@article{3724fc2fb9fe4b359b2998f3dd31c38d,
title = "Selective elimination of glutamatergic synapses on striatopallidal neurons in Parkinson disease models",
abstract = "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.",
author = "Michelle Day and Zhongfeng Wang and Jun Ding and Xinhai An and Ingham, {Cali A.} and Shering, {Andrew F.} and David Wokosin and Ema Ilijic and Zhuoxin Sun and Sampson, {Allan R.} and Enrico Mugnaini and Deutcch, {Ariel Y.} and Sesack, {Susan R.} and Arbuthnott, {Gordon W.} and Surmeier, {D. James}",
note = "Funding Information: We thank P. Penzes, A. Contractor, M. Bevan, H. Kita and C. Wilson for their commentary on our work; T. Tkatch for designing the dopamine receptor primers used to characterize the BAC transgenics; A. Wright, P. Taggert and S. Hood for help with the synapse counts; I. Bezprozvanny for supplying Cav1.3a1 subunit antisera; and N. Heintz, P. Greengard and the National Institute of Neurological Disorders and Stroke Gene Expression Nervous System Atlas (NINDS GENSAT) program for supplying BAC transgenic mice. This work was funded by the US National Institutes of Health (grants NS 34696 and NS 047085 to D.J.S., NS 19608 to S.S. and NS 44282 to A.D.), the Picower Foundation (D.J.S.), the Wellcome Trust and the United Kingdom Parkinson Disease Society (G.W.A. and C.A.I.) and the National Parkinson Foundation Center of Excellence (A.D.).",
year = "2006",
month = feb,
doi = "10.1038/nn1632",
language = "English (US)",
volume = "9",
pages = "251--259",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Publishing Group",
number = "2",
}