Mechanisms of Persistence in Head Direction Cells

描述（由申请人提供）：本项目将利用新型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的神经活动。头部方向（HD）细胞，电路研究，整合意识形态线索，如角头部速度提供神经放电模式，代表头部方向在实验室的参考框架。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首创的框架将该系统描述为一个由基于循环激励的净正反馈驱动的连续吸引子。研究目的是测量HD系统中持续神经活动的网络和细胞机制，并将这些特性与循环网络模型联系起来。现在，这里开发的一种新的记录方法首次将清醒和行为小鼠的同一个小核中多个单个HD细胞的放电特性联系起来，其中多达五个单独可调节的电极中的每一个都可以同时记录一个孤立的单个神经单元。该设备允许测量网络的持续时间和类似调优的高清单元之间的时序关系。开发这种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。本工作将结合体内电生理学、转基因技术、药理学、病毒输注等方法对该系统进行操作和测量，揭示其特性。这项工作将由两位博士的实验室合作完成。普林斯顿大学的Tank和Tsien以及顾问J. S. Taube博士。该项目对神经科学具有广泛意义，原因有二。首先，电极方法的发展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，并且应该在研究其他神经系统的其他实验室中找到适用性。随着转基因小鼠技术的进步，小鼠的记录方法将变得更加重要。其次，这里研究的HD细胞的连续吸引子模型也被提出用于各种其他系统，因此这里阐明的细胞和网络机制可以很好地应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.