RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
Cell Rep. 2012 May 31;1(5):495-505. doi: 10.1016/j.celrep.2012.03.007. Epub 2012 Apr 26.
Synaptic NMDA receptors (NMDARs) are crucial for neural coding and plasticity. However, little is known about the adaptive function of extrasynaptic NMDARs occurring mainly on dendritic shafts. Here, we find that in CA1 pyramidal neurons, back-propagating action potentials (bAPs) recruit shaft NMDARs exposed to ambient glutamate. In contrast, spine NMDARs are "protected," under baseline conditions, from such glutamate influences by peri-synaptic transporters: we detect bAP-evoked Ca(2+) entry through these receptors upon local synaptic or photolytic glutamate release. During theta-burst firing, NMDAR-dependent Ca(2+) entry either downregulates or upregulates an h-channel conductance (G(h)) of the cell depending on whether synaptic glutamate release is intact or blocked. Thus, the balance between activation of synaptic and extrasynaptic NMDARs can determine the sign of G(h) plasticity. G(h) plasticity in turn regulates dendritic input probed by local glutamate uncaging. These results uncover a metaplasticity mechanism potentially important for neural coding and memory formation.
突触 NMDA 受体（NMDAR）对于神经编码和可塑性至关重要。然而，对于主要发生在树突干上的细胞外 NMDAR 的适应功能知之甚少。在这里，我们发现 CA1 锥体神经元中的逆行动作电位（bAP）募集暴露于周围谷氨酸的轴突 NMDAR。相比之下，在基线条件下，突触旁转运蛋白使这些受体免受这种谷氨酸的影响：我们在局部突触或光解谷氨酸释放时检测到 bAP 引发的通过这些受体的 Ca(2+)内流。在θ爆发放电期间，NMDAR 依赖性 Ca(2+)内流根据突触谷氨酸释放是否完整或阻断，下调或上调细胞的 h 通道电导（G(h)）。因此，激活突触和细胞外 NMDAR 的平衡可以决定 G(h)可塑性的符号。反过来，G(h)可塑性调节通过局部谷氨酸非笼闭探测的树突输入。这些结果揭示了一种潜在的对神经编码和记忆形成很重要的代谢型可塑性机制。
