Selective elimination of glutamatergic synapses on striatopallidal neurons in Parkinson disease models.
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 Ca(2+) 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.
Day
Michelle
M
Department of Physiology, 303 East Chicago Avenue, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Wang
Zhongfeng
Z
Ding
Jun
J
An
Xinhai
X
Ingham
Cali A
CA
Shering
Andrew F
AF
Wokosin
David
D
Ilijic
Ema
E
Sun
Zhuoxin
Z
Sampson
Allan R
AR
Mugnaini
Enrico
E
Deutch
Ariel Y
AY
Sesack
Susan R
SR
Arbuthnott
Gordon W
GW
Surmeier
D James
DJ
D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism; D003342:Corpus Striatum / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D049229:Dendritic Spines / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D004195:Disease Models, Animal; D005973:Glutamine / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016253:Microscopy, Immunoelectron; D009434:Neural Pathways / Q000378:metabolism / Q000473:pathology*; D009924:Organ Culture Techniques; D010300:Parkinson Disease / Q000473:pathology / Q000503:physiopathology*; D018408:Patch-Clamp Techniques; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure
D020746:Calcium Channels, L-Type; D005973:Glutamine