Target cell-specific plasticity rules of NMDA receptor-mediated synaptic transmission in the hippocampus.
Target cell-specific plasticity rules of NMDA receptor-mediated synaptic transmission in the hippocampus.
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DOI：
10.3389/fncel.2023.1068472
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发表时间：
2023
影响因子：
5.3
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中科院分区：
文献类型：
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NMDA受体介导的突触传递的长时程增强和抑制（NMDAR LTP/LTD）可以显著影响多个脑区的突触功能和信息传递。然而，决定NMDAR可塑性方向的机制知之甚少。在这里，使用突触前和突触后爆发活动，全细胞膜片钳记录，2-光子激光钙成像在急性大鼠海马切片和免疫电子显微镜的生理相关模式，我们测试是否不同的钙动力学和I组代谢型谷氨酸受体（I-mGluR）亚型控制NMDAR可塑性的迹象。我们发现，突触后钙瞬变（CaTs）在海马MF刺激显着更大的诱导过程中的NMDAR-LTP相比，NMDAR-LTD在MF-CA 3锥体细胞（MF-CA 3）突触。这种差异被取消的药理学阻断mGluR 5和细胞内钙库的耗竭显着减少，而阻断mGluR 1对这些钙没有影响。此外，我们还发现MF到门苔藓细胞（MF-MC）突触与MF-CA 3突触在结构和功能上有一些共同点，也经历了NMDAR可塑性。然而，令我们惊讶的是，我们发现在这两个突触处I-mGluR亚型的突触后分布不同，并且在MF-CA 3突触处诱导NMDAR-LTD的相同诱导方案仅在MF-MC突触处触发NMDAR-LTP，尽管钙动力学相当。因此，单独的突触后钙动力学不能预测NMDAR可塑性的迹象，表明突触后钙升高和I-mGluR亚型的相对贡献可能决定NMDAR可塑性的学习规则。
Long-term potentiation and depression of NMDA receptor-mediated synaptic transmission (NMDAR LTP/LTD) can significantly impact synapse function and information transfer in several brain areas. However, the mechanisms that determine the direction of NMDAR plasticity are poorly understood. Here, using physiologically relevant patterns of presynaptic and postsynaptic burst activities, whole-cell patch clamp recordings, 2-photon laser calcium imaging in acute rat hippocampal slices and immunoelectron microscopy, we tested whether distinct calcium dynamics and group I metabotropic glutamate receptor (I-mGluR) subtypes control the sign of NMDAR plasticity. We found that postsynaptic calcium transients (CaTs) in response to hippocampal MF stimulation were significantly larger during the induction of NMDAR-LTP compared to NMDAR-LTD at the MF-to-CA3 pyramidal cell (MF-CA3) synapse. This difference was abolished by pharmacological blockade of mGluR5 and was significantly reduced by depletion of intracellular calcium stores, whereas blocking mGluR1 had no effect on these CaTs. In addition, we discovered that MF to hilar mossy cell (MF-MC) synapses, which share several structural and functional commonalities with MF-CA3 synapses, also undergoes NMDAR plasticity. To our surprise, however, we found that the postsynaptic distribution of I-mGluR subtypes at these two synapses differ, and the same induction protocol that induces NMDAR-LTD at MF-CA3 synapses, only triggered NMDAR-LTP at MF-MC synapses, despite a comparable calcium dynamics. Thus, postsynaptic calcium dynamics alone cannot predict the sign of NMDAR plasticity, indicating that both postsynaptic calcium rise and the relative contribution of I-mGluR subtypes likely determine the learning rules of NMDAR plasticity.
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影响因子：
16.2
作者：
Danielson NB;Turi GF;Ladow M;Chavlis S;Petrantonakis PC;Poirazi P;Losonczy A
通讯作者：
Losonczy A
影响因子：
3.4
作者：
Hedrick TP;Nobis WP;Foote KM;Ishii T;Chetkovich DM;Swanson GT
通讯作者：
Swanson GT
影响因子：
16.2
作者：
Borgland, SL;Taha, SA;Bonci, A
通讯作者：
Bonci, A
影响因子：
13.8
作者：
Conn PJ;Lindsley CW;Jones CK
通讯作者：
Jones CK
影响因子：
16.2
作者：
Chalifoux JR;Carter AG
通讯作者：
Carter AG