title: Restricting dopaminergic signaling to either dorsolateral or medial striatum facilitates cognition.
abstract: Dopaminergic projections to the ventral and dorsomedial striatum are important for reward, motivation, and goal-directed learning, whereas projections to the dorsolateral striatum are implicated in motor control, habitual enactment of motor skills, visuospatial learning, and memory. These conclusions are derived from studies of rodents with lesions or pharmacological blockade of dopamine signaling to specific brain regions. In contrast, we investigated the behavioral abilities of dopamine-deficient mice in which dopamine signaling was restored to only the medial striatum by viral rescue. These mice displayed intact spatial memory, visuospatial and discriminatory learning. However, acquisition of operant behavior was delayed, and their motivation to obtain food rewards was blunted. We compare these behavioral results with our published results obtained from mice with dopamine signaling restored only to the dorsolateral striatum. We observe that most behaviors are restored with dopamine signaling restored to either brain region and conclude that the action of dopamine in either one of these nonoverlapping striatal areas can support cognitive processes independently of dopamine signaling in the other area.
authors.affiliation: Howard Hughes Medical Institute and 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: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D003342:Corpus Striatum / Q000033:anatomy & histology / Q000502:physiology*; D004193:Discrimination Learning / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000172:deficiency / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D018014:Gene Transfer Techniques; D006719:Homovanillic Acid / Q000378:metabolism; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D009483:Neuropsychological Tests; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D015259:Dopamine Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D006719:Homovanillic Acid