; Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
Bradford B Lowell - Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA
Thomas L Kash - Department of Pharmacology and Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina, Chapel Hill, Chapel Hill, NC 27516, USA
John A Rogers - Department of Materials Science and Engineering, Frederick Seitz Materials Research Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA; Department of Electrical and Computer Engineering, Frederick Seitz Materials Research Laboratory, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
Michael R Bruchas - Departments of Anesthesiology, Division of Basic Research, Anatomy and Neurobiology, Division of Biomedical Engineering and Washington University Pain Center, Washington University School of Medicine, Saint Louis, MO 63110, USA; Division of Biology and Biomedical Sciences, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: bruchasm@wustl.edu
Resource Type: Journal article
Publication Details: Neuron (Cambridge, Mass.), Vol.87(5), pp.1063-1077
DOI: 10.1016/j.neuron.2015.08.019
PMID: 26335648
PMCID: PMC4625385
NLM abbreviation: Neuron
ISSN: 0896-6273
eISSN: 1097-4199
Publisher: United States
Grant note: F31 MH101956 / NIMH NIH HHS R01DK071051 / NIDDK NIH HHS R01DK096010 / NIDDK NIH HHS P30NS057105 / NINDS NIH HHS R37DK053477 / NIDDK NIH HHS K99 DA038725 / NIDA NIH HHS DA038725 / NIDA NIH HHS P30 DK046200 / NIDDK NIH HHS R01DK089044 / NIDDK NIH HHS R01 DK071051 / NIDDK NIH HHS P60 AA011605 / NIAAA NIH HHS R01 DK096010 / NIDDK NIH HHS R01 DK089044 / NIDDK NIH HHS TR01NS081707 / NINDS NIH HHS R01 DA037152 / NIDA NIH HHS R01DA037152 / NIDA NIH HHS S10 RR027552 / NCRR NIH HHS P30 NS057105 / NINDS NIH HHS R01 NS081707 / NINDS NIH HHS R37 DK053477 / NIDDK NIH HHS S10RR027552 / NCRR NIH HHS P30DK046200 / NIDDK NIH HHS R01 DK075632 / NIDDK NIH HHS R01 DA033396 / NIDA NIH HHS R01DK075632 / NIDDK NIH HHS
Language: English
Date published: 09/02/2015
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology
Record Identifier: 9984040341402771

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