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Artículo

Loss of homeostasis in the direct pathway in a mouse model of asymptomatic parkinson’s disease

Escande, Mariela VeronicaIcon ; Taravini, Irene Rita EloisaIcon ; Zold, Camila LidiaIcon ; Belforte, Juan EmilioIcon ; Murer, Mario GustavoIcon
Fecha de publicación: 05/2016
Editorial: Society for Neuroscience
Revista: Journal of Neuroscience
ISSN: 0270-6474
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Neurociencias

Resumen

The characteristic slowness of movement in Parkinson's disease relates to an imbalance in the activity of striatal medium spiny neurons (MSNs) of the direct (dMSNs) and indirect (iMSNs) pathways. However, it is still unclear whether this imbalance emerges during the asymptomatic phase of the disease or if it correlates with symptom severity. Here, we have used in vivo juxtacellular recordings and transgenic mice showing MSN-type-specific expression of fluorescent proteins to examine striatal imbalance after lesioning dopaminergic neurons of the substantia nigra. Multivariate clustering analysis of behavioral data discriminated 2 groups of dopamine-lesioned mice: asymptomatic (42 ± 7% dopaminergic neuron loss) and symptomatic (85 ± 5% cell loss). Contrary to the view that both pathways have similar gain in control conditions, dMSNs respond more intensely than iMSNs to cortical inputs in control animals. Importantly, asymptomatic mice show significant functional disconnection of dMSNs from motor cortex without changes in iMSN connectivity. Moreover, not only the gain but also the timing of the pathways is altered in symptomatic parkinsonism, where iMSNs fire significantly more and earlier than dMSNs. Therefore, cortical drive to dMSNs decreases after partial nigrostriatal lesions producing no behavioral impairment, but additional alterations in the gain and timing of iMSNs characterize symptomatic rodent parkinsonism.
Palabras clave: Parkinson , Ganglios de La Base , Electrofisiologia
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/83126
URL: https://www.jneurosci.org/content/36/21/5686
DOI: https://doi.org/10.1523/JNEUROSCI.0492-15.2016
Colecciones
Articulos(IFIBIO HOUSSAY)
Articulos de INSTITUTO DE FISIOLOGIA Y BIOFISICA BERNARDO HOUSSAY
Citación
Escande, Mariela Veronica; Taravini, Irene Rita Eloisa; Zold, Camila Lidia; Belforte, Juan Emilio; Murer, Mario Gustavo; Loss of homeostasis in the direct pathway in a mouse model of asymptomatic parkinson’s disease; Society for Neuroscience; Journal of Neuroscience; 36; 21; 5-2016; 5686-568698
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