Studies of the neural mechanisms of deep brain stimulation in rodent models of Parkinson's disease.

Several rodent models of deep brain stimulation (DBS) have been developed in recent years. Electrophysiological and neurochemical studies have been performed to examine the mechanisms underlying the effects of DBS. In vitro studies have provided deep insights into the role of ion channels in response to brain stimulation. In vivo studies reveal neural responses in the context of intact neural circuits. Most importantly, recording of neural responses to behaviorally effective DBS in freely moving animals provides a direct means for examining how DBS modulates the basal ganglia thalamocortical circuits and thereby improves motor function. DBS can modulate firing rate, normalize irregular burst firing patterns and reduce low frequency oscillations associated with the Parkinsonian state. Our current efforts are focused on elucidating the mechanisms by which DBS effects on neural circuitry improve motor performance. New behavioral models and improved recording techniques will aide researchers conducting future DBS studies in a variety of behavioral modalities and enable new treatment strategies to be explored, such as closed-loop stimulations based on real time computation of ensemble neural activity.