Genetic, Physiological, and Behavioral Studies of Memory

CCNR的长期目标是阐明哺乳动物学习和记忆的分子、细胞、神经元系综和神经元回路机制。CCNR在三个复杂的层次上解决这个问题：首先，了解突触可塑性及其调节的基本机制。第二，了解突触可塑性如何在海马和新皮质中维持单个或整体神经元活动。第三，了解单个和整体神经元活动如何代表学习和记忆的特定方面。 此外，该中心旨在整合在这些复杂性的多个层次上所做的研究结果，以达到对记忆的全面和连贯的理解。为了实现这些目标，来自麻省理工学院的六名研究人员和来自索尔克研究所的一名研究人员，他们有着共同的知识兴趣，但来自不同的领域，具有互补的专业知识，从分子，细胞和遗传神经生物学到电生理学，计算和行为 神经科学，将联手追求30个具体目标，其中许多将在协同合作中进行。对于可塑性的基本机制，该中心建议将体外电生理记录和荧光介导的成像技术应用于用药理学试剂处理或来自基因工程啮齿动物的细胞培养和脑切片制剂。为了了解突触可塑性如何帮助单个神经元或整体神经元活动，该中心建议使用多电极记录技术 在自由活动的啮齿类动物中。为了了解神经元活动如何代表编码，巩固或检索的记忆信息，该中心建议研究猴子和啮齿动物的神经元群体进行特定的目标导向的任务。该中心的许多项目使用啮齿动物，但猴子也用于复杂现象的研究，例如识别记忆回忆的“执行控制”的神经元相关性。 最后，为了将发生在多个复杂水平的神经事件或过程与行为表现记忆相关联，该中心提出产生其中神经功能的特定遗传破坏在空间和/或时间上具有选择性的小鼠品系，并使它们经受上述所有分析方法。七个个别项目将由三个核心提供支持，这些核心提供关键小鼠突变品系的生产和维护以及行政服务。该中心的基础研究与心理健康和疾病有关，因为记忆衰退和损伤是衰老和神经退行性疾病的标志。

The long-term objective of the proposed CCNR is to elucidate the molecular, cellular, neuronal ensemble, and neuron circuitry mechanisms of mammalian learning and memory. The CCNR attacks the problem at three levels of complexity: First, to understand the elementary mechanisms of synaptic plasticity and its regulation. Second, to understand how synaptic plasticity subserves single or ensemble neuron activities in the hippocampus and neocortex. Third, to understand how single and ensemble neuron activities represent specific aspects of learning and memory. Further, the Center seeks to integrate findings made at these multiple levels of complexity to reach a comprehensive and coherent understanding of memory. To accomplish these objectives, six investigators from MIT and one from the Salk Institute, who share common intellectual interests and yet come from different fields with complementary expertise ranging from molecular, cellular, and genetic neurobiology to electrophysiology and computational and behavioral neurosciences, will join forces to pursue 30 Specific Aims, many of which are to be carried out in synergistic collaborations. For the elementary mechanisms of plasticity, the Center proposes to apply in vitro electrophysiological recording and fluorescence-mediated imaging techniques to cell-culture and brain slice preparations treated with pharmacological agents or derived from genetically engineered rodents. To understand how synaptic plasticity subserves single neuron or ensemble neuron activities, the Center proposes to use multi-electrode recording techniques in freely behaving rodents. In order to understand how neuronal activities represent encoded, consolidated or retrieved memory information, the Center proposes to study populations of neurons in monkeys and rodents undergoing a specific goal-oriented task. Many projects at the Center use rodents, but monkeys are also used for the study of complex phenomena such as the identification of the neuronal correlates of "executive control" of memory recall. Finally, in order to correlate neural events or processes occurring at multiple levels of complexity with behaviorally manifested memory, the Center proposes to generate mouse strains in which a specific genetic disruption of neural function is spatially and/or temporally selective, and subject them to all the analytical methods described above. Seven Individual Projects are to be supported by three Cores which provide production and maintenance of key mouse mutant strains and administrative services. The Center's basic research is relevant to mental health and illness because mnemonic decline and impairments are a hallmark of aging and neurodegenerative disease.