Therapeutic Deep Brain Stimulation in Parkinsonian Rats Directly Influences Motor Cortex

• Published in: Neuron (Cambridge, Mass.) Vol. 76; no. 5; pp. 1030 - 1041
• Main Authors: Li, Qian, Ke, Ya, Chan, Danny C.W., Qian, Zhong-Ming, Yung, Ken K.L., Ko, Ho, Arbuthnott, Gordon W., Yung, Wing-Ho
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06.12.2012; Elsevier Limited
• Subjects: Action Potentials - physiology; Adrenergic Agents - toxicity; Afferent Pathways - physiology; Animals; Antiparkinson Agents - therapeutic use; Apomorphine - therapeutic use; Basal ganglia; Biophysics; Brain Mapping; Brain research; Central nervous system diseases; Cortex (motor); Deep brain stimulation; Deep Brain Stimulation - methods; Disease Models, Animal; Dominance; Dopamine; EEG; Electrical stimuli; Electrodes; Electrodes, Implanted; Electroencephalography; Electrophysiological recording; Eusebio; Evoked Potentials, Motor - physiology; Experiments; Firing pattern; Fourier transforms; Functional Laterality; Globus pallidus; Locomotion - physiology; Male; Medial Forebrain Bundle - drug effects; Medial Forebrain Bundle - physiopathology; Motor Cortex - pathology; Motor Cortex - physiopathology; Motor task performance; Movement disorders; Neurons; Neurons - drug effects; Neurons - physiology; Oscillations; Oxidopamine - toxicity; Parkinson's disease; Parkinsonian Disorders - chemically induced; Parkinsonian Disorders - physiopathology; Parkinsonian Disorders - therapy; Rats; Rats, Sprague-Dawley; Rhythms; Rodents; Solitary tract nucleus; Statistics as Topic; Stochasticity; Studies; subthalamic nucleus; Subthalamic Nucleus - physiology
• ISSN: 0896-6273; 1097-4199; 1097-4199
• DOI: 10.1016/j.neuron.2012.09.032

Much recent discussion about the origin of Parkinsonian symptoms has centered around the idea that they arise with the increase of beta frequency waves in the EEG. This activity may be closely related to an oscillation between subthalamic nucleus (STN) and globus pallidus. Since STN is the target of deep brain stimulation, it had been assumed that its action is on the nucleus itself. By means of simultaneous recordings of the firing activities from populations of neurons and the local field potentials in the motor cortex of freely moving Parkinsonian rats, this study casts doubt on this assumption. Instead, we found evidence that the corrective action is upon the cortex, where stochastic antidromic spikes originating from the STN directly modify the firing probability of the corticofugal projection neurons, destroy the dominance of beta rhythm, and thus restore motor control to the subjects, be they patients or rodents. ► First simultaneous DBS and multiunit neuronal recordings in freely moving PD rats ► Details the pathological motor cortical activities following dopamine depletion ► Unequivocal identification of antidromic spikes during deep brain stimulation ► Provides a mechanism to explain therapeutic efficacy of deep brain stimulation Based on multielectrode recordings from freely behaving Parkinsonian rats, the study by Li et al. reveals a novel mechanism of therapeutic deep brain stimulation in Parkinson’s disease.