School of Psychology, Faculty of Science, University of New South Wales, Sydney, Australia.
School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, Australia.
Sci Adv. 2023 Jun 23;9(25):eade8247. doi: 10.1126/sciadv.ade8247.
The loss of neurons in parafascicular thalamus (Pf) and their inputs to dorsomedial striatum (DMS) in Lewy body disease (LBD) and Parkinson's disease dementia (PDD) have been linked to the effects of neuroinflammation. We found that, in rats, these inputs were necessary for both the function of striatal cholinergic interneurons (CINs) and the flexible encoding of the action-outcome (AO) associations necessary for goal-directed action, producing a burst-pause pattern of CIN firing but only during the remapping elicited by a shift in AO contingency. Neuroinflammation in the Pf abolished these changes in CIN activity and goal-directed control after the shift in contingency. However, both effects were rescued by either the peripheral or the intra-DMS administration of selegiline, a monoamine oxidase B inhibitor that we found also enhances adenosine triphosphatase activity in CINs. These findings suggest a potential treatment for the cognitive deficits associated with neuroinflammation affecting the function of the Pf and related structures.
在路易体病（LBD）和帕金森病痴呆（PDD）中，丘旁核（Pf）神经元的丢失及其对背内侧纹状体（DMS）的输入与神经炎症的影响有关。我们发现，在大鼠中，这些输入对于纹状体内胆碱能中间神经元（CIN）的功能和目标导向动作所需的动作-结果（AO）关联的灵活编码都是必要的，从而产生 CIN 放电的爆发-暂停模式，但仅在 AO 关联变化引起的重映射期间出现。Pf 中的神经炎症消除了在关联变化后 CIN 活动和目标导向控制的这些变化。然而，外周或 DMS 内给予单胺氧化酶 B 抑制剂司来吉兰均可挽救这两种作用，我们发现司来吉兰还可以增强 CIN 中的三磷酸腺苷酶活性。这些发现为治疗影响 Pf 和相关结构功能的神经炎症相关认知缺陷提供了一种潜在方法。
