NEURONAL PATHWAYS UNDERLYING IN VITRO MOTOR LEARNING

体外运动学习的神经通路

• 批准号: 6639079
• 负责人: JOYCE KEIFER
• 金额: $ 14.37万
• 依托单位: UNIVERSITY OF SOUTH DAKOTA
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6639079
• 关键词: Chelonia; NMDA receptors; acoustic nerve; animal tissue; association learning; conditioning; electromyography; electrophysiology; electrostimulus; eye movements; fluoresceins; glutamate receptor; immunocytochemistry; in situ hybridization; inhibitor /antagonist; motor neurons; neural transmission; neuroanatomy; neuronal transport; paired stimuli; psychomotor function; reflex; synapses; trigeminal nerve

Insights into the processes of learning and memory have fundamental implications for understanding memory disorders such as occur during amnesia and Alzheimer's disease. Conditioned response learning is a simple form of associative learning. A promising model to study the neural mechanisms underlying associative learning is the classically conditioned eye-blink reflex. The classically conditioned eye-blink reflex has been widely adopted for physiologic studies of the mechanisms of associative learning. Simple in vitro model systems of associative learning have been established in several species of marine mollusks. These preparations have greatly facilitated our understanding of the neural mechanisms of learning and memory. Similar model systems of learning in vertebrates have previously been hampered by the technical limitations of maintaining the viability of large portions of intact neural tissue in isolation. This problem was recently overcome by the development of an in vitro brainstem-cerebellum preparation from the turtle which takes advantage of this species' extraordinary resistance to anoxia. Using this preparation, conditioning of reflex pathways was undertaken simply by using electrical stimulation of sensory nerves rather than more natural stimuli such as a tone or airpuff. Preliminary data show that a neural correlate of the conditioned eye-blink reflex, the abducens nerve response, can be generated entirely in vitro. Using this model, studies of the neural mechanisms underlying this form of motor learning will complement those studies using whole animal preparations. The goals of the present project are to elucidate the synaptic organization of the abducens eye-blink reflex circuitry and the mechanisms that may underlie associative learning in this in vitro preparation. The Specific Aims are: to evaluate whether NMDA receptors are required for classical conditioning by training the preparation in the presence or absence of the NMDA receptor antagonist APV, to examine the morphological distribution of synaptic inputs from nerves V (US) and pVIII (CS) onto abducens motoneurons using anterograde transport of Fluoro-Ruby and intracellular Lucifer yellow fills in fixed slices, to examine the morphological distribution of NMDA and non-NMDA glutamate receptors on LY-filled abducens motoneurons using immunocytochemistry, to identify the premotor pathways afferent to the abducens motoneurons using retrograde and anterograde tract tracing methods, and to determine the behavioral correlate of the abducens nerve CR by recording EMGs in a reduced preparation and by classical conditioning of the eye-blink reflex in alert turtles.

对学习和记忆过程的见解具有基本 对理解记忆障碍（例如发生）的影响 健忘症和阿尔茨海默氏病。 条件响应学习是 协会学习的简单形式。 一个有前途的模型 神经机制在经典上是经典的 有条件的眼光反射。 经典条件的眼光 反射已被广泛用于该机制的生理研究 协会学习。 简单的联想体外模型系统 在几种海洋软体动物中建立了学习。 这些准备工作极大地促进了我们对 学习和记忆的神经机制。类似的模型系统 脊椎动物中的学习以前受到技术的阻碍 保持大部分完整的生存能力的局限性 神经组织分离。最近克服了这个问题 开发体外脑干 - 脑系统制剂 利用该物种的非凡抗性的乌龟 缺氧。 使用此准备，反射途径的调理是 仅通过使用感觉神经的电刺激来进行 而不是更自然的刺激，例如音调或空调。 初步的 数据表明，条件眼光反射的神经相关， 可以完全在体外产生外表的神经反应。 使用 该模型，研究这种形式的神经机制 运动学习将补充所有动物的研究 准备。 本项目的目标是阐明 外围眼睛反射电路的突触组织和 可能是社会学习的基础的机制 准备。 具体目的是：评估NMDA受体是否 通过训练准备工作需要 NMDA受体拮抗剂APV的存在或不存在，以检查 神经V（US）和 PVIII（CS）使用ARTERORARDE的外星人运动神经元进行 荧光 - 荷利和细胞内路西法黄色填充固定片，到 检查NMDA和非NMDA谷氨酸的形态分布 使用免疫细胞化学的受体被填充的运动神经元， 识别伴随外皮运动神经元的前途径 使用逆行和顺行跟踪方法，并确定 通过记录EMG在 减少的准备和通过经典的眼光调节 警报海龟中的反射。