EFFECT OF CNS LESIONS ON DRUG ACTION

兔瞬膜的巴甫洛夫条件反射 反应，一种角膜-第VIth神经反射，被普遍同意 提供一种可靠的联想学习和记忆测量方法。 这个模型系统将被用来识别解剖路径 和神经化学系统参与学习和记忆以及 检查行为和神经化学过程，通过 药物可以改变学习和记忆。实验将是 在三个主要目标下实施，这将提供汇聚 来源的方法这些基本过程的额外知识。 目标1将检查那些被认为是 在收购和/或 条件反应的表现。这将包括一次彻底的 审查最近关于小脑是必不可少的主张 通过使用皮质(VIth叶)来学习运动动作 和皮质下(间位)损害的小脑和 输注利多卡因造成的可逆性损伤。这个 然后将使用可逆性损伤来确定是否 介词对于条件性语言的习得是必不可少的 回应。这些可逆的损伤也将被用来识别 条件性和非条件性反应的其他途径。目标 2将检测~3H-和~(14)C-2-脱氧-D-葡萄糖在 应用定量放射自显影技术的双同位素技术 识别大脑中不同激活的区域 条件句和无条件句的连续表示形式 刺激和这种异质突触易化的神经元 活动可以预测随后的学习速度。例如, 有些药物对学习的影响似乎次于 它们增加或减少这种异突触的能力 促进。AIM 3将使用脑室内注射药物 激活或抑制cAMP系统以检测其作用 这是学习和药物影响的第二个信使 学习。这样的知识应该提供关于 人类学习和记忆障碍涉及的神经系统 (例如，阿尔茨海默病)，并确定可能是 对他们的治疗很有效。

Pavlovian conditioning of the rabbit's nictitating membrane response, a corneal-VIth nerve reflex, is generally agreed to provide a reliable measure of associative learning and memory. This model system will be used to identify the anatomical pathways and neurochemical systems involved in learning and memory and to examine the behavioral and neurochemical processes through which drugs act to alter learning and memory. Experiments will be carried out under three major aims that will provide converging approaches to origin additional knowledge of these basic processes. Aim 1 will examine those brain regions that have been suggested to play an essential or important role in the acquisition and/or performance of conditioned responses. This will include a thorough examination of recent proposals that the cerebellum is essential for the learning of motor acts by the use of cortical (VIth lobe) and subcortical (interpositus) lesions of the cerebellum and from reversible lesions produced by infusion of lidocaine. The reversible lesion will then be employed to establish whether interpositus is essential for the acquisition of conditioned responses. These reversible lesions will also be used to identify other pathways of the conditioned and unconditioned response. Aim 2 will examine the uptake of 3H- and 14C-2-deoxy-D-glucose in a double isotope technique employing quantitative autoradiography to identify the areas of brain that are differentially activated by the contiguous presentation of a conditioned and unconditioned stimulus and whether such heterosynaptic facilitation of neuronal activity can predict subsequent rates of learning. For example, the effect of some drugs on learning appear to be secondary to their ability to increase or decrease such heterosynaptic facilitation. Aim 3 will use intraventricular injections of drugs that activate or inhibit the cAMP system to examine the role of this second messenger in learning and in the effects of drugs on learning. Such knowledge should provide clues concerning the neural systems involved in human disorders of learning and memory (e.g., Alzheimer's disease) and identify the drugs that might be effective in their treatment.