Evidence for glycinergic GluN1/GluN3 NMDA receptors in hippocampal metaplasticity.
Evidence for glycinergic GluN1/GluN3 NMDA receptors in hippocampal metaplasticity.
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海马化生中甘氨酸 GluN1/GluN3 NMDA 受体的证据。
DOI：
10.1016/j.nlm.2015.10.005
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发表时间：
2015
影响因子：
2.7
通讯作者：
Pak,DanielTS
中科院分区：
文献类型：
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作者：
Rozeboom,AaronM;Queenan,BridgetN;Partridge,JohnG;Farnham,Christina;Wu,Jian-Young;Vicini,Stefano;Pak,DanielTS
突触可塑性的Hebbian或联想形式被认为是学习和记忆的分子基础。然而，包括长时程增强（LTP）和抑制（LTD）在内的联合突触修饰可以形成正反馈回路，必须限制这些正反馈回路以使神经网络保持稳定。一种被提出的约束机制是超可塑性，即突触变化改变随后可塑性阈值的过程。亚塑性已经在功能上被观察到，但分子基础还没有很好地理解。在这里，我们报告的刺激，诱导LTP招募GluN 2B缺乏GluN 1/GluN 3 NMDA受体（NMDARs）的海马锥体神经元的兴奋性突触。这些非常规受体可能与传统的GluN 1/GluN 2 NMDAR竞争，以促进突触去增强，从而响应随后的“LTP诱导”刺激。这些结果暗示甘氨酸能GluN 1/GluN 3 NMDAR作为过度突触强化的分子制动器，表明这些受体在大脑中的作用以前一直难以捉摸。
Hebbian, or associative, forms of synaptic plasticity are considered the molecular basis of learning and memory. However, associative synaptic modifications, including long-term potentiation (LTP) and depression (LTD), can form positive feedback loops which must be constrained for neural networks to remain stable. One proposed constraint mechanism is metaplasticity, a process whereby synaptic changes shift the threshold for subsequent plasticity. Metaplasticity has been functionally observed but the molecular basis is not well understood. Here, we report that stimulation which induces LTP recruits GluN2B-lacking GluN1/GluN3 NMDA receptors (NMDARs) to excitatory synapses of hippocampal pyramidal neurons. These unconventional receptors may compete against conventional GluN1/GluN2 NMDARs to favor synaptic depotentiation in response to subsequent “LTP-inducing” stimulation. These results implicate glycinergic GluN1/GluN3 NMDAR as molecular brakes on excessive synaptic strengthening, suggesting a role for these receptors in the brain that has previously been elusive.