Abstract:

Objective To investigate the effect of mediodorsal thalamic nucleus（MD） lesions on the electrical activity of the pyramidal neurons in the medial prefrontal cortex （mPFC） of the rats with Parkinson’s disease（PD）， and to clarify the role of MD in the pathophysiological process of PD. Methods The rat model of PD was established by injecting 6-hydroxydopamine（6-OHDA） into the substantia nigra pars compacta （SNc） of the rats，and MD was damaged by intracerebral injection of ibotenic acid（IBO）. A total of 24 male SD rats were divided into normal group， SNc lesion group （PD model group）， MD lesion group （injected with IBO in MD）， and SNc+MD combined lesion group （ipsilateral MD lesion 1 week after SNc lesion），and there were 6 rats in each group. The numbers of dopamine-positive neurons in SNc and ventral tegmental area（VTA） of the rats in various groups were detected by tyrosine hydroxylase immunohistochemical staining，and Nissl staining was used to determine the location of the electrophysiological recording points and extent of the MD lesion. The firing frequencies and coefficients of variation of average interspike interval（ISI），and discharge patterns of pyramidal neurons in mPFC of the rats in various groups were observed. Results After injection with 6-OHDA， the dopamine neurons in the damaged SNc of the rats in PD model was completely disappeared， and the number of dopaminergic neurons in ipsilateral VTA in the contralateral side was significantly decreased （P<0.01）； compared with normal group， the firing frequency of mPFC pyramidal neurons of the rats in SNc lesion group was significantly increased （P<0.05）， the firing pattern tended to bursting activity （P=0.001）， and the coefficient of variation of average ISI was increased （P<0.01）； two weeks after MD lesion， the firing frequency of mPFC pyramidal neurons of the rats in SNc lesion group was significantly higher than that in normal group （P<0.01）， the bursting firing was increased （P<0.01）， and the coefficient of variation of average ISI was increased （P<0.01）；compared with normal group，the firing frequency of mPFC pyramidal neurons of the rats in SNc+MD combined lesion group had no significant difference（P>0.05），the bursting firing was increased （P<0.01）， and the coefficient of variation of avarage ISI was increased （P<0.01）. Conclusion MD plays an important role in regulating the activity of mPFC neurons， and the change of MD function may be one of the important reasons for the change of mPFC neural activity in the pathophysiological process of PD.

Key words: Parkinson’s disease, Medial prefrontal cortex, Pyramidal neuron, Mediodorsal thalamic nucleus, Electrophysiology