State transitions in the substantia nigra reticulata predict the onset of motor deficits in models of progressive dopamine depletion in mice.
Elife
; 82019 03 06.
Article
em En
| MEDLINE
| ID: mdl-30839276
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dopamina
/
Doenças Neurodegenerativas
/
Parte Reticular da Substância Negra
/
Transtornos Motores
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article