Abstract
Parkinson’s disease is one of the most common neurodegeneration. PD patients usually experience motor symptoms associated with pathological losses of the dopaminergic neurons in substantia nigra (SN). SNc dopaminergic neuron degeneration break the balance of basal ganglia system which plays important functions in controlling movements. High frequency deep brain stimulation (DBS) is mainly used in treating the movement abnormalities of severe Parkinson's patients. STN can also effectively inhibit the abnormal neurophysiological activity (beta oscillation) in primary motor cortex (M1) observed in PD patients and animal models of PD. Earlier studies have indicated that STN-DBS may send antidromic activities to the motor cortex via the hyperdirect pathway, thereby affecting the physiological signals in M1 neural circuits. In an earlier study of our laboratory, STN-DBS has been found to induce M1 layer 5b neurons to express intensely c-Fos protein (giant c-Fos) in hemi-Parkinsonian rats. The intense c-Fos expression is these motor cortex neurons could be blocked by local application of dopamine receptor antagonist in M1. This observation suggests that STN-DBS activates motor cortex not only through antidromic pathway, but DBS also induce dopamine receptor activation in the motor cortex. In addition to substantial nigra pars compacta, ventral tegmental area (VTA) is also an important source of dopamine of motor cortex via the mesocortical pathway. Clinically, loses of dopaminergic neurons in VTA area have also been reported. The VTA resides near STN, and VTA receive STN projection. Therefore, we speculate that STN-DBS may stimulate VTA dopaminergic neurons and result in releave of dopamine in the motor cortex. The aim of my thesis is to investigate whether VTA mesocortical pathway is involved in the inhibition M1 abnormal beta-oscillation by STN-DBS. First, I confirmed that the dompaminergic neurons in theVTA was depleted by 6-OHDA injection in hemi-Parkinsonian rats. My quantitative analyses by tyrosine hydroxylase (TH) staining indicated that in the VTA, DA neurons in the lesioned side were reduced to ~25% of that in the intact side. I further investigated whether the STN-DBS inducedinhibition of the abnormal beta-oscillation in M1 layer 5b by directly stimulating the VTA. The results indicate that direct sitmulation of VTA did not affect the beta-oscillations recorded in the motor cortex of hemi-Parkinsonian rats. Coupling VTA stimulation with STN-DBS did not affect the STN-DBS-induced inhibition of beta-oscillations recorded in the motor cortex, either. However, it remains unclear if direct stimulation of VTA affects the STN-DBS effects on the behavioral abnormalities associated with PD.