What molecular steps determine the time course of the memory for short-term sensitization in Aplysia?

What molecular steps determine the time course of the memory for short-term sensitization in Aplysia?
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哪些分子步骤决定了海兔短期敏化记忆的时间过程?

DOI:
10.1101/sqb.1983.048.01.084
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发表时间:
1983
期刊:
Cold Spring Harbor symposia on quantitative biology
影响因子:
--
通讯作者:
Kandel,ER
Kandel,ER
中科院分区:
--
文献类型:
--
作者:
Schwartz,JH;Bernier,L;Castellucci,VF;Palazzolo,M;Saitoh,T;Stapleton,A;Kandel,ER

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学习和记忆是一个古老的问题,现在开始在分子水平上进行分析。根据心理学家的定义,学习是由经验产生的行为改变,记忆是保持学习的机制。最近对无脊椎动物的研究提出了一个工作假设,即至少某些形式的学习可以通过特定突触强度的变化产生,这些突触持续数分钟到数小时(短期记忆)或数周或更长时间(长期记忆)(Jacobs和Gelperin 1981; Kandel和Schwartz 1982)。这些动物的行为之所以改变,是因为在这些突触末端,神经递质的释放被增强或减弱。释放的递质的量由Ca ~(2+)离子通过通道流入末梢来控制,现在认为这些通道由集中在神经末梢膜中的特定蛋白质组成(Koester和Byrne 1980; Reichardt和Kelly 1983)。根据这一工作假说,对这些离子通道在短期和长期学习形式中的调节过程的鉴定和表征将构成对记忆的分子解释。海洋软体动物,Aaplasia,在实验上有利于研究学习基础的生化步骤,因为可以鉴定出介导被经验改变的行为的神经元,细胞足够大,可以注射各种分子作为探针。因此,可以直接研究这些探针对学习过程的作用。例如,已经注射了小分子如cAMP、大分子如蛋白激酶和蛋白抑制剂,以测试它们对细胞功能的影响(Castellucci等,1980,1982; Kaczmarek等,1980)。失智症神经元也可以提供足够的材料,用于对实际发生生理事件的细胞进行生化分析。
Learning and memory are age-old problems that are beginning to yield to analysis at the molecular level. As defined by psychologists, learning is an alteration of behavior produced by experience, and memory is the mechanism by which the learning is retained. Recent studies with invertebrates have given rise to the working hypothesis that at least some forms of learning can be produced by changes in the strength of specific synapses that persist for periods of minutes to hours (shortterm memory) or for weeks or longer (long-term memory)(Jacobs and Gelperin 1981; Kandel and Schwartz 1982). The behavior of these animals is altered because, at these synaptic terminals, release of neurotransmitter is enhanced or diminished. The amount of transmitter released is controlled by the flow of Ca §§ ions into the terminal through channels that now are thought to consist of specific proteins that are concentrated in the membrane of nerve endings (Koester and Byrne 1980; Reichardt and Kelly 1983). Identification and characterization of the processes by which these ion channels are regulated both in the short-term and in the long-term forms of learning would, according to this working hypothesis, constitute a molecular explanation of memory.The marine mollusc, Aplysia, is experimentally advantageous for studying the biochemical steps that underlie learning because the neurons mediating the behavior that is altered by experience can be identified, and the cells are large enough to be injected with a variety of molecules as probes. The action of these probes on the learning process can therefore be studied directly. For example, small molecules like cAMP, macromolecules like protein kinase, and protein inhibitors have been injected to test their effects on cellular function (Castellucci et al. 1980, 1982; Kaczmarek et al. 1980). Aplysia neurons can also provide sufficient material for biochemical analysis on the very cells in which the physiological events are actually taking place.