Enhanced visual responses in the superior colliculus and subthalamic nucleus in an animal model of Parkinson's disease

Abstract

Striatal dopaminergic denervation leads to a change in afferent activity within the basal ganglia. Coupled with the effect of local dopaminergic denervation in the subthalamic nucleus, this is likely to affect the responsiveness of subthalamic neurons to their hyperdirect inputs in Parkinson's disease. Therefore, in this report, we investigated subthalamic nucleus responses to visual stimuli relayed by one such input - the superior colliculus - in 6-hydroxydopamine (6-OHDA)-lesioned rats. We used a protocol where the superior colliculus was selectively unlocked from the inhibitory effect of anesthesia with an injection of bicuculline, attenuating GABAergic inhibition in the colliculus, which arises predominantly from the substantia nigra pars reticulata. We found that visual responses in the superior colliculus were facilitated by partial or total lesions of dopaminergic neurons in the substantia nigra pars compacta, once the colliculus was disinhibited by bicuculline. Responses were faster, larger in amplitude and lasted longer compared to those in control rats. In the subthalamic nucleus, visual responses were also increased in amplitude and magnitude in partial or total lesioned groups. A classic hypothesis in Parkinson's disease suggests that following dopaminergic denervation, the discharge of cells in the substantia nigra pars reticulata increases, thereby intensifying the inhibitory influence that this structure exerts on its targets in the thalamus and brainstem. Our results suggest that neuroadaptations may have taken place within the superior colliculus in order to maintain normal function in the face of increased inhibitory tone coming from the substantia nigra pars reticulata, which once reduced, gave rise to facilitated responding. This facilitated responding in the superior colliculus then appears to lead to facilitated responding in the subthalamic nucleus.

Keywords: 1 - méthyle 4 - phényl 1,2,3,6-tétrahydro pyridine; 6-OHDA; 6-OHDA lesion; 6-hydroxydopamine; ANOVA; AP; BG; BSA; CONT; DA; DAB; DV; FLI; LED; ML; MPTP; NGS; NHS; NMDA; PART; PB; PD; PSTHs; Parkinson’s disease; SC; SEM; SNc; SNr; STN; TH; TOT; TX; acide N-méthyl-D-aspartique; analysis of variance; antero-posteriority; basal ganglia; bovine serum albumin; control; diaminobenzidine; dopamine; dorso-ventral; fos-like inmmunoreactivity; light-emitting diode; medio-laterality; normal goat serum; normal horse serum; partial; peristimulus time interval histograms; phosphate buffer; standard error of the mean; substantia nigra pars compacta; substantia nigra pars reticulata; subthalamic nucleus; superior colliculus; thyrosine hydroxylase; total; triton X-100.