Mechanisms underlying pathological oscillations in the rat 6- hydroxydopamine model of Parkinson?s disease

ESCANDE MV; ZOLD CL; RIQUELME LA; BELFORTE J; MURER MG

Congreso; 14th International Congress of Parkinson?s Disease and Movement Disorders; 2010

Objective: To establish the roles of the indirect and hyperdirect pathways in the genesis of pathological oscillations in rats with nigrostriatal lesion. Background: The globus pallidus and subthalamic nucleus (STN) show increased oscillatory activity spanning a broad range of frequencies in patients with Parkinson?s disease. This increased oscillatory activity is also present in rats with nigrostriatal lesion induced by 6-hydroxydopamine (6-OHDA), a widespread model of Parkinson?s disease. Both in humans and rats, the enhanced basal ganglia oscillations are synchronized with cortical oscillations. Although there are several studies exploring the correlation with clinical signs and dopamine dependence of parkinsonian oscillatory activity, the mechanisms underlying it remain obscure. Methods: Recordings were performed in control rats and rats with nigrostriatal lesion showing motor deficiencies reminiscent of parkinsonian akinesia, under urethane anesthesia. In one set of experiments we explored the effect of blocking striatal NMDA receptors with the competitive antagonist AP-5 (100-200 lM) on oscillatory activity in the external globus pallidus (GPe). In another set we studied the short latency (presumably monosynaptic) response of STN neurons to cortical stimulation. GPe spiking activity was recorded with 16 channel silicon probes, STN activity with glass microelectrodes allowing juxtacellular labeling. In all experiments we also recorded the frontal cortex local field potential. Results: In control rats, GPe activity was not modified by intrastriatal AP-5 administration. However, the abnormal synchronization between GPe and cortical oscillations (Zold et al., 2007) as estimated by coherence analysis, was reduced by 80% during intrastriatal AP-5 administration in rats with nigrostriatal lesion (p