Department of Neurology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
PLoS One. 2012;7(5):e37542. doi: 10.1371/journal.pone.0037542. Epub 2012 May 22.
Two contrasting theories have been proposed to explain the mechanistic basis of short term memory. One theory posits that short term memory is represented by persistent neural activity supported by reverberating feedback networks. An alternate, more recent theory posits that short term memory can be supported by feedforward networks. While feedback driven memory can be implemented by well described mechanisms of synaptic plasticity, little is known of possible molecular and cellular mechanisms that can implement feedforward driven memory. Here we report such a mechanism in which the memory trace exists in the form of glutamate-bound but Mg(2+)-blocked NMDA receptors on the thin terminal dendrites of CA1 pyramidal neurons. Because glutamate dissociates from subsets of NMDA receptors very slowly, excitatory synaptic transmission can leave a silent residual trace that outlasts the electrical activity by hundreds of milliseconds. Read-out of the memory trace is possible if a critical level of these bound-but-blocked receptors accumulates on a dendritic branch that will allow these quasi-stable receptors to sustain a regenerative depolarization when triggered by an independent gating signal. This process is referred to here as dendritic hold and read (DHR). Because the read-out of the input is not dependent on repetition of the input and information flows in a single-pass manner, DHR can potentially support a feedforward memory architecture.
两种相互矛盾的理论被提出来解释短期记忆的机械基础。一种理论假设,短期记忆是由由反馈网络支持的持久神经活动来表示的。另一种、更新的理论假设,短期记忆可以由前馈网络来支持。虽然反馈驱动的记忆可以通过突触可塑性的描述良好的机制来实现,但对于可以实现前馈驱动记忆的可能的分子和细胞机制知之甚少。在这里,我们报告了这样一种机制,其中记忆痕迹以 CA1 锥体神经元的薄末梢树突上的谷氨酸结合但 Mg2+ 阻断的 NMDA 受体的形式存在。由于谷氨酸从 NMDA 受体的亚群中解离非常缓慢,兴奋性突触传递可以留下一个沉默的残留痕迹,其持续时间比电活动长数百毫秒。如果在一个树突分支上积累了一个临界水平的这些结合但被阻断的受体,这些准稳定的受体就可以在独立的门控信号触发时维持再生去极化,那么记忆痕迹的读取就成为可能。这个过程在这里被称为树突保持和读取(DHR)。由于输入的输出不依赖于输入的重复,信息以单通方式流动,DHR 可以潜在地支持前馈记忆架构。