Aberrant striatal plasticity is specifically associated with dyskinesia following levodopa treatment.
Chronic levodopa treatment for Parkinson's disease often results in the development of abnormal involuntary movement, known as L-dopa-induced dyskinesia (LIDs). Studies suggest that LIDs may be associated with aberrant corticostriatal plasticity. Using in vivo extracellular recordings from identified Type I and Type II medium spiny striatal neurons, chronic L-dopa treatment was found to produce abnormal corticostriatal information processing. Specifically, after chronic L-dopa treatment in dopamine-depleted rats, there was a transition from a cortically evoked long-term depression (LTD) to a complementary but opposing form of plasticity, long-term potentiation, in Type II "indirect" pathway neurons. In contrast, LTD could still be induced in Type I neurons. Interestingly, the one parameter that correlated best with dyskinesias was the inability to de-depress established LTD in Type I medium spiny striatal neurons. Taken as a whole, we propose that the induction of LIDs is due, at least in part, to an aberrant induction of plasticity within the Type II indirect pathway neurons combined with an inability to de-depress established plastic responses in Type I neurons. Such information is critical for understanding the cellular mechanisms underlying one of the major caveats to L-dopa therapy.
Belujon
Pauline
P
Departments of Neuroscience, Psychiatry, and Psychology, University of Pittsburgh, Pittsburgh, PA 15260, USA. belujon@pitt.edu
Lodge
Daniel J
DJ
Grace
Anthony A
AA
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects*; D001522:Behavior, Animal / Q000187:drug effects; D002772:Cholera Toxin / Q000378:metabolism; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology*; D004195:Disease Models, Animal; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology*; D005456:Fluorescent Dyes / Q000378:metabolism; D007980:Levodopa / Q000009:adverse effects*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000188:drug therapy / Q000209:etiology; D051381:Rats; D013378:Substantia Nigra / Q000187:drug effects / Q000503:physiopathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000978:Antiparkinson Agents; D005456:Fluorescent Dyes; D007980:Levodopa; D016627:Oxidopamine; D002772:Cholera Toxin; D014446:Tyrosine 3-Monooxygenase