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Neuron. 2016 Jun 15;90(6):1312-1324. doi: 10.1016/j.neuron.2016.04.043. Epub 2016 May 26.

Endocannabinoid Modulation of Orbitostriatal Circuits Gates Habit Formation.

Author information

1
Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA; Department of Psychology, Neuroscience Graduate Program, University of California San Diego, La Jolla, CA 92093, USA.
2
Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA.
3
Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
4
Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
5
Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: lovindav@mail.nih.gov.
6
Champalimaud Neuroscience Programme, Champalimaud Institute for the Unknown, Lisbon 1400-038, Portugal. Electronic address: rui.costa@neuro.fchampalimaud.org.

Abstract

Everyday function demands efficient and flexible decision-making that allows for habitual and goal-directed action control. An inability to shift has been implicated in disorders with impaired decision-making, including obsessive-compulsive disorder and addiction. Despite this, our understanding of the specific molecular mechanisms and circuitry involved in shifting action control remains limited. Here we identify an endogenous molecular mechanism in a specific cortical-striatal pathway that mediates the transition between goal-directed and habitual action strategies. Deletion of cannabinoid type 1 (CB1) receptors from cortical projections originating in the orbital frontal cortex (OFC) prevents mice from shifting from goal-directed to habitual instrumental lever pressing. Activity of OFC neurons projecting to dorsal striatum (OFC-DS) and, specifically, activity of OFC-DS terminals is necessary for goal-directed action control. Lastly, CB1 deletion from OFC-DS neurons prevents the shift from goal-directed to habitual action control. These data suggest that the emergence of habits depends on endocannabinoid-mediated attenuation of a competing circuit controlling goal-directed behaviors.

PMID:
27238866
PMCID:
PMC4911264
DOI:
10.1016/j.neuron.2016.04.043
[Indexed for MEDLINE]
Free PMC Article

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