Non-ionotropic NMDA receptor signaling gates bidirectional structural plasticity of dendritic spines.
Non-ionotropic NMDA receptor signaling gates bidirectional structural plasticity of dendritic spines.
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DOI：
10.1016/j.celrep.2020.108664
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发表时间：
2021-01-26
期刊：
影响因子：
8.8
通讯作者：
Zito K
中科院分区：
文献类型：
--
作者：
Stein IS;Park DK;Claiborne N;Zito K
神经元连接的经验依赖性细化对于大脑发育和学习至关重要。在这里，我们表明离子流非依赖性NMDA受体（NMDAR）信号传导是长期树枝状棘生长所需的，而树枝状棘生长是脑回路可塑性的重要组成部分。我们发现，抑制p38丝裂原活化蛋白激酶（p38 MAPK），这是下游的非离子型NMDAR信号在长时程抑郁症（LTD）和脊柱收缩，阻断长时程增强（LTP）诱导的脊柱生长，但不是LTP。我们推测，非离子型NMDAR信号驱动细胞骨架的变化，支持双向脊柱结构可塑性。事实上，我们发现，关键的信号组件下游的非离子型NMDAR功能在LTD诱导的脊柱收缩也是必要的LTP诱导的脊柱生长。此外，NMDAR构象信号与一致的Ca2+内流足以驱动CaMKII依赖性的长期脊柱生长，即使当Ca2+通过电压门控Ca2+通道人工驱动时。我们的研究结果支持了一个模型，其中非离子型NMDAR信号门的双向脊柱结构的变化至关重要的大脑可塑性。树突棘的结构可塑性是学习过程中脑回路重塑的关键步骤。Stein等人证明了离子通量无关的NMDAR信号在可塑性相关的树突棘生长中的重要作用，支持了非离子型NMDAR信号引发棘肌动蛋白细胞骨架双向结构可塑性的模型。
Experience-dependent refinement of neuronal connections is critically important for brain development and learning. Here, we show that ion-flow-independent NMDA receptor (NMDAR) signaling is required for the long-term dendritic spine growth that is a vital component of brain circuit plasticity. We find that inhibition of p38 mitogen-activated protein kinase (p38 MAPK), which is downstream of non-ionotropic NMDAR signaling in long-term depression (LTD) and spine shrinkage, blocks long-term potentiation (LTP)-induced spine growth but not LTP. We hypothesize that non-ionotropic NMDAR signaling drives the cytoskeletal changes that support bidirectional spine structural plasticity. Indeed, we find that key signaling components downstream of non-ionotropic NMDAR function in LTD-induced spine shrinkage are also necessary for LTP-induced spine growth. Furthermore, NMDAR conformational signaling with coincident Ca2+ influx is sufficient to drive CaMKII-dependent long-term spine growth, even when Ca2+ is artificially driven through voltage-gated Ca2+ channels. Our results support a model in which non-ionotropic NMDAR signaling gates the bidirectional spine structural changes vital for brain plasticity. Structural plasticity of dendritic spines is a critical step in the remodeling of brain circuits during learning. Stein et al. demonstrate a vital role for ion-flux-independent NMDAR signaling in plasticity-associated dendritic spine growth, supporting a model in which non-ionotropic NMDAR signaling primes the spine actin cytoskeleton for bidirectional structural plasticity.
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DOI：
10.1073/pnas.1520023112
发表时间：
2015-11-24
影响因子：
11.1
作者：
Dore, Kim;Aow, Jonathan;Malinow, Roberto
通讯作者：
Malinow, Roberto
影响因子：
64.8
作者：
Hayashi-Takagi A;Yagishita S;Nakamura M;Shirai F;Wu YI;Loshbaugh AL;Kuhlman B;Hahn KM;Kasai H
通讯作者：
Kasai H
影响因子：
16.2
作者：
Bosch M;Castro J;Saneyoshi T;Matsuno H;Sur M;Hayashi Y
通讯作者：
Hayashi Y
影响因子：
64.8
作者：
Hedrick NG;Harward SC;Hall CE;Murakoshi H;McNamara JO;Yasuda R
通讯作者：
Yasuda R
影响因子：
25
作者：
Hayama, Tatsuya;Noguchi, Jun;Watanabe, Satoshi;Takahashi, Noriko;Hayashi-Takagi, Akiko;Ellis-Davies, Graham C. R.;Matsuzaki, Masanori;Kasai, Haruo
通讯作者：
Kasai, Haruo