Endocannabinoid Modulation of Orbitostriatal Circuits Gates Habit Formation

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

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Clozapine / analogs & derivatives
  • Clozapine / pharmacology
  • Conditioning, Operant*
  • Corpus Striatum / physiology*
  • Endocannabinoids / physiology*
  • Gene Knockdown Techniques
  • Habits*
  • Male
  • Mice
  • Neural Inhibition / physiology
  • Neural Pathways / drug effects
  • Neural Pathways / physiology
  • Prefrontal Cortex / physiology*
  • Receptor, Cannabinoid, CB1 / genetics
  • Receptor, Cannabinoid, CB1 / physiology*

Substances

  • Endocannabinoids
  • Receptor, Cannabinoid, CB1
  • Clozapine
  • clozapine N-oxide