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SYNAPTIC INTERACTIONS UNDERLYING MEMORY INDUCTION

记忆感应背后的突触相互作用

基本信息

批准号：
2675025
负责人：
LOUIS D MATZEL
金额：
$ 9.1万
依托单位：
RUTGERS, THE STATE UNIV OF N.J.
依托单位国家：
美国
项目类别：
财政年份：
1994
资助国家：
美国
起止时间：
1994-08-01 至 1999-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2675025
关键词：
Hermissenda arachidonate behavioral /social science research tag calcium flux conditioning gamma aminobutyrate guanine nucleotide binding protein learning membrane potentials memory molecular psychobiology serotonin visual photoreceptor

项目摘要

The biophysical events which serve as substrates for memory storage have been well documented in Hermissenda B cells, and include a Ca2+-dependent reduction of outward K+ currents and a resultant Increase in membrane input resistance and light-elicited generator potentials. Nevertheless, comparatively little is known about the synaptic events which culminate in these biophysical modifications. In fact, many of the proposed mechanisms thought to underlie the induction of the biophysical memory trace are based on correlative evidence and in some cases are untested. Given that the disparities between various cellular models of learning are most pronounced with regard to the induction process, these assumptions must be more closely examined. Only through such an examination will those ubiquitous principles which govern memory formation be discerned. In the present series of experiments, behavioral, biophysical, and biochemical indices of memory will be employed during induction of an associative memory trace. Hermissenda will serve in all experiments, and is well suited for such an analysis in that its relatively simple nervous system permits the identification and isolation of single cells involved in memory storage. Although both intracellular Ca2+ and specific neurotransmitters have been proposed to participate in the induction of associative memory in Hermissenda, the mechanism by which these cofactors interact to induce new memories is vague. The experiments described here are intended to address the role of these cofactors and the events that they regulate, via behavioral indices of conditioning in conjunction with acute in vivo and in vitro recording and stimulation of identified neurons in the animal's visual-vestibular network. The role of specific transmitters, in particular, GABA and 5-HT, and their effects on neuronal excitability as a function of the physiological state of the postsynaptic neuron will be examined. Mechanisms that underlie trial-by-trial induction of learning will be explored (e.g.,transmitter release paired with postsynaptic Ca2+ elevation), and will be distinguished from the consolidation that takes place both during and after the learning event. A major portion of the present proposal concerns the role of transmitter-activated GTP-binding proteins, both as mediators of Visual-vestibular interactions in Hermissenda, as well as in their function as dual regulators of postsynaptic second messengers which may contribute to the differential modulation of K+ conductance on the postsynaptic membrane. The identification and characterization of mechanisms which causally contribute to Initial induction and subsequent storage of a simple associative memory, and, which can account for a general form of synaptic plasticity, are likely to contribute to the development of unifying principles in the cellular analysis of memory, and may thus provide insight Into specific interventions and treatments to benefit the acquisition and subsequent retrieval of memories.

作为记忆存储基质的生物物理事件已经 Hermissenda B 细胞中已得到充分记录，并且包括 Ca2+ 依赖性外向 K+ 电流的减少以及由此产生的膜的增加输入电阻和光引发的发电机电位。尽管如此，对于最终导致的突触事件知之甚少这些生物物理改变。事实上，许多提议的机制人们认为生物物理记忆痕迹诱导的基础是基于相关证据，并且在某些情况下未经测试。鉴于各种细胞学习模型之间的差异是最大的就归纳过程而言，这些假设必须是更仔细地检查。只有通过这样的检查，那些认识到控制记忆形成的普遍原则。在呈现一系列行为、生物物理和生物化学实验在联想的诱导过程中将使用记忆索引记忆痕迹。 Hermissenda 将参与所有实验，并且状况良好适合这样的分析，因为它的神经系统相对简单允许识别和分离参与的单细胞记忆存储。尽管细胞内 Ca2+ 和特定神经递质已被建议参与联想记忆的诱导 Hermissenda，这些辅助因子相互作用以诱导新的机制记忆是模糊的。这里描述的实验旨在解决这些辅助因子的作用及其调节的事件，通过与急性体内调节相关的行为指标体外记录和刺激动物体内已识别的神经元视觉前庭网络。特定发射机的作用特别是 GABA 和 5-HT，以及它们对神经元兴奋性的影响突触后神经元生理状态的函数是检查了。逐项试验诱导学习的机制将被探索（例如，递质释放与突触后 Ca2+ 配对高程），并将与需要的合并区分开来放置在学习活动期间和之后。其中很大一部分目前的提案涉及递质激活的 GTP 结合的作用蛋白质，两者都是视觉前庭相互作用的介质 Hermissenda 以及其作为双重调节器的功能突触后第二信使可能有助于差异突触后膜 K+ 电导的调节。这因果机制的识别和表征有助于简单的初始归纳和随后的存储联想记忆，并且，它可以解释突触的一般形式可塑性，可能有助于统一的发展记忆细胞分析的原理，因此可以提供深入了解有利于患者的具体干预措施和治疗方法记忆的获取和随后的检索。