Cerebellar mechanisms in eyeblink conditioning
Cerebellar mechanisms in eyeblink conditioning
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DOI：
10.1111/j.1749-6632.2002.tb07557.x
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发表时间：
2002-01-01
期刊：
影响因子：
--
通讯作者：
Yeo, CH
中科院分区：
文献类型：
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作者：
Attwell, PJE;Ivarsson, M;Yeo, CH
最近的眨眼调节小脑学习模型预测了两个可塑性部位：小脑皮质和小脑核，它们分别存储与计时和驱动运动相关的信息。与这个想法一致，皮层的损伤或浦肯野细胞输出到细胞核的可逆“断开”已被证明会破坏反应时间，从而产生短潜伏期的条件性眨眼。为了更好地表征潜在的皮质和核可塑性，我们分析了给予皮质和细胞核的不同药物对瞬膜（NM）和眨眼条件反应（CR）的影响。当输注 AMPA 受体拮抗剂 CNQX 或 GABA-A 受体拮抗剂印防己毒素或 SR95531 阻断小脑皮质小叶 HVI 的兴奋性或抑制性输入时，CR 被废除。同样，小脑核中的 GABA-A 受体拮抗剂消除了 CR。 CR 延迟从未缩短。然而，阻断 AMPA/红藻氨酸受体介导的细胞核兴奋性传输对 CR 频率或潜伏期没有影响。这些结果表明，NM 和眨眼 CR 的表现需要正常的皮质和核功能。我们没有看到任何证据表明 CR 可以由 AMPA/红藻氨酸受体介导的从苔藓纤维传入到小脑核的传输驱动。因此，虽然不排除小脑核的可塑性，但 AMPA 受体介导的从苔藓纤维输入到核的传输的长期变化不太可能是眨眼条件反射的重要机制。我们的研究结果表明，需要功能齐全的橄榄-皮质-核环来表达关联条件反应的所有特征。
A recent model of cerebellar learning in eyeblink conditioning predicts two sites of plasticity, the cerebellar cortex and cerebellar nuclei, which store information relating to timing and driving the movement, respectively. Consistent with this idea, lesions of the cortex or reversible "disconnections" of Purkinje cell output to the nuclei have been shown to disrupt response timing to produce short-latency conditioned eyeblinks. To better characterize potential cortical and nuclear plasticities, we analyzed the effects upon nictitating membrane (NM) and eyeblink conditioned responses (CRs) of different drugs administered to the cortex and to the nuclei. When either excitatory or inhibitory inputs to the cerebellar cortical lobule HVI were blocked by infusions of the AMPA receptor antagonist CNQX or the GABA-A receptor antagonists picrotoxin or SR95531, CRs were abolished. Similarly GABA-A receptor antagonists in the cerebellar nuclei abolished CRs. CR latencies were never shortened. However, blockade of AMPA/kainate receptor-mediated excitatory transmission to the nuclei had no effect upon CR frequencies or latencies. These results suggest that normal cortical and nuclear function is required for performance of NM and eyeblink CRs. We saw no evidence that CRs can be driven by AMPA/kainate receptor-mediated transmission from mossy fiber afferents to the cerebellar nuclei. So, although plasticity in the cerebellar nuclei is not ruled out, it is unlikely that a long-term change in AMPA receptor-mediated transmission from mossy fiber inputs to the nuclei is an essential mechanism in eyeblink conditioning. Our findings indicate that a fully functional olivo-cortico-nuclear loop is required to express all characteristics of associatively conditioned responses.