Plasticity of Voltage Gated Ion Channels in Mammalian Learning and Memory

哺乳动物学习和记忆中电压门控离子通道的可塑性

基本信息

批准号：
8729044
负责人：
JOHN T GREEN
金额：
$ 18.87万
依托单位：
UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-01 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8729044
关键词：
Address Adult Affect Agreement Alzheimer&apos s Disease American Applications Grants Basic Science Behavior Behavioral Biochemical Biological Assay Biological Models Blinking Brain Cell Nucleus Centers for Disease Control and Prevention (U.S.)Cerebellar cortex structure Cerebellum Child Data Dendrites Dimensions Disease Extinction (Psychology)Figs - dietary Gated Ion Channel Goals Health Human Infusion procedures Invertebrates Ion Channel Ions Journals Learning Learning Disabilities Ligands Link Literature Long-Term Depression Long-Term Potentiation Mammals Memory Memory Disorders Mental Depression Mental Health Mission Modeling Molecular Myoepithelial cell National Institute of Neurological Disorders and Stroke Nervous system structure Neurobiology Neuromodulator Neurons Neurosciences Output Paper Pathology Play Population Positioning Attribute Post-Traumatic Stress Disorders Presynaptic Terminals Publishing Purkinje Cells Rattus Regulation Research Research Project Grants Role Secretin Sleep Disorders Slice Stimulus Surface Synapses Synaptic plasticity Testing United States National Institutes of Health aged base conditioning cost design effective therapy human old age (65+)in vivo inhibitor/antagonist insight interdisciplinary collaboration nervous system disorder neuromechanism novel public health relevance relating to nervous system response therapeutic target trafficking voltage voltage gated channel

项目摘要

DESCRIPTION (provided by applicant): Understanding the neural mechanisms of learning and memory is of tremendous importance to human health. Alzheimer's Disease alone is estimated to affect 2.6-5.1 million Americans aged 65 years and older and to have annual costs exceeding $100 billion (NIH Fact Sheet: Alzheimer's Disease). Despite steady progress in understanding the neural basis of learning and memory, there are still major gaps in our understanding. These gaps make designing specific and effective treatments for memory disorders extremely challenging, if not impossible. This grant application addresses a major research gap in the neurobiology of mammalian learning and memory literature. Specifically, the bulk of the research on the neuronal substrates of mammalian learning and memory has focused on synaptic plasticity and regulation of ligand-gated ion channels. The proposed research will fill a major research gap by examining how regulation of voltage-gated ion channels contributes to mammalian learning and memory. In this research, we will utilize a form of mammalian learning and memory whose neural substrates in the cerebellum are well-understood (eyeblink conditioning) and study a voltage-gated ion channel whose regulation is well-understood and whose distribution in the cerebellum is highly localized (Kv1.2). Combining eyeblink conditioning and Kv1.2 gives us a "model system" for answering general questions about how regulation of voltage-gated ion channels contributes to mammalian learning and memory. We combine behavior, intracranial infusions, and in vivo recording to explore how and when Kv1.2 function in different regions of cerebellar cortex contributes to acquisition, expression, and extinction of eyeblink conditioning in rats and we combine behavior and biochemical assays to explore how eyeblink conditioning in rats affects cerebellar cortical Kv1.2 regulation and function.

描述（由申请人提供）：了解学习和记忆的神经机制对人类健康至关重要。据估计，仅阿尔茨海默氏病就会影响65岁及65岁以上的26-510万美国人，年成本超过1000亿美元（NIH情况说明书：阿尔茨海默氏病）。尽管在理解学习和记忆的神经基础方面稳步进步，但我们的理解仍然存在主要差距。这些差距使设计对记忆障碍的特定有效治疗非常具有挑战性，即使不是不可能。该赠款应用程序解决了哺乳动物学习和记忆文献神经生物学的主要研究差距。具体而言，关于哺乳动物学习和记忆的神经元底物的大部分研究都集中在配体门控离子通道的突触可塑性和调节上。拟议的研究将通过研究电压门控离子通道的调节如何有助于哺乳动物的学习和记忆来填补重大的研究差距。在这项研究中，我们将利用一种哺乳动物学习和记忆的形式，其在小脑中的神经底物很好地理解了（Eykeblink条件），并研究了电压门控的离子通道，其调节且在小脑中的分布是高度局部的（KV1.2）。结合眉毛条件和KV1.2为我们提供了一个“模型系统”，用于回答有关电压门控离子通道如何有助于哺乳动物学习和记忆的一般问题。 We combine behavior, intracranial infusions, and in vivo recording to explore how and when Kv1.2 function in different regions of cerebellar cortex contributes to acquisition, expression, and extinction of eyeblink conditioning in rats and we combine behavior and biochemical assays to explore how eyeblink conditioning in rats affects cerebellar cortical Kv1.2 regulation and function.