Endocannabinoid Modulation of Orbitostriatal Circuits Gates Habit Formation NEURON Gremel, C. M., Chancey, J. H., Atwood, B. K., Luo, G., Neve, R., Ramakrishnan, C., Deisseroth, K., Lovinger, D. M., Costa, R. M. 2016; 90 (6): 1312-1324

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.

View details for DOI 10.1016/j.neuron.2016.04.043

View details for Web of Science ID 000378527600018

View details for PubMedID 27238866

View details for PubMedCentralID PMC4911264