Differential excitability and modulation of striatal medium spiny neuron dendrites

Michelle Day, David Wokosin, Joshua L. Plotkin, Xinyoung Tian, D. James Surmeier

Research output: Contribution to journalArticlepeer-review

164 Scopus citations

Abstract

The loss of striatal dopamine (DA) in Parkinson's disease (PD) models triggers a cell-type-specific reduction in the density of dendritic spines in D2 receptor-expressing striatopallidal medium spiny neurons (D 2 MSNs). How the intrinsic properties of MSN dendrites, where the vast majority of DA receptors are found, contribute to this adaptation is not clear. To address this question, two-photon laser scanning microscopy (2PLSM) was performed in patch-clamped mouse MSNs identified in striatal slices by expression of green fluorescent protein (eGFP) controlled by DA receptor promoters. These studies revealed that single backpropagating action potentials (bAPs) produced more reliable elevations in cytosolic Ca2+ concentration at distal dendritic locations in D2 MSNs than at similar locations in D1 receptor-expressing striatonigral MSNs (D1 MSNs). In both cell types, the dendritic Ca2+ entry elicited by bAPs was enhanced by pharmacological blockade of Kv4, but not Kv1K+ channels. Local application of DA depressed dendritic bAP-evoked Ca2+ transients, whereas application of ACh increased these Ca2+ transients in D2 MSNs, but not in D1 MSNs. After DA depletion, bAP-evoked Ca2+ transients were enhanced in distal dendrites and spines in D2 MSNs. Together, these results suggest that normally D2 MSN dendrites are more excitable than those of D1 MSNs and that DA depletion exaggerates this asymmetry, potentially contributing to adaptations in PD models.

Original languageEnglish (US)
Pages (from-to)11603-11614
Number of pages12
JournalJournal of Neuroscience
Volume28
Issue number45
DOIs
StatePublished - Nov 5 2008

Keywords

  • Acetylcholine
  • Dopamine
  • Glutamatergic synapse
  • Medium spiny neuron
  • Parkinson's disease
  • Potassium channels
  • Striatum

ASJC Scopus subject areas

  • Neuroscience(all)

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