ROLE OF NMDA RECEPTORS IN CORTICAL PLASTICITY

NMDA 受体在皮质可塑性中的作用

• 批准号: 3414171
• 负责人: KEVIN FOX
• 金额: $ 13.94万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-08-01 至 1992-09-23
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3414171
• 关键词: NMDA receptors; animal age group; association cortex; cerebral cortex; laboratory rat; neural plasticity; neuroanatomy; sensory deprivation; synapses

The goal of the proposed experiments is to understand the mechanisms and rules which govern the modification of synaptic strength in the cerebral cortex throughout life. Three hypotheses about experience-dependent cortical plasticity will be tested; namely, 1) that the enduring effect of limited periods of abnormal somatic sensory experience on cortical synapses is greatest in early postnatal life, 2) that operative N-methyl-D-Aspartate (NMDA) receptors are necessary for experience-dependent synaptic modification in cortex at all ages and 3) that NMDA effects will be greatest in the input zone (layer IV) early in life, greatest in the associational zone (layers II + III) later in life and absent from all layers in extreme old age. Four sets of experiments are proposed to test these postulates: 1) Studies of the effect of sensory deprivation g aU but 1 whisker for 30 days), beginning at postnatal ages ranging from newborn to old age, on the "cortical domain" of the single "used" or "experienced" whisker, 2) Studies to determine whether this type of sensory deprivation effect depends on cortical and/or subcortical plasticity, 3) Studies of the effect of blocking NMDA receptors with D-APV on cortical cell responses to sensory stimulation before and after the end of the above defined critical period and 4) Studies of the effect of chronic administration of NMDA receptor blockers on experiencedependent expansion of the cortical domains. These experiments will describe the extent of use. dependent changes induced in whisker to barrel field system throughout the normal lifespan of a rat. They will show the degree to which cortical neurons in each layer are depend upon NMDA receptors to effect the synaptic modification required for these changes. If changes in the cortical domain of a single whisker do occur, but do not depend upon NMDA receptors, the results may emphasize the need to consider additional or even alterative mechanisms. The detailed nature of the experiments will provide information to guide future studies on the mechanisms underlying, activity-dependent cortical plasticity.

拟议实验的目的是了解机制和 控制大脑突触强度修改的规则 一生的皮质。关于经验依赖性的三个假设 皮质可塑性将进行测试；即，1） 皮质突触异常的躯体感觉体验有限的时期 在产后早期生活中最伟大，2）手术N-甲基-D-天冬氨酸 （NMDA）受体对于经验依赖性突触是必需的 在所有年龄段的皮质中修改和3）NMDA效应将是 在生命早期最大的输入区（第四层），最伟大的 在生命的后期，与所有人相关区（层II + III），没有所有人 极端年龄的层。提出了四组实验进行测试 这些假设：1）对感觉剥夺的影响G au的研究，但 1晶须30天），从新生儿到产后年龄开始 老年，在单个“二手”或“经验丰富”的“皮质领域”上 晶须，2）研究确定这种感觉剥夺是否 效果取决于皮质和/或皮层可塑性，3）研究 用D-APV阻断NMDA受体对皮质细胞反应的影响 上述定义临界之前和之后的感觉刺激 周期和4）研究NMDA长期给药的影响 受体阻滞剂在皮质结构域的经验丰富的扩展上。 这些实验将描述使用程度。相关变化 在整个正常寿命中，在晶须中诱导了枪管场系统 老鼠。他们将显示每一层的皮质神经元的程度 取决于NMDA受体来实现所需的突触修饰 这些更改。如果单个晶须的皮质域发生变化 发生，但不依赖NMDA受体，结果可能会强调 需要考虑其他甚至更改的机制。详细 实验的性质将提供信息来指导未来的研究 关于活动依赖性皮质可塑性的机制。