Long-term potentiation of the responses to parallel fiber stimulation in mouse cerebellar cortex in vivo.
Long-term potentiation of the responses to parallel fiber stimulation in mouse cerebellar cortex in vivo.
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DOI：
10.1016/j.neuroscience.2009.01.071
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发表时间：
2009-09-01
期刊：
影响因子：
3.3
通讯作者：
Ebner T
中科院分区：
文献类型：
--
作者：
Wang X;Chen G;Gao W;Ebner T
小脑中平行纤维-浦肯野细胞(PF-PC)突触的长时程增强(LTP)被认为是运动学习的基础。以前的体外研究主要使用低频PF刺激条件范式来产生突触前的PF-PC LTP(4-8 Hz)或突触后的PF-PC LTP(1 Hz)。在活体内诱发PF-PC LTP的条件知之甚少。体内高频刺激增加了PC对外周刺激的反应性；然而，无论是作用部位还是涉及的信号通路都没有得到研究。本文用黄素蛋白在活体FVB小鼠体内的自发荧光光学成像方法，描述了高频脉冲刺激(100赫兹，每3个S 15个脉冲串，持续5分钟)可引起对PF刺激反应的长期增加。在条件刺激后，对PF刺激的反应在20min内增加到∼的130%，并且这种增强持续至少2小时，对PF刺激反应的场电位记录表明，突触后成分被增强，而突触前平行纤维群不被增强。成对脉冲易化在条件性刺激后没有改变，提示这种增强发生在突触后。在条件性刺激过程中，用DNQX(6，7-二硝基-2，3-二酮二钠，50μM)阻断非N-甲基-d-天冬氨酸离子型谷氨酸受体，对长期荧光增强无影响。然而，在条件性刺激过程中，用LY367385(200μM)阻断I型代谢型谷氨酸受体(MGluR1)，可取消这种长期的荧光增强效应。阻断GABA能神经传递并不是唤起这种长期增强所必需的。阻断GABAA受体可以减少但不能消除长时程增强。因此，本研究证明在活体内高频刺激PF-PC突触可产生长时程增强效应。这种新形式的LTP主要是在突触后产生的，并由mGluR1受体介导。
Long-term potentiation (LTP) of parallel fiber–Purkinje cell (PF–PC) synapses in the cerebellum has been suggested to underlie aspects of motor learning. Previous in vitro studies have primarily used low frequency PF stimulation conditioning paradigms to generate either presynaptic PF–PC LTP (4–8 Hz) or postsynaptic PF–PC LTP (1 Hz). Little is known about the conditions that evoke PF–PC LTP in vivo. High frequency stimulation in vivo increases PC responsiveness to peripheral stimuli; however, neither the site of action nor the signaling pathways involved have been examined. Using flavoprotein autofluorescence optical imaging in the FVB mouse in vivo, this report describes that a conditioning stimulation consisting of a high frequency burst of PF stimulation (100 Hz, 15 pulse trains every 3 s for 5 min) evokes a long-term increase in the response to PF stimulation. Following the conditioning stimulation, the response to PF stimulation increases over 20 min to ∼130% above baseline and this potentiation persists for at least 2 h. Field potential recordings of the responses to PF stimulation show that the postsynaptic component is potentiated but the presynaptic, parallel fiber volley is not. Paired-pulse facilitation does not change after the conditioning stimulation, suggesting the potentiation occurs postsynaptically. Blocking non-NMDA (N-methyl-d-aspartic acid) ionotropic glutamate receptors with DNQX (6,7-dinitroquinoxaline-2,3-dione disodium salt, 50 μM, bath application) during the conditioning stimulation has no effect on the long-term increase in fluorescence. However, blocking subtype I metabotropic glutamate receptors (mGLuR1) with LY367385 (200 μM) during the conditioning stimulation abolishes the long-term increase in fluorescence. Blocking GABAergic neurotransmission is not required to evoke this long-term potentiation. Blocking GABAA receptors reduces but does not eliminate the long-term potentiation. Therefore, this study demonstrates that high frequency PF stimulation generates long-term potentiation of PF–PC synapses in vivo. This novel form of LTP is generated primarily postsynaptically and is mediated by mGluR1 receptors.
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