SWITCH FROM EXCITATORY TO INHIBITORY CORTICAL CONTROL OF GP NEURONS ACTIVITY IN 6-OHDA RATS

C. ZOLD, L. RIQUELME, M.G. MURER.

Washington DC

Congreso; Society for Neuroscience Meeting; 2005

The normal operation of the basal ganglia (BG) requires the processing of cortical information through segregated parallel channels along with the integration of cortical-striatal and cortical-subthalamic inputs. Nigrostriatal lesions would alter essential aspects of information processing in the BG causing the clinical signs of parkinsonism.   The globus pallidus (GP) receives cortical inputs through the striatum (inhibitory) and subthalamus (excitatory). It is presumed that the striatal-pallidal neurons are under a strong inhibitory control exercised by nigrostriatal dopamine. Our hypothesis is that nigrostriatal degeneration increases the influence of the striatal-pallidal projection on GP neurons.   Both control and 6-OHDA-lesioned animals (a widespread model of parkinsonism), presented a group of neurons with low-frequency modulations coupled to slow cortical rhythm (71% vs 73% respectively). In control rats the positive phase of the ECoG slow waves (that reflects synchronized activation of a great number of cortical neurons) was accompanied by an increase of GP units firing probability. Conversely, 56% of the modulated units in the lesioned rats presented an inverse phase relation. We only found this type of relation with the ECoG in 3% of the control rats units (p<0.001).   In 6-OHDA-lesioned rats 84% (37 of 44) of GP neurons responded to motor cortex stimulation against 22% (9 of 41 neurons) in control animal (p<0.001). This increased responsiveness was due to a greater incidence of both excitations (77% vs 17%, p<0.001) and inhibitions (50% vs 9%, p<0.01).   These results indicate: i) a possible change in the dominant mechanism of cortical control on 6-OHDA-lesioned rats (cortical-subthalamus-GP control versus cortical-striatum-GP control) ii) that the representation of a focus of cortical activity is distributed more extensively in the GP in experimental parkinsonism, suggesting a degradation of the capacity of parallel processing that could be explained by an increased transfer of activity through both the cortical-striatum-GP and cortical-subthalamus-GP pathways.  Supported by UBACYT, FONCYT, CONICET