A basal ganglia pacemaker formed by the subthalamic nucleus and external globus pallidus

The subthalamic nucleus of the basal ganglia (STN) is important for normal movement(1,2) as well as in movement disorders(3-5). Lesioning(6) or deep-brain stimulation(7,8) of the STN can alleviate resting tremor in Parkinson's disease. The STN5 and its target nuclei(9,10) display synchronized oscillatory burst discharge at low frequencies, some of which correlate with tremor, but the mechanism underlying this synchronized bursting is unknown. Here we show that the excitatory STN and inhibitory, external globus pallidus (GPe) form a feedback system that engages in synchronized bursting. In mature organotypic cortex-striatum-STN-GPe cultures, neurons in the STN and GPe spontaneously produce synchronized oscillating bursts at 0.4, 0.8 and 1.8 Hz. Pallidal lesion abolishes this bursting, whereas cortical lesion favours bursting at 0.8 Hz. Pallidal bursts, although weaker than STN bursts, were required for synchronized oscillatory burst generation by recruitment of subthalmic rebound excitation. We propose that the STN and GPe constitute a central pacemaker modulated by striatal inhibition of GPe neurons. This pacemaker could be responsible for synchronized oscillatory activity in the normal and pathological basal ganglia.