On the relationships between the caudal intralaminar nuclei of the thalamus and the basal ganglia : implications for the pathophysiology of Parkinson’s disease

Abstract

Besides corticostriatal projections, the thalamic intralaminar nuclei are a major source of glutamatergic afferents reaching the basal ganglia input nuclei. Although the thalamostriatal system is already well characterized from the anatomical point of view, the role to be played by this pathway within basal ganglia function (both in normal and pathological conditions) remains poorly understood. On one hand, neurode- generation phenomena restricted to the caudal intralaminar nuclei have been described in several neurodegenerative disorders such as Parkinson’s disease, progressive supranuclear palsy and Huntington’s disease. On the other hand, after unilateral dopaminergic depletion in rodents the caudal intralaminar nuclei are highly hyperactive. Indeed, the chemical ablation of the caudal intralaminar nuclei prevents the increase of the activity observed in both the basal ganglia output nuclei and the subthalamic nucleus (STN) after unilateral dopaminergic depletion. These findings suggest that the caudal intralaminar nuclei might be responsible (at least partially) for the changes in activity of the STN and basal ganglia output nuclei typically seen under circumstances of dopamine removal. These results paved the way for the implementation of pioneer clinical experiences focused on targeting the caudal intralaminar nuclei with a deep brain stimulation electrode in patients suffering from advanced Parkinson’s disease. This approach resulted in the alleviation of cardinal symptoms of the disease such as resting tremor, druginduced dyskinesias and chronic pain.