Institut des Neurosciences de Grenoble, Dynamique et Physiopathologie des Ganglions de la Base, Centre de Recherche Inserm U.836, Site Santé La Tronche, 38042 Grenoble Cedex 9, France; Université Joseph Fourier, Grenoble, France.
Neuroscience. 2013 Nov 12;252:277-88. doi: 10.1016/j.neuroscience.2013.07.047. Epub 2013 Jul 31.
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.
纹状体多巴胺能神经末梢丧失导致基底神经节传入活动的改变。加上苍白球内局部多巴胺能神经末梢丧失的影响，这可能会影响帕金森病患者苍白球神经元对其超直接传入的反应性。因此，在本报告中，我们研究了通过超直接输入之一——上丘——传递的视觉刺激对 6-羟多巴胺（6-OHDA）损伤大鼠丘脑底核的反应。我们使用了一种方案，通过注射荷包牡丹碱选择性地解除上丘对麻醉的抑制作用，减弱上丘中的 GABA 抑制作用，这种抑制作用主要来自黑质网状部。我们发现，一旦上丘被荷包牡丹碱去抑制，黑质致密部多巴胺能神经元的部分或完全损伤会促进上丘的视觉反应。与对照组大鼠相比，反应更快、幅度更大、持续时间更长。在丘脑底核中，部分或完全损伤组的视觉反应幅度和幅度也增加。帕金森病的一个经典假设表明，多巴胺能神经末梢丧失后，黑质网状部细胞的放电增加，从而增强了该结构对丘脑和脑干靶细胞的抑制影响。我们的结果表明，在上丘中可能已经发生了神经适应，以在来自黑质网状部的抑制性张力增加的情况下维持正常功能，一旦这种张力减少，就会产生促进反应。上丘中的这种促进反应似乎导致了丘脑底核中的促进反应。
