Cell type-specific plasticity of striatal projection neurons in parkinsonism and L-DOPA-induced dyskinesia
Author(s)Fieblinger, Tim; Graves, Steven M.; Sebel, Luke E.; Alcacer, Cristina; Plotkin, Joshua L.; Gertler, Tracy S.; Chan, C. Savio; Heiman, Myriam; Greengard, Paul; Cenci, M. Angela; Surmeier, D. James; ... Show more Show less
MetadataShow full item record
The striatum is widely viewed as the fulcrum of pathophysiology in Parkinson’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.
DepartmentMassachusetts Institute of Technology. Department of Brain and Cognitive Sciences; Picower Institute for Learning and Memory
Nature Publishing Group
Fieblinger, Tim, Steven M. Graves, Luke E. Sebel, Cristina Alcacer, Joshua L. Plotkin, Tracy S. Gertler, C. Savio Chan, et al. “Cell Type-Specific Plasticity of Striatal Projection Neurons in Parkinsonism and L-DOPA-Induced Dyskinesia.” Nat Comms 5 (October 31, 2014): 5316.
Author's final manuscript