Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, United States of America.
PLoS One. 2014 Mar 18;9(3):e91954. doi: 10.1371/journal.pone.0091954. eCollection 2014.
Dynamin 1-3 isoforms are known to be involved in endocytotic processes occurring during synaptic transmission. No data has directly linked dynamins yet with normal animal behavior. Here we show that dynamin pharmacologic inhibition markedly impairs hippocampal-dependent associative memory. Memory loss was associated with changes in synaptic function occurring during repetitive stimulation that is thought to be linked with memory induction. Synaptic fatigue was accentuated by dynamin inhibition. Moreover, dynamin inhibition markedly reduced long-term potentiation, post-tetanic potentiation, and neurotransmitter released during repetitive stimulation. Most importantly, the effect of dynamin inhibition onto memory and synaptic plasticity was due to a specific involvement of the dynamin 1 isoform, as demonstrated through a genetic approach with siRNA against this isoform to temporally block it. Taken together, these findings identify dynamin 1 as a key protein for modulation of memory and release evoked by repetitive activity.
动力蛋白 1-3 异构体已知参与突触传递过程中的内吞作用。目前尚无数据直接将动力蛋白与正常动物行为联系起来。在这里，我们发现动力蛋白药理学抑制显著损害了海马体依赖性联想记忆。记忆丧失与重复刺激过程中发生的突触功能变化有关，这被认为与记忆诱导有关。动力蛋白抑制加重了突触疲劳。此外，动力蛋白抑制显著减少了重复刺激过程中长时程增强、强直后增强和神经递质的释放。最重要的是，动力蛋白抑制对记忆和突触可塑性的影响是由于动力蛋白 1 异构体的特定参与，这通过针对该异构体的 siRNA 进行基因敲除来证明。总之，这些发现确定了动力蛋白 1 是调节由重复活动引起的记忆和释放的关键蛋白。
