Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Disrupted basal ganglia output during movement preparation in hemi-parkinsonian mice accounts for behavioral deficits

View ORCID ProfileAnand Tekriwal, View ORCID ProfileMario J. Lintz, View ORCID ProfileJohn A. Thompson, View ORCID ProfileGidon Felsen
doi: https://doi.org/10.1101/2020.06.19.160457
Anand Tekriwal
1Department of Physiology and Biophysics, University of Colorado School of Medicine, Aurora, CO 80045
2Department of Neurosurgery, University of Colorado School of Medicine, Aurora, CO 80045
5Neuroscience Program, University of Colorado School of Medicine, Aurora, CO 80045
6Medical Scientist Training Program, University of Colorado School of Medicine, Aurora, CO 80045
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Anand Tekriwal
Mario J. Lintz
1Department of Physiology and Biophysics, University of Colorado School of Medicine, Aurora, CO 80045
3Department of Psychiatry, University of Colorado School of Medicine, Aurora, CO 80045
5Neuroscience Program, University of Colorado School of Medicine, Aurora, CO 80045
6Medical Scientist Training Program, University of Colorado School of Medicine, Aurora, CO 80045
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Mario J. Lintz
John A. Thompson
2Department of Neurosurgery, University of Colorado School of Medicine, Aurora, CO 80045
4Department of Neurology, University of Colorado School of Medicine, Aurora, CO 80045
5Neuroscience Program, University of Colorado School of Medicine, Aurora, CO 80045
6Medical Scientist Training Program, University of Colorado School of Medicine, Aurora, CO 80045
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for John A. Thompson
Gidon Felsen
1Department of Physiology and Biophysics, University of Colorado School of Medicine, Aurora, CO 80045
5Neuroscience Program, University of Colorado School of Medicine, Aurora, CO 80045
6Medical Scientist Training Program, University of Colorado School of Medicine, Aurora, CO 80045
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Gidon Felsen
  • For correspondence: gidon.felsen@cuanschutz.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

ABSTRACT

Parkinsonian motor deficits are associated with elevated inhibitory output from the basal ganglia (BG). However, several features of Parkinson’s disease (PD) have not been accounted for by this supra-inhibition framework, including the potentially therapeutically-relevant observation that movements guided by external stimuli are less impaired than otherwise-identical movements generated based on internal goals. Is this difference due to divergent processing within the BG itself, or to the recruitment of extra-BG pathways by sensory processing? In addition, surprisingly little is known about precisely when, in the sequence from selecting to executing movements, BG output is altered by PD. Here, we address these questions by recording activity in the SNr, a key BG output nucleus, in hemiparkinsonian (hemi-PD) mice performing a well-controlled behavioral task requiring stimulus-guided and internally-specified directional movements. We found that hemi-PD mice (n = 5, male) exhibited a bias ipsilateral to the side of dopaminergic cell loss, consistent with supra-inhibition of contralateral movements by BG output, and that this bias was stronger when movements were internally specified rather than stimulus guided, consistent with clinical observations in parkinsonian patients. We further found that changes in SNr activity during movement preparation could account for the ipsilateral behavioral bias, as well as its greater magnitude for internally-specified movements. These results suggest that parkinsonian changes in BG output underlying movement preparation contribute to the greater deficit in internally-specified in comparison to stimulus-guided movements.

Significance Statement Parkinsonian patients exhibit the intriguing phenomenon that movements guided by external stimuli are often less impaired than otherwise-identical movements generated based on internal goals. For example, patients can exhibit a more normal gait when their steps are guided by patterned floor tiling than when traversing a featureless floor. Whether this difference in movement execution is due to distinct processing intrinsic to the basal ganglia (BG) or to compensation from other motor pathways is an open question with therapeutic implications. We addressed this question by recording BG output during behavior in a parkinsonian mouse model. We found that mice exhibited greater impairment in internally-specified than stimulus-guided movements, and that differences in BG output during movement preparation could account for this effect.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted June 20, 2020.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Disrupted basal ganglia output during movement preparation in hemi-parkinsonian mice accounts for behavioral deficits
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Disrupted basal ganglia output during movement preparation in hemi-parkinsonian mice accounts for behavioral deficits
Anand Tekriwal, Mario J. Lintz, John A. Thompson, Gidon Felsen
bioRxiv 2020.06.19.160457; doi: https://doi.org/10.1101/2020.06.19.160457
Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Disrupted basal ganglia output during movement preparation in hemi-parkinsonian mice accounts for behavioral deficits
Anand Tekriwal, Mario J. Lintz, John A. Thompson, Gidon Felsen
bioRxiv 2020.06.19.160457; doi: https://doi.org/10.1101/2020.06.19.160457

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Neuroscience
Subject Areas
All Articles
  • Animal Behavior and Cognition (2505)
  • Biochemistry (4951)
  • Bioengineering (3452)
  • Bioinformatics (15127)
  • Biophysics (6854)
  • Cancer Biology (5357)
  • Cell Biology (7681)
  • Clinical Trials (138)
  • Developmental Biology (4502)
  • Ecology (7110)
  • Epidemiology (2059)
  • Evolutionary Biology (10178)
  • Genetics (7491)
  • Genomics (9750)
  • Immunology (4801)
  • Microbiology (13131)
  • Molecular Biology (5109)
  • Neuroscience (29289)
  • Paleontology (203)
  • Pathology (832)
  • Pharmacology and Toxicology (1454)
  • Physiology (2116)
  • Plant Biology (4714)
  • Scientific Communication and Education (1002)
  • Synthetic Biology (1332)
  • Systems Biology (3993)
  • Zoology (766)