Graded 6-OHDA-induced dopamine depletion in the nigrostriatal pathway evokes progressive pathological neuronal activities in the subthalamic nucleus of a hemi-parkinsonian mouse.
Behav Brain Res
; 344: 42-47, 2018 05 15.
Article
en En
| MEDLINE
| ID: mdl-29452192
ABSTRACT
Recent studies have established methods for establishing a rodent model that mimics progressive stages of human Parkinson's disease (PD), via injection of graded doses of 6-hydroxydopamine (6-OHDA) into regions within the nigrostriatal pathway. However, the electrophysiological characteristics of the subthalamic nucleus (STN) in this model have not been fully elucidated in this model. This study aimed to investigate changes in the neuronal activity of the STN in a graded mouse model of PD. Increasing doses of 6-OHDA were unilaterally injected into the medial forebrain bundle (MFB) to produce a hemi-parkinsonian mouse model, mimicking early, moderate, advanced, and severe stages of human PD. Mice treated with higher doses of 6-OHDA demonstrated significantly lower rates of use of the impaired (contralateral) forelimb during wall contact, relative to sham mice. The STN firing rate was significantly increased in groups with >75% dopaminergic cell loss in the substantia nigra pars compacta (SNc), whereas little increase was observed in groups with partial lesions of the SNc, relative to the sham group. In addition, firing patterns of the STN in groups treated with higher doses of 6-OHDA became more irregular and exhibited burst-like patterns of activity, with dominant slow wave oscillations in the frequency range of 0.3-2.5â¯Hz. Our results demonstrated a strong correlation between neuronal activities in the STN and dopamine depletion in the nigrostriatal pathway, which can be manipulated by variation of 6-OHDA doses.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Potenciales de Acción
/
Dopamina
/
Núcleo Subtalámico
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Trastornos Parkinsonianos
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Neuronas Dopaminérgicas
/
Porción Compacta de la Sustancia Negra
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Behav Brain Res
Año:
2018
Tipo del documento:
Article