CRCNS: Input/Output Relationship in CA3 Pyramidal Cells

CRCNS：CA3 锥体细胞的输入/输出关系

• 批准号: 7474611
• 负责人: GIORGIO A ASCOLI
• 金额: $ 29.04万
• 依托单位: GEORGE MASON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7474611
• 关键词: Address; Afferent Pathways; Alzheimer' s Disease; Anatomy; Apical; Archives; Area; Arts; Back; Behavior; Biophysics; Calcium; Cells; Characteristics; Cholinergic Agents; Chromosome Pairing; Classification; Complex; Computer Simulation; Condition; Data; Dendrites; Depth; Detection; Distal; Failure; Figs - dietary; Fire - disasters; Foundations; Frequencies; GABA Antagonists; Glutamates; Goals; Hippocampus (Brain); Human; Image; Individual; Internet; Interneurons; Kinetics; Knowledge; Link; Location; Maps; Measures; Medial; Mediating; Membrane; Memory; Methods; Mission; Modeling; Morphology; Myoepithelial cell; Neurons; Normal Cell; Numbers; Output; Pathway interactions; Pattern; Peer Review; Perforant Pathway; Pharmacology; Physiology; Play; Positioning Attribute; Probability; Property; Public Health; Publications; Pyramidal Cells; Range; Recurrence; Relative (related person); Research; Rodent; Role; Source; Specificity; Statistical Distributions; Structure; Synapses; Techniques; Time; Training; Trees; Variant; age related; base; cholinergic; cognitive function; density; dentate gyrus; entorhinal cortex; granule cell; mossy fiber; patch clamp; reconstruction; research study; response; simulation; stellate cell; symposium; theories; voltage; voltage clamp; voltage gated channel; way finding

DESCRIPTION (provided by applicant): CA3 pyramidal cells (CA3pcs) constitute a central crossroad of synaptic integration in the hippocampus, and play a key role in spatial mapping and memory storage. CA3pcs are monosynaptically excited by the entorhinal cortex, dentate granule cells, and other CA3pcs. The electrophysiological repertoire of CA3pcs includes single spiking and bursting, spanning a broad range of frequencies. Despite a general understanding of the anatomy and physiology of CA3pcs, little is known about the correspondence between a given pattern of synaptic inputs and the resulting firing output. This information, which is essential to relate hippocampal activity and function, constitutes the main goal of this project. First, we will investigate CA3pc dendrite biophysics (passive properties, channel distributions and kinetics), and the unitary synaptic inputs from each pathway. This will be achieved with voltage- and current-clamp recordings, calcium imaging, and the creation of a detailed, data-driven computational model. Next, the firing patterns of CA3pcs will be examined in response to systematic combinations of excitatory inputs. Surgically and pharmacologically isolated pathways will be stimulated extracellularly at various intensities and frequencies, while recording from individual CA3pcs. Corresponding compartmental simulations, implemented and validated against the experiments, will extensively characterize the computational properties of CA3pcs with respect to non-linear summation, pathway specificity, and coincidence detection of synaptic input. The public health relevance of this project directly relates to the mission of the NIA. Malfunction of the hippocampus is linked to devastating age-related conditions such as Alzheimer's disease. The combination of state-of-the-art experimental techniques with the ever-increasing computational power of biophysical modeling will accelerate research progress and help develop highly trained neuroscientists. In addition to the dissemination of results in conferences and peer-reviewed publications, all models will be publicly distributed through internet archives.

描述（申请人提供）：CA3锥体细胞（CA3pcs）构成海马突触整合的中心十字路口，在空间映射和记忆存储中发挥关键作用。 CA3 细胞受到内嗅皮层、齿状颗粒细胞和其他 CA3 细胞的单突触兴奋。 CA3pcs 的电生理功能包括单次尖峰和爆发，跨越很宽的频率范围。尽管人们对 CA3pcs 的解剖学和生理学有了一般性的了解，但对于给定的突触输入模式与最终的放电输出之间的对应关系却知之甚少。这些信息对于关联海马活动和功能至关重要，构成了该项目的主要目标。首先，我们将研究 CA3pc 树突生物物理学（被动特性、通道分布和动力学）以及每个通路的单一突触输入。这将通过电压和电流钳记录、钙成像以及创建详细的数据驱动计算模型来实现。接下来，将检查 CA3pcs 响应兴奋性输入的系统组合的放电模式。手术和药理学分离的途径将以不同的强度和频率在细胞外受到刺激，同时从单个 CA3pcs 进行记录。通过实验实施和验证的相应区室模拟将广泛表征 CA3pcs 在非线性求和、通路特异性和突触输入的重合检测方面的计算特性。该项目的公共卫生相关性与 NIA 的使命直接相关。海马体功能障碍与阿尔茨海默病等破坏性年龄相关疾病有关。最先进的实验技术与生物物理模型不断增强的计算能力的结合将加速研究进展并帮助培养训练有素的神经科学家。除了在会议和同行评审出版物中传播结果外，所有模型都将通过互联网档案公开发布。