PT  - JOURNAL ARTICLE
AU  - Gourley, Shannon L.
AU  - Olevska, Anastasia
AU  - Gordon, Jessica
AU  - Taylor, Jane R.
TI  - Cytoskeletal Determinants of Stimulus-Response Habits
AID  - 10.1523/JNEUROSCI.1034-13.2013
DP  - 2013 Jul 17
TA  - The Journal of Neuroscience
PG  - 11811--11816
VI  - 33
IP  - 29
4099  - http://www.jneurosci.org/content/33/29/11811.short
4100  - http://www.jneurosci.org/content/33/29/11811.full
SO  - J. Neurosci.2013 Jul 17; 33
AB  - Both humans and rodents can learn to associate specific actions with their outcomes, but with repeated performance or exposure to pathological stimuli, such as drugs of abuse, behaviors assume stimulus-elicited, or “habitual,” qualities. Psychostimulants remodel dorsal striatal neurons, critical determinants of decision-making strategies, but cytoskeletal mechanisms associated with drug-induced habit formation are largely unknown. We first show that cocaine can bias decision-making strategies toward stimulus-response habits by interfering with learning about the predictive relationship between a response and its outcome. In the dorsomedial, but not ventral, striatum, cocaine decreases PSD95 expression and phosphorylation of cortactin, a cytoskeletal regulator that interacts with, and is phophorylated by, the Abl2 (Arg) kinase. Based on this pattern, we inhibited Abl-family kinase signaling in the dorsomedial striatum, impairing new response-outcome learning. Consistent with evidence that the dorsomedial striatum promotes response-outcome decision-making while the dorsolateral compartment promotes stimulus-response habits, inhibition of Abl-family kinases in the dorsolateral striatum reinstates goal sensitivity in over-trained “habitual” mice. These findings provide a structural mechanism by which even acute exposure to drugs of abuse can reorganize behavioral response strategies and promote outcome-insensitive stimulus-response habits.