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Cell type-specific plasticity of striatal projection neurons in parkinsonism and L-DOPA-induced dyskinesia.

Fieblinger, Tim LU ; Graves, Steven M; Sebel, Luke E; Alcacer, Cristina LU ; Plotkin, Joshua L; Gertler, Tracy S; Chan, C Savio; Heiman, Myriam; Greengard, Paul and Cenci Nilsson, Angela LU , et al. (2014) In Nature Communications 5.
Abstract
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... (More)
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. (Less)
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Nature Communications
volume
5
publisher
Nature Publishing Group
external identifiers
  • pmid:25360704
  • wos:000344061800002
  • scopus:84920795588
ISSN
2041-1723
DOI
10.1038/ncomms6316
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English
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yes
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ef2dd4ab-48e0-450d-9c1b-74cabff1fdcf (old id 4820461)
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http://www.ncbi.nlm.nih.gov/pubmed/25360704?dopt=Abstract
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2014-12-01 18:28:06
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2017-11-19 03:48:37
@article{ef2dd4ab-48e0-450d-9c1b-74cabff1fdcf,
  abstract     = {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.},
  articleno    = {5316},
  author       = {Fieblinger, Tim and Graves, Steven M and Sebel, Luke E and Alcacer, Cristina and Plotkin, Joshua L and Gertler, Tracy S and Chan, C Savio and Heiman, Myriam and Greengard, Paul and Cenci Nilsson, Angela and Surmeier, D James},
  issn         = {2041-1723},
  language     = {eng},
  publisher    = {Nature Publishing Group},
  series       = {Nature Communications},
  title        = {Cell type-specific plasticity of striatal projection neurons in parkinsonism and L-DOPA-induced dyskinesia.},
  url          = {http://dx.doi.org/10.1038/ncomms6316},
  volume       = {5},
  year         = {2014},
}