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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Cerebellar dysfunction explains the extinction-like abolition of conditioned eyeblinks after NBQX injections in the inferior olive.
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Cerebellar dysfunction explains the extinction-like abolition of conditioned eyeblinks after NBQX injections in the inferior olive.

机译：小脑功能障碍解释了在下橄榄中注射NBQX后灭绝了条件性眨眼。

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摘要

Classical conditioning of the eyeblink response is a form of motor learning that is controlled by the intermediate cerebellum and related brainstem structures. The inferior olive (IO) is commonly thought to provide the cerebellum with a teaching Testing this concept has been difficult because the IO, in addition to its putative learning function, also controls tonic activity in the cerebellum. Previously, it was reported that inactivation of AMPA/kainate receptors in the IO produces extinction of conditioned responses (CRs), suggesting that it blocks the transmission of US signals without perturbing the functional state of the cerebellum. However, the electrophysiological support for this critical finding was lacking, mostly because of methodological difficulties in maintaining stable recordings from the same set of single units throughout long drug injection sessions in awake rabbits. To address this critical issue, we used our microwire-based multiple single-unit recording method. The IO in trained rabbits was injected with the AMPA/kainate receptor blocker, 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX), and its effects on CR expression and neuronal activity in the cerebellar interposed nuclei (IN) were examined. We found that NBQX abolished CR expression and that delayed drug effects were independent of the presentation of the conditioned stimulus and were therefore not related to extinction. In parallel to these behavioral effects, the spontaneous neuronal activity and CR-related neuronal responses in the IN were suppressed, suggesting cerebellar dysfunction. These findings indicate that testing the role of IO in learning requires methods that do not alter the functional state of the cerebellum.
机译：眨眼反应的经典条件是运动学习的一种形式，由中间小脑和相关的脑干结构控制。通常认为下橄榄（IO）可为小脑提供教学。测试此概念非常困难，因为IO除了其推定的学习功能外，还控制小脑的强直活动。以前，有报道称，IO中AMPA /海藻酸酯受体的失活会导致条件反应（CR）灭绝，这表明它在不干扰小脑功能状态的情况下阻止了US信号的传递。但是，缺乏对这一关键发现的电生理支持，这主要是因为在清醒兔子的长时间药物注射过程中，难以从同一套单一装置保持稳定的记录的方法学上的困难。为了解决这个关键问题，我们使用了基于微线的多个单单元记录方法。在训练有素的兔子的IO中注射AMPA /海藻酸酯受体阻滞剂，1,2,3,4-四氢-6-硝基-2,3-二氧-苯并[f]喹喔啉-7-磺酰胺（NBQX）研究了对小脑插入核（IN）中CR表达和神经元活性的影响。我们发现NBQX废除了CR表达，并且延迟的药物作用与条件刺激的表现无关，因此与灭绝无关。在这些行为影响的同时，IN中的自发性神经元活动和CR相关的神经元反应受到抑制，提示小脑功能障碍。这些发现表明，测试IO在学习中的作用需要采用不改变小脑功能状态的方法。

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