Nature Neuroscience 9, 251 - 259 (2006)
Published online: 15 January 2006; | doi:10.1038/nn1632
Selective elimination of glutamatergic synapses on striatopallidal neurons in Parkinson disease modelsMichelle Day1, Zhongfeng Wang1, Jun Ding1, Xinhai An2, Cali A Ingham3, Andrew F Shering3, David Wokosin1, Ema Ilijic1, Zhuoxin Sun4, Allan R Sampson4, Enrico Mugnaini5, Ariel Y Deutch6, Susan R Sesack2, Gordon W Arbuthnott3
& D James Surmeier11
Department of Physiology, 303 East Chicago Avenue, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA. 2
Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. 3
Division of Neuroscience and Veterinary Biomedical Sciences, University of Edinburgh, Summerhall, Edinburgh EH9 1QH, Scotland, UK. 4
Department of Statistics, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA. 5
Department of Cell and Molecular Biology, 303 East Chicago Avenue, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA. 6
Departments of Psychiatry and Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37212, USA.
Correspondence should be addressed to D James Surmeier j-surmeier@northwestern.edu Parkinson disease is a common neurodegenerative disorder that leads to difficulty in effectively translating thought into action. Although it is known that dopaminergic neurons that innervate the striatum die in Parkinson disease, it is not clear how this loss leads to symptoms. Recent work has implicated striatopallidal medium spiny neurons (MSNs) in this process, but how and precisely why these neurons change is not clear. Using multiphoton imaging, we show that dopamine depletion leads to a rapid and profound loss of spines and glutamatergic synapses on striatopallidal MSNs but not on neighboring striatonigral MSNs. This loss of connectivity is triggered by a new mechanism—dysregulation of intraspine Cav1.3 L-type Ca2+ channels. The disconnection of striatopallidal neurons from motor command structures is likely to be a key step in the emergence of pathological activity that is responsible for symptoms in Parkinson disease.
MORE ARTICLES LIKE THIS These links to content published by NPG are automatically generated.
|
