Enhanced AMPA receptor function promotes cerebellar long-term depression rather than potentiation.
Enhanced AMPA receptor function promotes cerebellar long-term depression rather than potentiation.
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DOI：
10.1101/lm.035220.114
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发表时间：
2014-12
期刊：
影响因子：
--
通讯作者：
Hansel C
中科院分区：
文献类型：
--
作者：
van Beugen BJ;Qiao X;Simmons DH;De Zeeuw CI;Hansel C
Ampakines是AMPA受体的变构调节剂，其促进海马长时程增强（LTP）和学习，并且已被考虑用于治疗认知和记忆缺陷。在这里，我们表明，安巴金CX 546提高幅度和减缓兴奋性突触后电流（EPSC）的衰减时间在小脑平行纤维（PF）浦肯野细胞突触，从而类似CX 546在海马突触的影响。使用荧光钙指示染料俄勒冈州绿色BAPTA-2和超高速CCD相机，我们还监测浦肯野细胞树突中的钙瞬变。在浴中存在CX 546的情况下，PF诱发的钙瞬变增强并延长，表明CX 546不仅增强突触传递，而且增强小脑突触处的树突状钙信号。然而，与先前在海马体中的观察相反，在小脑记录期间应用CX 546促进PF突触的长期抑郁（LTD）而不是LTP。这些发现表明，ampakines选择性地修改LTP-LTD平衡取决于脑区域和突触的类型，并可能提供工具，有针对性地调节突触记忆。
Ampakines are allosteric modulators of AMPA receptors that facilitate hippocampal long-term potentiation (LTP) and learning, and have been considered for the treatment of cognition and memory deficits. Here, we show that the ampakine CX546 raises the amplitude and slows the decay time of excitatory postsynaptic currents (EPSCs) at cerebellar parallel fiber (PF) to Purkinje cell synapses, thus resembling CX546 effects described at hippocampal synapses. Using the fluorescent calcium indicator dye Oregon Green BAPTA-2 and an ultra-high-speed CCD camera, we also monitored calcium transients in Purkinje cell dendrites. In the presence of CX546 in the bath, PF-evoked calcium transients were enhanced and prolonged, suggesting that CX546 not only enhances synaptic transmission, but also boosts dendritic calcium signaling at cerebellar synapses. In contrast to previous observations in the hippocampus, however, CX546 applied during cerebellar recordings facilitates long-term depression (LTD) rather than LTP at PF synapses. These findings show that ampakines selectively modify the LTP–LTD balance depending on the brain area and type of synapse, and may provide tools for the targeted regulation of synaptic memories.
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影响因子：
64.8
作者：
Finch, EA;Augustine, GJ
通讯作者：
Augustine, GJ
影响因子：
5.5
作者：
ITO, M;SAKURAI, M;TONGROACH, P
通讯作者：
TONGROACH, P
影响因子：
3.3
作者：
Arai, AC;Xia, YF;Suzuki, E
通讯作者：
Suzuki, E
DOI：
10.1073/pnas.92.18.8279
发表时间：
1995-08-29
影响因子：
11.1
作者：
DENK, W;SUGIMORI, M;LLINAS, R
通讯作者：
LLINAS, R
影响因子：
11.2
作者：
Coesmans, M;Smitt, PAS;De Zeeuw, CI
通讯作者：
De Zeeuw, CI