FUNCTION OF GENES AND PROTEINS IN LEARNING AND MEMORY

基因和蛋白质在学习和记忆中的功能

• 批准号: 6393454
• 负责人: ARNOLD none ESKIN
• 金额: $ 25.34万
• 依托单位: UNIVERSITY OF HOUSTON
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-01-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6393454
• 关键词: Aplysia; Golgi apparatus; aminoacid biosynthesis; aminoacid metabolism; behavioral /social science research tag; behavioral habituation /sensitization; cyclic AMP; endoplasmic reticulum; genetic transcription; genetic translation; glutamates; glutamine; hippocampus; laboratory rat; learning; long term memory; membrane transport proteins; mitogen activated protein kinase; molecular psychobiology; neural information processing; neurons; neurotransmitter biosynthesis; protein biosynthesis; protein structure function; synapses; Aplysia; Golgi apparatus; aminoacid biosynthesis; aminoacid metabolism; behavioral /social science research tag; behavioral habituation /sensitization; cyclic AMP; endoplasmic reticulum; genetic transcription; genetic translation; glutamates; glutamine; hippocampus; laboratory rat; learning; long term memory; membrane transport proteins; mitogen activated protein kinase; molecular psychobiology; neural information processing; neurons; neurotransmitter biosynthesis; protein biosynthesis; protein structure function; synapses

The long-term goal of this research is to understand how changes in properties of neurons lead to the formation of memory and subsequent changes in behavior. The behavioral framework of our research is long-term sensitization of the defensive tail, siphon withdrawal reflex of Aplysia. Glutamatergic sensory neurons are key components of the reflex. Long-term presynaptic facilitation (LTF) at the sensory-motor synapse is mainly responsible for sensitization. We hypothesize that a number of properties of a sensory neuron must change in a coordinated fashion to produce LTF and store memory. Thus, we predict that the increase in transmitter release that occurs during LTF should be coordinated with an increase in uptake and synthesis of glutamate. In testing this hypothesis, we found that sensitization training leads to a substantial long-term increase in the Vmax of the high affinity neuronal glutamate transporter. In addition, we found that glutamine uptake was increased suggesting that glutamate synthesis was also increased. These findings provide the basis for molecular and biochemical studies on newly-discovered plastic properties of the sensory neuron. In particular, we will study molecular correlates of memory storage and expression in Aplysia and will extend these findings to research on long-term potentiation in the hippocampus of rats. The proposed research has 4 Specific Aims: Aim 1 is to determine the relationship between increases in glutamate uptake, glutamate synthesis, and behavioral sensitization. Aim 2 is to determine the cellular mechanisms that mediate coordinate regulation of glutamate uptake, synthesis, and long-term facilitation. Aim 3 is to determine whether the mechanisms responsible for the long-term increase in glutamate uptake involve synthesis of transporters and then transport through the ER-Golgi-vesicle transport pathway. Aim 4 is to determine the generality of regulation of uptake by studying glutamate uptake during long-term potentiation in the CA1 region of the hippocampus. Deficiencies in glutamate uptake have been implicated in a number of diseases (e.g., ALS, Hodgkin's, Alzheimer's). Glutamate appears to be a remarkably potent and rapidly-acting neurotoxin. This underlines the important role of glutamate uptake in the normal functioning of brains. Our research will help elucidate possible causes for decreased glutamate uptake in these diseases by identifying mechanisms responsible for long-term regulation of glutamate transporters.

这项研究的长期目标是了解神经元性质的变化如何导致记忆形成和随后的行为变化。 我们研究的行为框架是防御性尾巴的长期敏感，虹吸戒断反射的垂直质量。 谷氨酸能感觉神经元是反射的关键组成部分。 感觉运动突触的长期突触前促进（LTF）主要负责致敏。 我们假设感觉神经元的许多属性必须以协调的方式改变以产生LTF和存储记忆。 因此，我们预测，在LTF期间发生的发射机释放的增加应随着谷氨酸的摄取和合成的增加而进行协调。 在检验该假设时，我们发现敏化训练会导致高亲和力神经谷氨酸转运蛋白的VMAX长期大幅增加。 此外，我们发现增加了谷氨酰胺的摄取，这表明谷氨酸合成也增加了。 这些发现为感觉神经元新发现的塑性特性提供了分子和生化研究的基础。 特别是，我们将研究垂直溶质存储器存储和表达的分子相关性，并将这些发现扩展到研究大鼠海马长期增强的研究。 拟议的研究具有4个具体目标：目标1是确定谷氨酸摄取，谷氨酸合成和行为敏化的增加之间的关系。 目标2是确定介导谷氨酸摄取，合成和长期促进的介导的细胞机制。 AIM 3是确定负责长期增加谷氨酸摄取的机制是否涉及转运蛋白的合成，然后通过ER-Golgi-Vesicle运输途径进行转运。 目的4是通过研究海马CA1区域长期增强期间的谷氨酸摄取来确定摄取的普遍性。 谷氨酸摄取的缺陷与多种疾病有关（例如ALS，Hodgkin's，Alzheimer's）。 谷氨酸似乎是一种非常有效且迅速作用的神经毒素。 这强调了谷氨酸摄取在大脑正常功能中的重要作用。 我们的研究将有助于通过识别负责长期调节谷氨酸转运蛋白的机制来帮助阐明这些疾病中谷氨酸摄取减少的可能原因。