Functional Interactions Between the Parafascicular Thalamic Nucleus and Motor Cortex Are Altered in Hemiparkinsonian Rat

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.

Automated summary

Parkinson's disease is associated with abnormal activity patterns and oscillations in the brain's basal ganglia-thalamocortical circuits. This study investigated the interaction between the thalamic parafascicular nucleus (PF) and motor cortex (M1) in rats with dopaminergic cell lesions. The results showed aberrant firing patterns and phase-locked firing in PF neurons, which correlated with ongoing PF oscillations in M1 neurons. There were also alterations in phase-locking in both PF and M1 circuits in the diseased rats. The study provided evidence for bidirectional connectivity pathways between PF and M1. These findings suggest that multiple alterations in anatomical and functional modes may contribute to the interaction between PF and M1 in Parkinson's disease.