Exploring the Impact of Parkinson’s on Brain Circuits in Rats

Published on May 23, 2022

Parkinson’s disease affects brain circuits involved in movement. In this study, scientists investigated how the parafascicular nucleus (PF) in the thalamus and the motor cortex (M1) interacted in rats with Parkinson’s-like symptoms. They found that the firing patterns of PF neurons and the oscillatory activity in M1 were altered in the hemiparkinsonian rats. The neurons in PF exhibited abnormal firing rates and synchronized their firing with the oscillations in M1 at beta frequencies. The phase-locking at different frequencies was decreased in both PF and M1. The study also revealed bidirectional connections between PF and M1. These findings suggest that Parkinson’s disease affects the anatomical and functional interactions between PF and M1, which depend on frequency, behavioral state, and the integrity of the dopaminergic system.

Parkinson’s disease (PD) is characterized by aberrant discharge patterns and exaggerated oscillatory activity within basal ganglia-thalamocortical circuits. We have previously observed substantial alterations in spike and local field potential (LFP) activities recorded in the thalamic parafascicular nucleus (PF) and motor cortex (M1), respectively, of hemiparkinsonian rats during rest or catching movements. This study explored whether the mutual effects of the PF and M1 depended on the amplitude and phase relationship in their identified neuron spikes or group rhythmic activities. Microwire electrode arrays were paired and implanted in the PF and M1 of rats with unilateral dopaminergic cell lesions. The results showed that the identified PF neurons exhibited aberrant cell type-selective firing rates and preferential and excessive phase-locked firing to cortical LFP oscillations mainly at 12–35 Hz (beta frequencies), consistent with the observation of identified M1 neurons with ongoing PF LFP oscillations. Experimental evidence also showed a decrease in phase-locking at 0.7–12 Hz and 35–70 Hz in the PF and M1 circuits in the hemiparkinsonian rats. Furthermore, anatomical evidence was provided for the existence of afferent and efferent bidirectional reciprocal connectivity pathways between the PF and M1 using an anterograde and retrograde neuroanatomical tracing virus. Collectively, our results suggested that multiple alterations may be present in regional anatomical and functional modes with which the PF and M1 interact, and that parkinsonism-associated changes in PF integrate M1 activity in a manner that varies with frequency, behavioral state, and integrity of the dopaminergic system.

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