Pathway-specific medium spiny neuron response to chronic L-DOPA treatment in a mouse model of Parkinson's disease.

KEIFMAN E; ESCANDE MV; BELFORTE J; MURER MG

Buenos Aires

Congreso; 2nd FALAN Congress; 2016

FALAN

Medium spiny neurons (MSNs), the main striatal projectionneurons, are key in action selection. It is thought that directpathway MSNs (dMSNs) convey signals that promoteactions, while indirect pathway MSNs (iMSNs) inhibitcompeting actions. Dopamine (DA) promotes movementby favoring cortical action on dMSNs and lessening corticaldrive onto iMSNs. In Parkinson?s disease (PD) nigrostriataldopaminergic neurons degenerate and iMSNs prevail overdMSNs. Chronic treatment with L-DOPA, a DA precursorwidely used to treat PD symptoms, causes structural andfunctional changes in MSNs and up to 50% of patientsdevelop abnormal and incapacitating movements knownas dyskinesia after 5 years of treatment. dMSN overactivityis thought to be responsible for dyskinesia, yet the effects ofL-DOPA on dMSNs and iMSNs have not been studied in vivo indyskinetic animals. Here we explore the electrophysiologicaleffects of L-DOPA on MSN from transgenic mice that showMSN type-specific expression of fluorescent proteins andthat were rendered dyskinetic when treated chronicallywith L-DOPA. We performed in vivo juxtacellular recordingsand we assessed MSN responsiveness to motor cortexstimulation before (off) and following (on) an acute L-DOPAchallenge. We found a significant increase in the responseof dMSNs to cortical input during the on state in L-DOPAtreated animals. In contrast, most iMSNs did not changetheir response to cortical stimulation after an acute L-DOPAchallenge.