INVESTIGADORES
BELFORTE Juan Emilio
artículos
Título:
Loss of corticostriatal and thalamostriatal homeostasis in the direct and indirect pathways in mouse Parkinsonism Aceptado
Autor/es:
ESCANDE MV ; TARAVINI IRE; ZOLD, CAMILA; BELFORTE JE * EQUAL CONTRIBUTION; MURER MG *EQUAL CONTRIBUTION
Revista:
JOURNAL OF NEUROSCIENCE
Editorial:
SOC NEUROSCIENCE
Referencias:
Lugar: Washington; Año: 2016 vol. 36 p. 5686 - 568698
ISSN:
0270-6474
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 theasymptomatic phase of the disease or if it correlates with symptom severity. Here, we have used in vivo juxtacellular recordings andtransgenic mice showing MSN-type-specific expression of fluorescent proteins to examine striatal imbalance after lesioning dopaminergicneurons of the substantia nigra. Multivariate clustering analysis of behavioral data discriminated 2 groups of dopamine-lesionedmice: asymptomatic (427% dopaminergic neuron loss) and symptomatic (855% cell loss). Contrary to the view that both pathwayshave 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 significantlymore and earlier than dMSNs. Therefore, cortical drive to dMSNs decreases after partial nigrostriatal lesions producing no behavioralimpairment, but additional alterations in the gain and timing of iMSNs characterize symptomatic rodent parkinsonism.