CRCNS: Path Intergration by the Grid Cell Network

描述（由申请人提供）：自从有可能测量神经系统中的电活动以来，人们就知道大脑产生振荡节律。有些节奏是在睡眠时产生的，有些是在清醒时产生的；某些模式的振荡大脑活动发生在所有健康的人，而其他模式只发生在疾病状态，如癫痫，临床抑郁症，或精神分裂症。许多不同的大脑节律已经被识别和表征，但对它们的功能几乎一无所知。我们知道大脑振荡，但我们不知道为什么。在过去的几年里，一些发现为回答这个问题提供了诱人的新线索，这些发现表明，神经振荡非常像大脑编织在一起的“线”，形成了记忆和感知的“织物”。在老鼠身上，一种被称为“θ节律”的特殊振荡在海马体和内嗅皮层中非常重要，这两个大脑区域在学习和记忆中起着至关重要的作用。越来越清楚的是，θ波振荡（在4-12赫兹频带内）是海马体和内嗅皮层构建记忆表征的基石。这里提出的研究将结合神经生理学记录实验和计算建模研究来研究大鼠的大脑如何利用θ波振荡来形成对空间中熟悉位置的记忆。被称为“位置细胞”和“网格细胞”的神经元在老鼠访问某些熟悉的位置时变得活跃，这些神经元与θ波振荡强烈同步。拟议的计算建模研究将调查位置细胞和网格细胞如何使用θ振荡来编码空间记忆，并将寻求破译执行这项任务的生物神经网络的结构。拟议的神经生理学研究将首次尝试表明，皮层下区域的神经振荡器使用“相位编码”存储记忆表征，并将研究大脑皮层如何与皮层下振荡器相互作用以读出这些记忆表征。将进行药物失活研究，以证明当神经振荡被破坏时，记忆处理是如何中断的，这可能有助于解释那些患有阿尔茨海默病、精神分裂症、抑郁症、焦虑症和创伤后应激障碍等失忆症综合征的人的记忆障碍的原因。通过阐明空间记忆回路中的θ波振荡是如何形成记忆的，本研究将为神经振荡在正常记忆过程中所起的基本作用提供开创性的新见解。这项工作可能在未来使诊断和治疗目前尚不清楚的脑部疾病和精神障碍成为可能，但可能证明其根源在于为记忆和感知提供基本构建块的神经振荡器功能障碍。

DESCRIPTION (provided by applicant): For as long as it has been possible to measure electrical activity in the nervous system, it has been known that the brain produces oscillatory rhythms. Some rhythms are generated during sleep, others during waking; certain patterns of oscillatory brain activity occur in all healthy people, while other patterns only occur in disease states such as epilepsy, clinical depression, or schizophrenia. Many different brain rhythms have been identified and characterized, and yet almost nothing is known about their function. We know that the brain oscillates, but we do not know why. Over the past few years, discoveries have been made that provide tantalizing new clues for answering this question, by suggesting that neural oscillations are very much like "threads" that the brain weaves together to create the "fabric" of memory and perception. In rats, one particular kind of oscillation referred to as "theta rhythm" is very predominant in the hippocampus and entorhinal cortex, brain areas that play a critical role in learning and memory. It is becoming increasingly clear that theta oscillations (in the frequency band of 4-12 Hz) are building blocks from which the hippocampus and entorhinal cortex can construct memory representations. The studies proposed here will combine neurophysiological recording experiments with computational modeling studies to investigate how the rat brain uses theta oscillations to form memories of familiar locations in space. Neurons called "place cells" and "grid cells" become active whenever a rat visits certain familiar locations, and these neurons are strongly synchronized by theta oscillations. Proposed computational modeling studies will investigate how place cells and grid cells use theta oscillations to encode spatial memories, and will seek to decipher the structure of the biological neural networks that perform this task. Proposed neurophysiology studies will attempt to show for the first time that neural oscillators in subcortical regions store memory representations using a "phase code," and will examine how the cerebral cortex interacts with subcortical oscillators to read out these memory representations. Pharmacological inactivation studies will be conducted to demonstrate how memory processing breaks down when neural oscillators are disrupted, which may help to explain the causes of memory impairment in humans who suffer from amnesic syndrome in conjunction with disorders like Alzheimer's disease, schizophrenia, depression, anxiety disorders, and post-traumatic stress. By elucidating how memories are formed from theta oscillations in spatial memory circuits, the research proposed here will provide groundbreaking new insights into the fundamental role that neural oscillations play in normal memory processes. This work may in the future make it possible to diagnose and treat brain diseases and mental disorders that currently are not well understood, but which may prove to have roots in dysfunction of the neural oscillators that provide the basic building blocks for memory and perception.