The striatum is widely viewed as the fulcrum of pathophysiology in Parkinsonâ €™ s disease (PD) and L-DOPA-induced dyskinesia (LID). In these disease states, the balance in activity of striatal direct pathway spiny projection neurons (dSPNs) and indirect pathway spiny projection neurons (iSPNs) is disrupted, leading to aberrant action selection. However, it is unclear whether countervailing mechanisms are engaged in these states. Here we report that iSPN intrinsic excitability and excitatory corticostriatal synaptic connectivity were lower in PD models than normal; L-DOPA treatment restored these properties. Conversely, dSPN intrinsic excitability was elevated in tissue from PD models and suppressed in LID models. Although the synaptic connectivity of dSPNs did not change in PD models, it fell with L-DOPA treatment. In neither case, however, was the strength of corticostriatal connections globally scaled. Thus, SPNs manifested homeostatic adaptations in intrinsic excitability and in the number but not strength of excitatory corticostriatal synapses.
Bibliographical noteFunding Information:
This study was supported by USPHSG NS34696, NS041234, NS084735 and the JPB Foundation to D.J.S. and P.G., the IDP foundation to D.J.S. and by grants to M.A.C. from the European Community‘s Seventh Framework Programme FP7, the Basal Ganglia Disorders Linnaeus Consortium (BAGADILICO), the Swedish Research Council, the Swedish Foundation for International Cooperation in Research and Higher Education (STINT), and the Olle Engkvist Foundation.
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