Transgenic Dissection of the Neural Circuitry of the Intact Hippocampal Formation

完整海马结构神经回路的转基因解剖

• 批准号: 8706967
• 负责人: CLIFFORD G KENTROS
• 金额: $ 41.82万
• 依托单位: UNIVERSITY OF OREGON
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8706967
• 关键词: Address; Alzheimer' s Disease; Amplifiers; Animals; Area; Automobile Driving; Behavioral; Biological Models; Brain; Brain region; Cell Death; Cells; Cereals; Dementia; Dissection; Electronics; Engineering; Environment; Epilepsy; Functional disorder; Generations; Hand; Health; Hippocampal Formation; Hippocampus (Brain); Human; Lead; Learning; Lesion; Light; Link; Medial; Membrane Potentials; Memory; Memory Disorders; Memory impairment; Modeling; Molecular Genetics; Mus; N-Methyl-D-Aspartate Receptors; Neurons; Nodal; Output; Patients; Pattern; Personal Satisfaction; Pharmaceutical Preparations; Plastics; Play; Population; Process; Research; Rodent; Role; Specific qualifier value; Stimulus; Stroke; Techniques; Testing; Theoretical model; Time; Transgenes; Transgenic Mice; Transgenic Organisms; Trauma; age related; awake; cell transformation; cell type; electric impedance; entorhinal cortex; experience; millisecond; neural circuit; neuropathology; novel; optogenetics; public health relevance; receptive field; relating to nervous system; research study; response; spatiotemporal; tool; transgene expression

DESCRIPTION (provided by applicant): This application describes experiments that analyze the neural circuitry of the hippocampal formation (HF), the brain area most clearly implicated in memory and disorders such as Alzheimer's and related dementias. It combines neuron-specific transgene expression with electrophysiological techniques to study the transformation of information in the mammalian hippocampal formation at the cellular and network level. The approach is similar to the nodal analysis performed by engineers to analyze electronic circuits. Here, however, the nodes are neural cell types rather than electrical components. The nodes are specified by transgenic "driver" lines which direct the expression of various transgenes (depending upon which transgenic "payload" lines they are crossed to) enabling cell type specific changes in activity. Performing this nodal analysis, we manipulate the activity of one node while recording from others, much as when a potentiometer controlling the impedance of an amplifier circuit changes audio output when manipulated. We do so by driving the expression of transgenes which increase or decrease the membrane potential of neurons when activated either by specific drugs or wavelengths of light. We can then manipulate the activity of an identifiable population of primary neurons in the HF circuit while recording the activity of others gaining a functional understanding of how information is transformed from one region to the next.

描述（由申请人提供）：本申请描述了分析海马结构（HF）神经回路的实验，海马结构是与记忆和疾病（例如阿尔茨海默病和相关痴呆症）最明显相关的大脑区域。它将神经元特异性转基因表达与电生理技术相结合，在细胞和网络水平上研究哺乳动物海马结构中的信息转化。该方法类似于工程师为分析电子电路而进行的节点分析。然而，这里的节点是神经细胞类型而不是电子元件。这些节点由转基因“驱动”系指定，这些系指导各种转基因的表达（取决于它们与哪些转基因“有效负载”系杂交），从而实现细胞类型特异性的活性变化。执行此节点分析时，我们在记录其他节点的同时操纵一个节点的活动，就像控制放大器电路阻抗的电位器在操纵时改变音频输出一样。我们通过驱动转基因的表达来实现这一点，当被特定药物或波长的光激活时，转基因会增加或减少神经元的膜电位。然后，我们可以操纵高频回路中可识别的初级神经元群的活动，同时记录其他神经元的活动，从而获得对信息如何从一个区域转换到下一个区域的功能性理解。