title: Contributions of striatal dopamine signaling to the modulation of cognitive flexibility.
abstract: BACKGROUND
  Although cognitive flexibility is mediated by different areas of the prefrontal cortex, evidence from patients with Parkinson's disease suggests an additional involvement of striatal dopamine (DA) signaling. Because both dorsal and ventral striatum receive prefrontal cortex projections, it is unclear whether DA signaling to either one or both of these regions is required for cognitive flexibility.
  
  
  METHODS
  Cognitive flexibility was examined with a water U-maze paradigm in which mice had to shift from an initially acquired escape strategy to a new strategy or to reverse the initially learned strategy. We tested mice with conditionally inactive tyrosine hydroxylase genes that can be activated by Cre recombinase. With region-specific viral gene therapy we selectively restricted DA signaling to either dorsal or ventral striatum.
  
  
  RESULTS
  Restricting DA signaling to the ventral striatum did not impair learning of the initial strategy or reversal-learning but strongly disrupted strategy-shifting. In contrast, mice with DA signaling restricted to the dorsal striatum had intact learning of the initial strategy, reversal-learning, and strategy-shifting.
  
  
  CONCLUSIONS
  Dopamine signaling in both dorsal and ventral striatum is sufficient for reversal-learning, whereas only DA signaling in the dorsal striatum is sufficient for the more demanding strategy-shifting task.
authors.affiliation: Department of Biochemistry, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Darvas
authors.forename: Richard D
authors.initials: RD
authors.lastname: Palmiter
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D002755:Choice Behavior / Q000502:physiology; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000172:deficiency / Q000378:metabolism*; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D049691:History, Medieval; D019426:Integrases / Q000235:genetics; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012193:Reversal Learning / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000172:deficiency / Q000378:metabolism
chemical_list: D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase; C045073:Cre recombinase; D019426:Integrases; D004298:Dopamine