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Calcium-Permeable AMPA Receptors Mediate Timing-Dependent LTP Elicited by Low Repeat Coincident Pre- and Postsynaptic Activity at Schaffer Collateral-CA1 Synapses
Cerebral Cortex ( IF 3.7 ) Pub Date : 2021-08-09 , DOI: 10.1093/cercor/bhab306
Efrain A Cepeda-Prado 1 , Babak Khodaie 1, 2 , Gloria D Quiceno 1 , Swantje Beythien 1 , Elke Edelmann 1, 2, 3 , Volkmar Lessmann 1, 2, 3
Affiliation  

High-frequency stimulation induced long-term potentiation (LTP) and low-frequency stimulation induced LTD are considered as cellular models of memory formation. Interestingly, spike timing-dependent plasticity (STDP) can induce equally robust timing-dependent LTP (t-LTP) and t-LTD in response to low frequency repeats of coincident action potential (AP) firing in presynaptic and postsynaptic cells. Commonly, STDP paradigms relying on 25–100 repeats of coincident AP firing are used to elicit t-LTP or t-LTD, but the minimum number of repeats required for successful STDP is barely explored. However, systematic investigation of physiologically relevant low repeat STDP paradigms is of utmost importance to explain learning mechanisms in vivo. Here, we examined low repeat STDP at Schaffer collateral-CA1 synapses by pairing one presynaptic AP with either one postsynaptic AP (1:1 t-LTP), or a burst of 4 APs (1:4 t-LTP) and found 3–6 repeats to be sufficient to elicit t-LTP. 6× 1:1 t-LTP required postsynaptic Ca2+ influx via NMDARs and L-type VGCCs and was mediated by increased presynaptic glutamate release. In contrast, 1:4 t-LTP depended on postsynaptic metabotropic GluRs and ryanodine receptor signaling and was mediated by postsynaptic insertion of AMPA receptors. Unexpectedly, both 6× t-LTP variants were strictly dependent on activation of postsynaptic Ca2+-permeable AMPARs but were differentially regulated by dopamine receptor signaling. Our data show that synaptic changes induced by only 3–6 repeats of mild STDP stimulation occurring in ≤10 s can take place on time scales observed also during single trial learning.

中文翻译:

钙渗透性 AMPA 受体介导由 Schaffer Collat​​eral-CA1 突触处的低重复重合突触前和突触后活动引发的时间依赖性 LTP

高频刺激诱导的长时程增强 (LTP) 和低频刺激诱导的 LTD 被认为是记忆形成的细胞模型。有趣的是,尖峰时间依赖性可塑性 (STDP) 可以诱导同样强大的时间依赖性 LTP (t-LTP) 和 t-LTD,以响应突触前和突触后细胞中同时动作电位 (AP) 发射的低频重复。通常,依赖于 25-100 次重复同步 AP 触发的 STDP 范例用于引发 t-LTP 或 t-LTD,但几乎没有探索成功 STDP 所需的最小重复次数。然而,对生理相关的低重复 STDP 范式的系统研究对于解释体内学习机制至关重要。这里,我们通过将一个突触前 AP 与一个突触后 AP (1:1 t-LTP) 或一组 4 个 AP (1:4 t-LTP) 配对来检查 Schaffer 侧枝 CA1 突触的低重复 STDP,并发现 3-6 个重复足以引发 t-LTP。6×1:1 t-LTP 需要通过 NMDAR 和 L 型 VGCC 的突触后 Ca2+ 流入,并由突触前谷氨酸释放增加介导。相比之下,1:4 t-LTP 依赖于突触后代谢型 GluR 和兰尼碱受体信号传导,并由 AMPA 受体的突触后插入介导。出乎意料的是,两种 6×t-LTP 变体都严格依赖于突触后 Ca2+ 可渗透 AMPAR 的激活,但受多巴胺受体信号传导的不同调节。
更新日期:2021-08-09
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