SYNAPTIC INTERACTIONS UNDERLYING MEMORY INDUCTION

作为记忆存储底物的生物物理事件具有 在HermissendaB细胞中被很好地记录下来，并包括一种钙依赖的 外向K+电流的减少和由此导致的膜上的增加 输入电阻和光激发电机电势。不过， 对于最终导致突触活动的突触事件，我们知之甚少 这些生物物理修饰。事实上，许多拟议的机制 生物物理记忆痕迹诱导的基础思想是 基于相关证据，在某些情况下未经检验。考虑到 不同的学习细胞模型之间的差异最大 关于归纳过程，这些假设必须是 更仔细地审查。只有通过这样的审查，那些 支配记忆形成的无处不在的原则是显而易见的。在 目前的一系列实验，行为，生物物理和生化 在联想的诱导过程中将使用记忆索引 记忆痕迹。厄米森达将在所有的实验中服务，并且很好。 适合于这样的分析，因为它相对简单的神经系统 允许识别和分离涉及到的单个细胞 内存存储。 尽管细胞内钙离子和特定的神经递质 建议参与联想记忆的诱导 厄米森达，这些辅助因素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 这些辅因子的作用及其调节的事件，通过 急性在体和急性条件反射的行为学指标 体外记录和刺激动物大脑中已识别的神经元 视觉前庭网络。特定传递器的作用，在 尤其是GABA和5-羟色胺，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 检查过了。一次又一次学习诱导的基础机制 将探索(例如，递质释放与突触后钙离子配对 高程)，并将与需要 在学习活动期间和之后都放置。世界上的大部分 目前的建议涉及递质激活的GTP结合的作用 蛋白质都是视觉-前庭相互作用的媒介 埃尔米森达，以及他们作为双重监管者的职能 可能与这种差异有关的突触后第二信使 K+电导对突触后膜的调制作用这个 致病机制的鉴定和表征 有助于初始诱导和随后存储简单的 联想记忆，和，这可以解释突触的一般形式 可塑性，很可能有助于统一的发展 在记忆的细胞分析中的原理，因此可以提供 深入了解具体的干预措施和治疗方法，以造福于 记忆的获取和随后的检索。

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.