MEF-2 regulates activity-dependent spine loss in striatopallidal medium spiny neurons

Xinyong Tian, Li Kai, Philip E. Hockberger, David L. Wokosin, D. James Surmeier*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

Striatal dopamine depletion profoundly reduces the density of spines and corticostriatal glutamatergic synapses formed on D2 dopamine receptor expressing striatopallidal medium spiny neurons, leaving D1 receptor expressing striatonigral medium spiny neurons relatively intact. Because D2 dopamine receptors diminish the excitability of striatopallidal MSNs, the pruning of synapses could be a form of homeostatic plasticity aimed at restoring activity into a preferred range. To characterize the homeostatic mechanisms controlling synapse density in striatal medium spiny neurons, striatum from transgenic mice expressing a D2 receptor reporter construct was co-cultured with wild-type cerebral cortex. Sustained depolarization of these co-cultures induced a profound pruning of glutamatergic synapses and spines in striatopallidal medium spiny neurons. This pruning was dependent upon Ca2+ entry through Cav1.2 L-type Ca2+ channels, activation of the Ca2+-dependent protein phosphatase calcineurin and up-regulation of myocyte enhancer factor 2 (MEF2) transcriptional activity. Depolarization and MEF2 up-regulation increased the expression of two genes linked to synaptic remodeling-Nur77 and Arc. Taken together, these studies establish a translational framework within which striatal adaptations linked to the symptoms of Parkinson's disease can be explored.

Original languageEnglish
Pages (from-to)94-108
Number of pages15
JournalMolecular and Cellular Neuroscience
Volume44
Issue number1
DOIs
StatePublished - May 2010

Keywords

  • Dendritic spine
  • GABA
  • Parkinson's disease
  • Patch clamp
  • Plasticity
  • Striatum

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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