INVESTIGADORES
MURER Mario Gustavo
congresos y reuniones científicas
Título:
Mechanisms underlying pathological oscillations in the rat 6- hydroxydopamine model of Parkinsons disease
Autor/es:
ESCANDE MV; ZOLD CL; RIQUELME LA; BELFORTE J; MURER MG
Lugar:
Buenos Aires
Reunión:
Congreso; 14th International Congress of Parkinsons Disease and Movement Disorders,; 2010
Institución organizadora:
Movement Disorders Vol. 25, Suppl. 2, 2010, pp. S181S189
Resumen:
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 Parkinsons disease. This increased oscillatory
activity is also present in rats with nigrostriatal lesion induced
by 6-hydroxydopamine (6-OHDA), a widespread model of Parkinsons
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