Mechanisms of Persistence in Head Direction Cells

头部方向细胞的持久性机制

• 批准号: 6877139
• 负责人: ANTON N KHABBAZ
• 金额: $ 12.54万
• 依托单位: PRINCETON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6877139
• 关键词: NMDA receptors; action potentials; behavioral /social science research tag; brain electrical activity; brain mapping; central neural pathway /tract; computational neuroscience; genetically modified animals; head movements; laboratory mouse; microelectrodes; neural information processing; orientation; proprioception /kinesthesia; sensory signal detection; space perception; tegmentum; thalamic nuclei

DESCRIPTION (provided by applicant): This project will capitalize on novel microelectrode recording technology and the unique advantages of the transgenic mouse system to study persistent neural activity. Head Direction (HD) cells, the circuit studied, integrate ideothetic cues such as angular head velocity to provide a neural firing pattern that represents head direction in the lab frame of reference. Because the activity remains when sensory inputs are restricted, the activity has the characteristics of a short term memory. Neural network models describe this system, using a framework pioneered by Hopfield, as a continuous attractor driven by net positive feedback based on recurrent excitation. The research objective is to measure the network and cellular mechanisms underlying persistent neural activity in the HD system, relating these properties to recurrent network models. Now a novel recording method developed here can relate for the first time the firing properties of multiple single HD cells in the same small nucleus of awake and behaving mice, where each of up to five individually adjustable electrodes can simultaneously record an isolated single neural unit. This device allows measurement of the persistence time of the network and the timing relationship between similarly tuned HD cells. Developing this mouse recording system allows us to use genetics to overexpress or delete important ion channels and receptors for this system such as the N-methyI-D-aspartate receptor. This work will combine in vivo electrophysiology, transgenic technologies, pharmacology, viral infusions and other methods to manipulate and measure the system to reveal its properties. The work will be a collaboration between the labs of Drs. Tank and Tsien at Princeton University and consultant Dr. J. S. Taube. This project has broad significance for neuroscience for two reasons. Firstly, the electrode method development here is the first to allow measurement of multiple single neurons in any small nucleus of a mouse, and should find applicability by other laboratories studying other neural systems. Recording methods for mice will become even more crucial as transgenic mouse technologies advance. Secondly, the continuous attractor model studied here for HD cells has also been proposed for a variety of other systems, so the cellular and network mechanisms elucidated here could very well apply to short-term memory in general.

描述（由申请人提供）：该项目将利用新颖的微电极记录技术以及转基因小鼠系统的独特优势，以研究持续的神经活动。研究电路的头部方向（HD）细胞整合了视力线索，例如角头速度，以提供一种神经射击模式，该模式代表实验室参考框架中的头部方向。由于在限制感觉输入时，活动仍然存在，因此该活动具有短期内存的特征。神经网络模型使用霍普菲尔德（Hopfield）开创的框架描述了该系统，它是一种由基于复发激发的净正反馈驱动的连续吸引子。研究目标是测量HD系统中持续神经活动的网络和细胞机制，将这些属性与经常性网络模型有关。现在，此处开发的一种新颖的记录方法可以首次与同一小核和行为小鼠相同的小核中多个单个HD细胞的发射特性有关，其中最多五个单独调节的电极都可以同时记录一个孤立的单个神经单位。该设备允许测量网络的持续时间和类似调谐的HD单元之间的时机关系。开发这种小鼠记录系统使我们能够使用遗传学过表达或删除该系统（例如N-Methyi-D-天冬氨酸受体）的重要离子通道和受体。这项工作将结合体内电生理学，转基因技术，药理学，病毒输注和其他操纵和测量系统以揭示其性质的方法。这项工作将是DRS实验室之间的合作。普林斯顿大学的坦克和Tsien和J. S. Taube博士。该项目对神经科学具有广泛的意义，原因有两个。首先，这里的电极方法开发是第一个允许在小鼠的任何小核中测量多个单个神经元的方法，并且应该找到其他研究其他神经系统的实验室的适用性。随着转基因小鼠技术的发展，小鼠的记录方法将变得更加重要。其次，在此处研究的HD细胞的连续吸引子模型也针对其他各种系统提出了，因此此处阐明的细胞和网络机制通常适用于通常适用于短期记忆。