Dipartimento di Biologia e Biotecnologie, Università degli Studi di Roma La Sapienza, Rome, Italy.
Neuropsychopharmacology. 2012 Apr;37(5):1122-33. doi: 10.1038/npp.2011.296. Epub 2012 Jan 4.
The ventral striatum (VS) is characterized by a distinctive neural architecture in which multiple corticolimbic glutamatergic (GLUergic) and mesolimbic dopaminergic (DAergic) afferents converge on the same output cell type (the medium-sized spiny neuron, MSN). However, despite the gateway function attributed to VS and its involvement in action selection and spatial navigation, as well as the evidence of physical and functional receptor-receptor interaction between different members of ionotropic GLUergic and DAergic receptors, there is no available knowledge that such reciprocal interaction may be critical in shaping the ability to learn novel spatial and non-spatial arrangement of stimuli. In this study, it was evaluated whether intra-VS bilateral infusion of either N-methyl-D-aspartate (NMDA) or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-selective antagonists may suppress the ability to detect spatial or non-spatial novelty in a non-associative behavioral task. In a second set of experiments, we further examined the hypothesis that VS-mediated spatial information processing may be subserved by some preferential receptor-receptor interactions among specific GLUergic and DAergic receptor subtypes. This was assessed by concomitant intra-VS infusion of the combination between subthreshold doses of either NMDA or AMPA receptor antagonists with individual D1 or D2 receptor blockade. The results of this study highlighted the fact that NMDA or AMPA receptors are differentially involved in processing of spatial and non-spatial novelty, and showed for the first time that preferential NMDA/D1 and AMPA/D2 receptor-receptor functional communication, but not NMDA/D2 and AMPA/D1, is required for enabling learning of novel spatial information in the VS.
腹侧纹状体（VS）的特征是具有独特的神经结构，其中多个皮质边缘谷氨酸能（GLUergic）和中脑边缘多巴胺能（DAergic）传入纤维汇聚到相同的输出细胞类型（中型棘神经元，MSN）。然而，尽管 VS 被认为具有门户功能，并参与了动作选择和空间导航，以及存在物理和功能受体-受体相互作用的证据，涉及不同离子型 GLUergic 和 DAergic 受体成员之间，但目前尚无知识表明这种相互作用可能对塑造学习新的空间和非空间刺激排列的能力至关重要。在这项研究中，评估了 VS 内双侧输注 N-甲基-D-天冬氨酸（NMDA）或α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体选择性拮抗剂是否会抑制在非联想行为任务中检测空间或非空间新奇性的能力。在第二组实验中，我们进一步检验了假设，即 VS 介导的空间信息处理可能由特定 GLUergic 和 DAergic 受体亚型之间的一些优先受体-受体相互作用来支持。这是通过在 VS 内同时输注亚阈值剂量的 NMDA 或 AMPA 受体拮抗剂与单独的 D1 或 D2 受体阻断剂来评估的。这项研究的结果强调了 NMDA 或 AMPA 受体在处理空间和非空间新奇性方面存在差异的事实，并首次表明，优先的 NMDA/D1 和 AMPA/D2 受体-受体功能通讯，而不是 NMDA/D2 和 AMPA/D1，对于在 VS 中学习新的空间信息是必需的。
