Abstract
Parkinson’s disease (PD) is a common neurodegenerative disease of the central nervous system. PD patients usually exhibit various motor symptoms associated with the loss of dopaminergic (DAergic) neurons in substantia nigra (SN).A present, the cause for PD is still unknown, and there is no cure for PD. High-frequency deep brain stimulation (DBS) of subthalamic nucleus (STN) is an effective and commonly used surgical procedure to treat the motor dysfunctions of severe PD patients. Nevertheless, the mechanism underlying the therapeutic effects of STN-DBS on PD is not fully understood. In this research, we used hemi-Parkinsonian rats as a model to study the mechanisms of STN-DBS. We employed c-Fos as a marker to identify the cells which were activated by STN-DBS. We noted the appearance of a group of large and strong c-Fos positive cells (called as giant c-Fos positive cells henceforth) in the layer Vb of the motor cortex ipsilateral to the lesion side (also the side where STN-DBS was applied) in hemi-PD rats. Much less giant c-Fos positive cells were however found in the motor cortices on contralateral side of PD rats or on either side of normal rats also subjected to STN-DBS. In order to characterize these giant c-Fos positive cells, we performed double fluorescence immunostaining by using the c-Fos antibody in combination with the antibody to anti-NeuN (NeuN), anti-glutamic acid decarboxylase (GAD67) or anti-Neurofilament H Non-Phosphorylated antibody (SMI32). The results indicated that giant c-Fos positive cells were primarily pyramidal tract type (PT-type) neurons, which are surrounded by GABAergic (GAD67 positive) puncta. To explore the connectivity of these giant c-Fos positive neurons, we did Fast Blue retrograde labeling. Two weeks after injecting Fast Blue in the STN, most of the giant c-Fos positive neurons in the motor cortex were also labeled by Fast blue. This observation suggests that the giant c-Fos positive neurons found in layer Vb of the motor cortex send axon collaterals to the STN. On the basis of these data, we propose that the strong activation of these PT-type neurons in layer Vb of the motor cortex by STN-DBS may be partly due to the antidromic activities from these axon collaterals. I also observed that the applications of bicuculline and CNQX in the upper layer (L1, L2/3 and L5a) of motor cortex could noticeably block the appearance of giant c-Fos expression in layer 5b after STN-DBS. We speculate that the networks of motor cortex in PD rats, especially those with synapses residing in layer 2/3, may involve in the strongly activation the giant c-Fos positive neurons during STN-DBS in PD rats. Lastly, giant c-Fos positive cells were also detected in the motor cortex of hemi-PD rats which were subjected to STN-DBS on the same side. This last observation suggests the alterations of the motor cortex on the intact side of a hemi-PD rat.