The Timing of Reward-Seeking Action Tracks Visually-Cued Theta Oscillations in Primary Visual Cortex

NAMBOODIRI, VIJAY MOHAN K; ZOLD, CAMILA L.; LEVY, JOSHUA M; HUSSAIN SHULER, MARSHALL G

JOURNAL OF NEUROSCIENCE

SOC NEUROSCIENCE

Lugar: Washington; Año: 2017

0270-6474

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 (42 7% dopaminergic neuron loss) and symptomatic (85 5% 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 firesignificantly more and earlierthan dMSNs. Therefore, cortical driveto dMSNs decreases after partial nigrostriatal lesions producing no behavioralimpairment, but additional alterations in the gain and timing of iMSNs characterize symptomatic rodent parkinsonism.