Lesions of mediodorsal thalamic nucleus reverse abnormal firing of the medial prefrontal cortex neurons in parkinsonian rats

Abstract

The dysfunction of the medial prefrontal cortex is associated with affective disorders and non-motor features in Parkinson’s disease. However, the exact role of the mediodorsal thalamic nucleus in the function of the prefrontal cortex remains unclear. To study the possible effects of the mediodorsal thalamic nucleus on the neurological function of the medial prefrontal cortex, a model of Parkinson’s disease was established by injecting 8 µg 6-hydroxydopamine into the substantia nigra compacta of rats. After 1 or 3 weeks, 0.3 µg ibotenic acid was injected into the mediodorsal thalamic nucleus of the midbrain. At 3 or 5 weeks after the initial injury, neuronal discharge in medial prefrontal cortex of rat brain was determined electrophysiologically. The numbers of dopamine-positive neurons and tyrosine hydroxylase immunoreactivity in substantia nigra compacta and ventral tegmental area were detected by immunohistochemical staining. Results demonstrated that after injury, the immunoreactivity of dopamine neurons and tyrosine hydroxylase decreased in the substantia nigra compacta and ventral tegmental areas of rats. Compared with normal medial prefrontal cortical neurons, at 3 and 5 weeks after substantia nigra compacta injury, the discharge frequency of pyramidal neurons increased and the discharge pattern of these neurons tended to be a burst-discharge, with an increased discharge interval. The discharge frequency of interneurons decreased and the discharge pattern also tended to be a burst-discharge, but the discharge interval was only higher at 3 weeks. At 3 weeks after the combined lesions, the discharge frequency, discharge pattern and discharge interval were restored to a normal level in pyramidal neurons and interneurons in medial prefrontal cortex. These findings have confirmed that mediodorsal thalamic nucleus is involved in regulating neuronal activities of the medial prefrontal cortex. The changes in the function of the mediodorsal thalamic nucleus may be associated with the abnormal discharge activity of the medial prefrontal cortex neurons after substantia nigra compacta injury. All experimental procedures were approved by the Institutional Animal Care and Use Committee of Xi’an Jiaotong University, China (approval No. XJTULAC2017-067) on August 26, 2017.

Keywords

• nerve regeneration; Parkinson′s disease; mediodorsal thalamic nucleus; medial prefrontal cortex; pyramidal neurons; interneurons; discharge; neural regeneration