Cholinergic modulation of Kir2 channels selectively elevates dendritic excitability in striatopallidal neurons

Weixing Shen, Xinyong Tian, Michelle Day, Sasha Ulrich, Tatiana Tkatch, Neil M. Nathanson, D. James Surmeier*

*Corresponding author for this work

Research output: Contribution to journalArticle

166 Scopus citations

Abstract

Dopamine-depleting lesions of the striatum that mimic Parkinson's disease induce a profound pruning of spines and glutamatergic synapses in striatopallidal medium spiny neurons, leaving striatonigral medium spiny neurons intact. The mechanisms that underlie this cell type-specific loss of connectivity are poorly understood. The Kir2 K+ channel is an important determinant of dendritic excitability in these cells. Here we show that opening of these channels is potently reduced by signaling through M1 muscarinic receptors in striatopallidal neurons, but not in striatonigral neurons. This asymmetry could be attributed to differences in the subunit composition of Kir2 channels. Dopamine depletion alters the subunit composition further, rendering Kir2 channels in striatopallidal neurons even more susceptible to modulation. Reduced opening of Kir2 channels enhances dendritic excitability and synaptic integration. This cell type-specific enhancement of dendritic excitability is an essential trigger for synaptic pruning after dopamine depletion, as pruning was prevented by genetic deletion of M1 muscarinic receptors.

Original languageEnglish (US)
Pages (from-to)1458-1466
Number of pages9
JournalNature Neuroscience
Volume10
Issue number11
DOIs
StatePublished - Nov 1 2007

ASJC Scopus subject areas

  • Neuroscience(all)

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