Evidence map›Paper›PMID 37461292›Full record

ArticleMovement disorders : official journal of the Movement Disorder Society2023

Substantia Nigra Pars Reticulata Projections to the Pedunculopontine Nucleus Modulate Dyskinesia.

Yong Hu, Thong C Ma, Stephanie L Alberico, Yunmin Ding, Lingjing Jin, Un Jung Kang

Open access · hybridAbstract read
In one paragraph

Article in Movement disorders : official journal of the Movement Disorder Society, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
2.5field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 2 countries.

Yong HuDepartment of Neurology, NYU Grossman School of Medicine, New York, New York, USA.
Thong C MaDepartment of Neurology, NYU Grossman School of Medicine, New York, New York, USA.ORCID 0000-0002-9395-0448
Stephanie L AlbericoDepartment of Neurology, NYU Grossman School of Medicine, New York, New York, USA.
Yunmin DingDepartment of Neurology, NYU Grossman School of Medicine, New York, New York, USA.
Lingjing JinDepartment of Neurology and Neurological Rehabilitation, Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Medicine, Tongji University, Shanghai, China.ORCID 0000-0001-7199-2578
Un Jung KangDepartment of Neurology, NYU Grossman School of Medicine, New York, New York, USA.ORCID 0000-0002-5970-6839
New York University · USShanghai Sunshine Rehabilitation Center · CN

Funding

Pathological striatopallidal neuronalensembles in learned motor impairment in PDR01NS107734 · NINDS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI KANG, UN JUNG · 2018 to 2022
$1.8M
The striatal cholinergic interneurons in Parkinson's disease and treatmentR01NS101982 · NINDS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI KANG, UN JUNG · 2017 to 2020
$1.8M
Regulation of L-DOPA induced dyskinesia by the substantia nigra pars reticulataR21NS108068 · NINDS · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI KANG, UN JUNG · 2018 to 2019
$455k
NINDS NIH HHS R01 NS101982NINDS NIH HHS R01 NS107734NINDS NIH HHS R21 NS108068
6 · The paper itself

Abstract

backgroundLong-term use of levodopa for Parkinson's disease (PD) treatment is often hindered by development of motor complications, including levodopa-induced dyskinesia (LID). The substantia nigra pars reticulata (SNr) and globus pallidus internal segment (GPi) are the output nuclei of the basal ganglia. Dysregulation of SNr and GPi activity contributes to PD pathophysiology and LID.

objectiveThe objective of this study was to determine whether direct modulation of SNr GABAergic neurons and SNr projections to the pedunculopontine nucleus (PPN) regulates PD symptoms and LID in a mouse model.

methodsWe expressed Cre-recombinase activated channelrhodopsin-2 (ChR2) or halorhodopsin adeno-associated virus-2 (AAV2) vectors selectively in SNr GABAergic neurons of Vgat-IRES-Cre mice in a 6-hydroxydopamine model of PD to investigate whether direct optogenetic modulation of SNr neurons or their projections to the PPN regulates PD symptoms and LID expression. The forepaw stepping task, mouse LID rating scale, and open-field locomotion were used to assess akinesia and LID to test the effect of SNr modulation.

resultsAkinesia was improved by suppressing SNr neuron activity with halorhodopsin. LID was significantly reduced by increasing SNr neuronal activity with ChR2, which did not interfere with the antiakinetic effect of levodopa. Optical stimulation of ChR2 in SNr projections to the PPN recapitulated direct SNr stimulation.

conclusionsModulation of SNr GABAergic neurons alters akinesia and LID expression in a manner consistent with the rate model of basal ganglia circuitry. Moreover, the projections from SNr to PPN likely mediate the antidyskinetic effect of increasing SNr neuronal activity, identifying a potential novel role for the PPN in LID. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Indexed as

Dyskinesia, Drug-InducedParkinson DiseasePars ReticulataAnimalsGABAergic NeuronsHalorhodopsinsLevodopaMiceSubstantia NigraHalorhodopsinsLevodopalevodopa-induced dyskinesiaoptogeneticsParkinson's diseasepedunculopontine nucleussubstantia nigra pars reticulata

Identifiers

PMID37461292
PMCPMC10932617
OpenAlexW4384626064

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.