Department of Anatomy and Neurobiology, University of California, Irvine, California 92697, USA.
J Neurosci. 2012 Sep 12;32(37):12854-61. doi: 10.1523/JNEUROSCI.2024-12.2012.
Memory consolidation theory posits that newly acquired information passes through a series of stabilization steps before being firmly encoded. We report here that in rat and mouse, hippocampus cell adhesion receptors belonging to the β1-integrin family exhibit dynamic properties in adult synapses and that these contribute importantly to a previously unidentified stage of consolidation. Quantitative dual immunofluorescence microscopy showed that induction of long-term potentiation (LTP) by theta burst stimulation (TBS) activates β1 integrins, and integrin-signaling kinases, at spine synapses in adult hippocampal slices. Neutralizing antisera selective for β1 integrins blocked these effects. TBS-induced integrin activation was brief (<7 min) and followed by an ∼45 min period during which the adhesion receptors did not respond to a second application of TBS. Brefeldin A, which blocks integrin trafficking to the plasma membrane, prevented the delayed recovery of integrin responses to TBS. β1 integrin-neutralizing antisera erased LTP when applied during, but not after, the return of integrin responsivity. Similarly, infusions of anti-β1 into rostral mouse hippocampus blocked formation of long-term, object location memory when started 20 min after learning but not 40 min later. The finding that β1 integrin neutralization was effective in the same time window for slice and behavioral experiments strongly suggests that integrin recovery triggers a temporally discrete, previously undetected second stage of consolidation for both LTP and memory.
记忆巩固理论认为，新获得的信息在被牢固编码之前，要经过一系列的稳定步骤。我们在这里报告，在大鼠和小鼠中，海马细胞黏附受体属于β1 整联蛋白家族，在成年突触中表现出动态特性，这些特性对先前未被识别的巩固阶段有重要贡献。定量双免疫荧光显微镜显示，通过θ爆发刺激（TBS）诱导长时程增强（LTP）会激活成年海马切片中突触的β1 整联蛋白和整联蛋白信号激酶。针对β1 整联蛋白的中和抗血清阻断了这些效应。TBS 诱导的整联蛋白激活是短暂的（<7 分钟），随后是大约 45 分钟的时间，在此期间，粘附受体对 TBS 的第二次应用没有反应。布雷非德菌素 A 可阻止整联蛋白向质膜转运，从而阻止了整联蛋白对 TBS 的反应的延迟恢复。β1 整联蛋白中和抗血清在整合素反应恢复时应用时可消除 LTP，但在整合素反应恢复后应用则不能。同样，当在学习后 20 分钟而不是 40 分钟后开始将抗-β1 注入到小鼠海马的前颅时，它会阻断长期的物体位置记忆的形成。整联蛋白中和在切片和行为实验中的相同时间窗口内有效这一发现强烈表明，整合素的恢复触发了 LTP 和记忆的先前未检测到的第二个暂时离散的巩固阶段。
