Abstract
Parkinson’s disease (PD) is the second most common debilitating neurologic disease after Alzheimer’s disease globally. In this study, rats whose midbrain dopaminergic neurons have been depleted unilaterally, called as hemi-Parkinsonian rats, are used as a model. By local field potential (LFP) recording, we detect alterations in the activities in the primary motor cortex, M1, of freely moving hemi Parkinsonian rats. These alterations include the presence of exacerbated oscillations in the β‐regime and the more frequent appearance of high voltage spindle episodes (HVSs). Application of high-frequency, 130 Hz, stimulation applied on the subthalamic nucleus (STN-HFS) is used to mimic the DBS treatment that is widely used to treat advanced Parkinson’s disease. Application of STN-HFS in hemi-Parkinsonian rats can also attenuate the β-oscillations and reduce the appearance of HVSs, as well as reverse the amphetamine-induced rotation, which is a characteristic movement of these rats. Here, we investigate how STN-HFS influences the neural activity in the motor cortex. During the interval between two consecutive stimulations, evoked LFPs corresponding to antidromic spikes and local activities are recorded in layer II/III and layer Vb regions of the M1. Local application of CNQX and bicuculline, which respectively inhibit fast glutamatergic and GABAergic synaptic transmission, in layer II/III, but not layer V of M1 greatly reduces the local activity, but not the activity corresponding to antidromic spikes induced by STN-HFS to the same side. c-Fos expression in neurons is used as an indicator of neural activity. We find that the motor cortices in the two hemispheres of hemi-Parkinsonian rats contain unequal number of c-Fos+-cells, and STN-HFS rectifies this bilateral imbalance. In addition, STN-HFS leads to the intense c-Fos expression of a group of motor cortex neurons which exhibit biochemical and anatomical characteristics resembling those of pyramidal tract (PT) neurons sending efferent projections to the STN. The number of PT neurons whith high levels of c-Fos expression is significantly reduced by local application of the antagonists to non-NMDA glutamate receptors, GABAA receptors and dopamine receptors in the upper layers of the motor cortex. The results suggest that the coincident activations of synapses and dopamine receptors in the motor cortex during STN-HFS may underlie the intense expression of c-Fos, which reflects the status of neuronal activity, of PT neurons. How dopamine receptors in the motor cortex are activated during STN-HFS and how dopamine receptor activation in the motor cortex may contribute to the therapeutic effects of STN-DBS in treating PD have also been discussed.