Article abstract
Nature Neuroscience 10, 1458 - 1466 (2007)
Published online: 30 September 2007 | doi:10.1038/nn1972
Cholinergic modulation of Kir2 channels selectively elevates dendritic excitability in striatopallidal neurons
Weixing Shen1, Xinyong Tian1, Michelle Day1, Sasha Ulrich1, Tatiana Tkatch1, Neil M Nathanson2 & D James Surmeier1
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.
- Department of Physiology and Institute of Neuroscience, Feinberg School of Medicine, Northwestern University, 303 E. Chicago Ave., Chicago, Illinois 60611, USA.
- Department of Pharmacology, University of Washington School of Medicine, Seattle, Washington 98195, USA.
Correspondence to: D James Surmeier1 e-mail: j-surmeier@northwestern.edu
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
NEWS AND VIEWS
Indirect-pathway neurons lose their spines in Parkinson diseaseNature Neuroscience News and Views (01 Feb 2006)
RESEARCH
Cholinergic modulation of Kir2 channels selectively elevates dendritic excitability in striatopallidal neuronsNature Neuroscience Article
Selective elimination of glutamatergic synapses on striatopallidal neurons in Parkinson disease modelsNature Neuroscience Article (01 Feb 2006)
Endocannabinoid-mediated rescue of striatal LTD and motor deficits in Parkinson's disease modelsNature Letters to Editor (08 Feb 2007)
See all 29 matches for Research
