PMID- 29398356
OWN - NLM
STAT- MEDLINE
DCOM- 20190715
LR  - 20210109
IS  - 1097-4199 (Electronic)
IS  - 0896-6273 (Print)
IS  - 0896-6273 (Linking)
VI  - 97
IP  - 4
DP  - 2018 Feb 21
TI  - A Subpopulation of Striatal Neurons Mediates Levodopa-Induced Dyskinesia.
PG  - 787-795.e6
LID - S0896-6273(18)30020-5 [pii]
LID - 10.1016/j.neuron.2018.01.017 [doi]
AB  - Parkinson's disease is characterized by the progressive loss of midbrain dopamine 
      neurons. Dopamine replacement therapy with levodopa alleviates parkinsonian motor 
      symptoms but is complicated by the development of involuntary movements, termed 
      levodopa-induced dyskinesia (LID). Aberrant activity in the striatum has been 
      hypothesized to cause LID. Here, to establish a direct link between striatal 
      activity and dyskinesia, we combine optogenetics and a method to manipulate 
      dyskinesia-associated neurons, targeted recombination in active populations 
      (TRAP). We find that TRAPed cells are a stable subset of sensorimotor striatal 
      neurons, predominantly from the direct pathway, and that reactivation of TRAPed 
      striatal neurons causes dyskinesia in the absence of levodopa. Inhibition of 
      TRAPed cells, but not a nonspecific subset of direct pathway neurons, ameliorates 
      LID. These results establish that a distinct subset of striatal neurons is 
      causally involved in LID and indicate that successful therapeutic strategies for 
      treating LID may require targeting functionally selective neuronal subtypes.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Girasole, Allison E
AU  - Girasole AE
AD  - Neuroscience Graduate Program, UCSF, San Francisco, CA 94158, USA; Kavli 
      Institute for Fundamental Neuroscience, UCSF, San Francisco, CA 94158, USA; Weill 
      Institute for Neurosciences, UCSF, San Francisco, CA 94158, USA.
FAU - Lum, Matthew Y
AU  - Lum MY
AD  - Department of Neurology, UCSF, San Francisco, CA 94158, USA.
FAU - Nathaniel, Diane
AU  - Nathaniel D
AD  - Department of Neurology, UCSF, San Francisco, CA 94158, USA.
FAU - Bair-Marshall, Chloe J
AU  - Bair-Marshall CJ
AD  - Department of Neurology, UCSF, San Francisco, CA 94158, USA.
FAU - Guenthner, Casey J
AU  - Guenthner CJ
AD  - Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA; 
      Department of Biology, Stanford University, Stanford, CA 94305, USA; 
      Neurosciences Program, Stanford University, Stanford, CA 94305, USA.
FAU - Luo, Liqun
AU  - Luo L
AD  - Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA; 
      Department of Biology, Stanford University, Stanford, CA 94305, USA; 
      Neurosciences Program, Stanford University, Stanford, CA 94305, USA.
FAU - Kreitzer, Anatol C
AU  - Kreitzer AC
AD  - Neuroscience Graduate Program, UCSF, San Francisco, CA 94158, USA; Department of 
      Neurology, UCSF, San Francisco, CA 94158, USA; Department of Physiology, UCSF, 
      San Francisco, CA 94158, USA; Kavli Institute for Fundamental Neuroscience, UCSF, 
      San Francisco, CA 94158, USA; Weill Institute for Neurosciences, UCSF, San 
      Francisco, CA 94158, USA; The Gladstone Institutes, San Francisco, CA 94158, USA.
FAU - Nelson, Alexandra B
AU  - Nelson AB
AD  - Neuroscience Graduate Program, UCSF, San Francisco, CA 94158, USA; Department of 
      Neurology, UCSF, San Francisco, CA 94158, USA; Kavli Institute for Fundamental 
      Neuroscience, UCSF, San Francisco, CA 94158, USA; Weill Institute for 
      Neurosciences, UCSF, San Francisco, CA 94158, USA. Electronic address: 
      alexandra.nelson@ucsf.edu.
LA  - eng
GR  - K08 NS081001/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180201
PL  - United States
TA  - Neuron
JT  - Neuron
JID - 8809320
RN  - 0 (Antiparkinson Agents)
RN  - 46627O600J (Levodopa)
SB  - IM
CIN - Mov Disord. 2018 May;33(5):761. PMID: 29722458
MH  - Animals
MH  - Antiparkinson Agents/*administration & dosage
MH  - Corpus Striatum/drug effects/*physiopathology
MH  - Disease Models, Animal
MH  - Dyskinesia, Drug-Induced/*physiopathology
MH  - Female
MH  - Levodopa/*administration & dosage
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Motor Cortex/drug effects/physiopathology
MH  - Neural Pathways/drug effects/physiopathology
MH  - Neurons/drug effects/*physiology
MH  - Optogenetics
MH  - Parkinson Disease/*physiopathology
PMC - PMC6233726
MID - NIHMS966727
OTO - NOTNLM
OT  - Basal ganglia
OT  - Parkinson's disease
OT  - direct pathway
OT  - dopamine
OT  - levodopa-induced dyskinesia
OT  - optogenetics
EDAT- 2018/02/06 06:00
MHDA- 2019/07/16 06:00
PMCR- 2018/11/13
CRDT- 2018/02/06 06:00
PHST- 2017/05/16 00:00 [received]
PHST- 2017/11/03 00:00 [revised]
PHST- 2018/01/08 00:00 [accepted]
PHST- 2018/02/06 06:00 [pubmed]
PHST- 2019/07/16 06:00 [medline]
PHST- 2018/02/06 06:00 [entrez]
PHST- 2018/11/13 00:00 [pmc-release]
AID - S0896-6273(18)30020-5 [pii]
AID - 10.1016/j.neuron.2018.01.017 [doi]
PST - ppublish
SO  - Neuron. 2018 Feb 21;97(4):787-795.e6. doi: 10.1016/j.neuron.2018.01.017. Epub 
      2018 Feb 1.