SYNAPTIC INTERACTIONS UNDERLYING MEMORY INDUCTION

作为记忆存储基质的生物物理事件有 在Hermissenda B细胞中有很好的记录，包括Ca 2+依赖性的 外向K+电流减少，导致膜电位增加 输入电阻和光引发的发生器电位。然而，尽管如此， 相对而言，我们对突触事件知之甚少， 这些生物物理学上的改变。事实上，许多提议的机制 被认为是生物物理记忆痕迹诱导的基础是 基于相关证据，在某些情况下未经检验。鉴于 各种细胞学习模型之间的差异是最 在归纳过程中，这些假设必须是 更仔细地检查。只有通过这样的检查， 普遍存在的原则，支配记忆的形成被辨别出来。在 目前的一系列实验，行为，生物物理和生物化学 记忆的索引将在关联的诱导期间被采用。 记忆痕迹Hermissenda将在所有实验中发挥作用， 它的神经系统相对简单， 允许鉴定和分离涉及 存储器存储 虽然细胞内Ca 2+和特定的神经递质已经被发现， 建议参与诱导联想记忆， Hermissenda，这些辅助因子相互作用以诱导新的 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和它们调节的事件， 与急性体内和体外条件反射相关的行为指数 体外记录和刺激动物的神经元 视觉前庭网络特定发射器的作用， 特别是GABA和5-HT，以及它们对神经元兴奋性的影响， 突触后神经元的生理状态的函数将是 考察实验诱导学习的机制 将被探索（例如，递质释放与突触后钙离子配对 ”（《礼记·礼记》） 在学习过程中和学习结束后。 的主要部分 目前的建议涉及传递激活的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，以及它们作为双调节器的功能， 突触后第二信使，可能有助于差异 突触后膜上K+传导的调节。的 确定和表征造成 有助于初始诱导和随后的简单存储 联想记忆，以及，可以解释突触的一般形式， 可塑性，可能有助于统一的发展， 记忆的细胞分析原理，因此可以提供 深入了解具体的干预措施和治疗方法， 记忆的获得和随后的恢复。

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.