Mechanisms of Persistence in Head Direction Cells

描述(申请人提供)：该项目将利用新的微电极记录技术和转基因小鼠系统的独特优势来研究持续神经活动。该电路研究的头部方向(HD)细胞，整合了理想化的线索，如头部的角速度，以提供在实验室参照系中代表头部方向的神经放电模式。因为当感觉输入受到限制时，这种活动仍然存在，所以这种活动具有短期记忆的特征。神经网络模型使用Hopfield提出的框架，将该系统描述为一个基于循环激励的网络正反馈驱动的连续吸引子。研究的目的是测量HD系统中持续神经活动的网络和细胞机制，将这些特性与递归网络模型联系起来。现在，这里开发的一种新的记录方法可以首次与清醒和行为小鼠同一小核中多个单个HD细胞的放电特性有关，其中最多五个单独可调的电极中的每个可以同时记录一个孤立的单个神经元单位。该设备允许测量网络的持续时间和类似调谐的HD小区之间的定时关系。开发这一小鼠记录系统使我们能够利用遗传学来过度表达或删除该系统的重要离子通道和受体，如N-甲基-D-天冬氨酸受体。这项工作将结合体内电生理学、转基因技术、药理学、病毒注射等方法来操纵和测量该系统，以揭示其特性。这项工作将由普林斯顿大学的坦克和钱存训博士的实验室以及顾问J·S·陶贝博士共同完成。这个项目对神经科学具有广泛的意义，原因有两个。首先，这里开发的电极方法是第一个允许测量小鼠任何小核中的多个单个神经元的方法，应该可以适用于其他研究其他神经系统的实验室。随着转基因小鼠技术的进步，小鼠的记录方法将变得更加关键。其次，这里研究的HD细胞的连续吸引子模型也被提出用于其他各种系统，因此这里阐明的细胞和网络机制可以很好地适用于一般的短期记忆。

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.