Center for Neuroscience, University of California, Davis, Davis, CA 95618, USA.
Center for Neuroscience, University of California, Davis, Davis, CA 95618, USA.
Cell Rep. 2021 Jan 26;34(4):108664. doi: 10.1016/j.celrep.2020.108664.
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 Ca influx is sufficient to drive CaMKII-dependent long-term spine growth, even when Ca is artificially driven through voltage-gated Ca channels. Our results support a model in which non-ionotropic NMDAR signaling gates the bidirectional spine structural changes vital for brain plasticity.
经验依赖性的神经元连接的精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）信号对于长期树突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），其在长时程抑制（LTD）和棘突收缩中的非离子型 NMDAR 信号的下游，阻断长时程增强（LTP）诱导的棘突生长，但不阻断 LTP。我们假设非离子型 NMDAR 信号驱动支持双向棘突结构可塑性的细胞骨架变化。事实上，我们发现，非离子型 NMDAR 功能在 LTD 诱导的棘突收缩中的关键信号成分也对于 LTP 诱导的棘突生长是必需的。此外，具有伴随 Ca 流入的 NMDAR 构象信号足以驱动 CaMKII 依赖性长期棘突生长，即使 Ca 通过电压门控 Ca 通道被人为驱动。我们的结果支持这样一种模型，即非离子型 NMDAR 信号门控对于大脑可塑性至关重要的双向棘突结构变化。
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