title: Acquisition and performance of goal-directed instrumental actions depends on ERK signaling in distinct regions of dorsal striatum in rats.
abstract: The performance of goal-directed actions relies on an animal's previous knowledge of the outcomes or consequences that result from its actions. Additionally, a sensorimotor learning process linking environmental stimuli with actions influences instrumental performance by selecting actions for additional evaluation. These distinct decision-making processes in rodents depend on separate subregions of the dorsal striatum. Whereas the posterior dorsomedial striatum (pDMS) is required for the encoding of actions with their outcomes or consequences, the dorsolateral striatum (DLS) mediates action selection based on sensorimotor learning. However, the molecular mechanisms within these brain regions that support learning and performance of goal-directed behavior are not known. Here we show that activation of extracellular signal-regulated kinase (ERK) in the dorsal striatum has a critical role in learning and performance of instrumental goal-directed behavior in rodents. We observed an increase in p42 ERK (ERK2) activation in both the pDMS and DLS during both the acquisition and performance of recently acquired instrumental goal-directed actions. Furthermore, disruption of ERK activation in the pDMS prevented both the acquisition of action-outcome associations, as well as the performance of goal-directed actions guided by previously acquired associations, whereas disruption of ERK activation in the DLS disrupted instrumental performance but left instrumental action-outcome learning intact. These results provide evidence of a critical, region-specific role for ERK signaling in the dorsal striatum during the acquisition of instrumental learning and suggest that processes sensitive to ERK signaling within these striatal subregions interact to control instrumental performance after initial acquisition.
authors.affiliation: Department of Psychology, University of California, Los Angeles, Los Angeles, California 90095-1563, USA. shiflett@psychology.rutgers.edu
authors.forename: Michael W
authors.initials: MW
authors.lastname: Shiflett
authors.forename: Robert A
authors.initials: RA
authors.lastname: Brown
authors.forename: Bernard W
authors.initials: BW
authors.lastname: Balleine
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D056344:Executive Function / Q000187:drug effects / Q000502:physiology*; D007858:Learning / Q000187:drug effects / Q000502:physiology*; D007859:Learning Disabilities / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009483:Neuropsychological Tests; D009570:Nitriles / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D002070:Butadienes; D004791:Enzyme Inhibitors; D009570:Nitriles; C113580:U 0126; D019950:Mitogen-Activated Protein Kinase 1