Sweatt J D, Kandel E R
Howard Hughes Medical Institute, College of Physicians and Surgeons of Columbia University, New York 10032.
Nature. 1989 May 4;339(6219):51-4. doi: 10.1038/339051a0.
From certain perspectives, short- and long-term memory seem to be a single behavioural process whose duration is a graded function of the number of training trials. Yet some clinical conditions can dissociate short- from long-term memory in human beings, and inhibitors of protein or RNA synthesis can selectively block the long-term process in experimental animals. Studies of memory for sensitization in the gill- and siphon-withdrawal reflex in Aplysia indicate that both the behavioural similarities and the differences are reflected in intrinsic cellular mechanisms in the sensory and motor neurons participating in memory storage. Although the long-term change in the synaptic connection between the sensory and motor neurons resembles a graded extension of the short-term change, its induction is selectively blocked by inhibitors of transcription or translation. We have now examined the molecular mechanisms in the sensory neurons that might account for the graded similarity between short- and long-term memory, as well as those that might contribute to the differential sensitivity to inhibitors of macromolecular synthesis. We find that a single exposure to 5-HT (a transmitter released in response to behavioural sensitizing stimuli) or cyclic AMP (a second messenger for 5-HT), which produce short-term facilitation between the sensory and motor neurons lasting minutes, leads to a short-term phosphorylation of 17 substrate proteins that is not dependent on transcription or translation. Repeated or prolonged exposure to serotonin or cAMP, which induce long-term changes in synaptic transmission lasting one or more days, induce long-term changes in phosphorylation of the same 17 proteins that are now dependent for their induction on both translation and transcription. Thus, one of the functions of the genes and proteins required for long-term facilitation may be to maintain actively in the sensory neurons an increased phosphorylation of the same set of substrate proteins involved in eliciting the physiological effects of the short-term process.
从某些角度来看，短期记忆和长期记忆似乎是一个单一的行为过程，其持续时间是训练次数的分级函数。然而，一些临床病症能够使人的短期记忆与长期记忆分离，并且蛋白质或RNA合成抑制剂能够在实验动物中选择性地阻断长期过程。对海兔鳃和虹吸管收缩反射中的敏感化记忆的研究表明，行为上的相似性和差异都反映在参与记忆存储的感觉神经元和运动神经元的内在细胞机制中。虽然感觉神经元和运动神经元之间突触连接的长期变化类似于短期变化的分级扩展，但其诱导被转录或翻译抑制剂选择性地阻断。我们现在已经研究了感觉神经元中的分子机制，这些机制可能解释短期记忆和长期记忆之间的分级相似性，以及那些可能导致对大分子合成抑制剂的不同敏感性的机制。我们发现，单次暴露于5-羟色胺（一种响应行为敏感化刺激而释放的神经递质）或环磷酸腺苷（5-羟色胺的第二信使），它们在感觉神经元和运动神经元之间产生持续数分钟的短期易化，会导致17种底物蛋白的短期磷酸化，这一过程不依赖于转录或翻译。重复或长时间暴露于血清素或环磷酸腺苷，它们诱导持续一天或更长时间的突触传递长期变化，会诱导相同的17种蛋白质磷酸化的长期变化，现在它们的诱导依赖于翻译和转录。因此，长期易化所需的基因和蛋白质的功能之一可能是在感觉神经元中积极维持同一组底物蛋白的磷酸化增加，这些底物蛋白参与引发短期过程的生理效应。
