State transitions in the substantia nigra reticulata predict the onset of motor deficits in models of progressive dopamine depletion in mice

Amanda M. Willard, Brian R. Isett, Timothy C. Whalen, Kevin J. Mastro, Chris S. Ki, Xiaobo Mao, Aryn H. Gittis

Research output: Contribution to journalArticle

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder whose cardinal motor symptoms are attributed to dysfunction of basal ganglia circuits under conditions of low dopamine. Despite well-established physiological criteria to define basal ganglia dysfunction, correlations between individual parameters and motor symptoms are often weak, challenging their predictive validity and causal contributions to behavior. One limitation is that basal ganglia pathophysiology is studied only at end-stages of depletion, leaving an impoverished understanding of when deficits emerge and how they evolve over the course of depletion. In this study, we use toxin- and neurodegeneration-induced mouse models of dopamine depletion to establish the physiological trajectory by which the substantia nigra reticulata (SNr) transitions from the healthy to the diseased state. We find that physiological progression in the SNr proceeds in discrete state transitions that are highly stereotyped across models and correlate well with the prodromal and symptomatic stages of behavior.

Original languageEnglish (US)
Article numbere42746
JournaleLife
Volume8
DOIs
StatePublished - Mar 1 2019

Fingerprint

Basal Ganglia
Dopamine
Prodromal Symptoms
Trajectories
Neurodegenerative Diseases
Parkinson Disease
Networks (circuits)
Pars Reticulata

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

State transitions in the substantia nigra reticulata predict the onset of motor deficits in models of progressive dopamine depletion in mice. / Willard, Amanda M.; Isett, Brian R.; Whalen, Timothy C.; Mastro, Kevin J.; Ki, Chris S.; Mao, Xiaobo; Gittis, Aryn H.

In: eLife, Vol. 8, e42746, 01.03.2019.

Research output: Contribution to journalArticle

Willard, Amanda M. ; Isett, Brian R. ; Whalen, Timothy C. ; Mastro, Kevin J. ; Ki, Chris S. ; Mao, Xiaobo ; Gittis, Aryn H. / State transitions in the substantia nigra reticulata predict the onset of motor deficits in models of progressive dopamine depletion in mice. In: eLife. 2019 ; Vol. 8.
@article{eb85de77079a498ca0f62b45229e7158,
title = "State transitions in the substantia nigra reticulata predict the onset of motor deficits in models of progressive dopamine depletion in mice",
abstract = "Parkinson’s disease (PD) is a progressive neurodegenerative disorder whose cardinal motor symptoms are attributed to dysfunction of basal ganglia circuits under conditions of low dopamine. Despite well-established physiological criteria to define basal ganglia dysfunction, correlations between individual parameters and motor symptoms are often weak, challenging their predictive validity and causal contributions to behavior. One limitation is that basal ganglia pathophysiology is studied only at end-stages of depletion, leaving an impoverished understanding of when deficits emerge and how they evolve over the course of depletion. In this study, we use toxin- and neurodegeneration-induced mouse models of dopamine depletion to establish the physiological trajectory by which the substantia nigra reticulata (SNr) transitions from the healthy to the diseased state. We find that physiological progression in the SNr proceeds in discrete state transitions that are highly stereotyped across models and correlate well with the prodromal and symptomatic stages of behavior.",
author = "Willard, {Amanda M.} and Isett, {Brian R.} and Whalen, {Timothy C.} and Mastro, {Kevin J.} and Ki, {Chris S.} and Xiaobo Mao and Gittis, {Aryn H.}",
year = "2019",
month = "3",
day = "1",
doi = "10.7554/eLife.42746",
language = "English (US)",
volume = "8",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",

}

TY - JOUR

T1 - State transitions in the substantia nigra reticulata predict the onset of motor deficits in models of progressive dopamine depletion in mice

AU - Willard, Amanda M.

AU - Isett, Brian R.

AU - Whalen, Timothy C.

AU - Mastro, Kevin J.

AU - Ki, Chris S.

AU - Mao, Xiaobo

AU - Gittis, Aryn H.

PY - 2019/3/1

Y1 - 2019/3/1

N2 - Parkinson’s disease (PD) is a progressive neurodegenerative disorder whose cardinal motor symptoms are attributed to dysfunction of basal ganglia circuits under conditions of low dopamine. Despite well-established physiological criteria to define basal ganglia dysfunction, correlations between individual parameters and motor symptoms are often weak, challenging their predictive validity and causal contributions to behavior. One limitation is that basal ganglia pathophysiology is studied only at end-stages of depletion, leaving an impoverished understanding of when deficits emerge and how they evolve over the course of depletion. In this study, we use toxin- and neurodegeneration-induced mouse models of dopamine depletion to establish the physiological trajectory by which the substantia nigra reticulata (SNr) transitions from the healthy to the diseased state. We find that physiological progression in the SNr proceeds in discrete state transitions that are highly stereotyped across models and correlate well with the prodromal and symptomatic stages of behavior.

AB - Parkinson’s disease (PD) is a progressive neurodegenerative disorder whose cardinal motor symptoms are attributed to dysfunction of basal ganglia circuits under conditions of low dopamine. Despite well-established physiological criteria to define basal ganglia dysfunction, correlations between individual parameters and motor symptoms are often weak, challenging their predictive validity and causal contributions to behavior. One limitation is that basal ganglia pathophysiology is studied only at end-stages of depletion, leaving an impoverished understanding of when deficits emerge and how they evolve over the course of depletion. In this study, we use toxin- and neurodegeneration-induced mouse models of dopamine depletion to establish the physiological trajectory by which the substantia nigra reticulata (SNr) transitions from the healthy to the diseased state. We find that physiological progression in the SNr proceeds in discrete state transitions that are highly stereotyped across models and correlate well with the prodromal and symptomatic stages of behavior.

UR - http://www.scopus.com/inward/record.url?scp=85062625592&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062625592&partnerID=8YFLogxK

U2 - 10.7554/eLife.42746

DO - 10.7554/eLife.42746

M3 - Article

C2 - 30839276

AN - SCOPUS:85062625592

VL - 8

JO - eLife

JF - eLife

SN - 2050-084X

M1 - e42746

ER -