Subthalamic nucleus high-frequency stimulation generates a concomitant synaptic excitation–inhibition in substantia nigra pars reticulata

摘要

Non-technical summaryParkinson's disease, a neurodegenerative pathology, causes motor and cognitive impairments such as tremor at rest, muscle rigidity and depression. An efficient surgical therapy, deep brain stimulation, allows treatment of most symptoms of Parkinson's disease. The principle of deep brain stimulation is to stimulate electrically, at high frequency and low intensity, the subthalamic nucleus. However, how deep brain stimulation works is still not fully elucidated. We investigated the mechanism of deep brain stimulation of the subthalamic nucleus by recording the activity of neurons that are directly under the control of subthalamic nucleus neurons. We demonstrate that deep brain stimulation of the subthalamic nucleus activates local subthalamic glutamatergic neurons as well as GABAergic fibres travelling through this structure inducing a synaptic excitation–inhibition balance in the output structure. Thus, we conclude that deep brain stimulation restores the activity of the pathological brain network by providing a proper excitation–inhibition balance.