CRCNS: Analysis of synchronization in hybrid neural circuits

描述(申请人提供)：拟议工作的目标是建立一个基于相位重置曲线(PRC)的理论框架，以了解生物神经元网络中同步和相位锁定的基本机制。这些现象是产生重复运动活动，如运动和呼吸的中心模式产生的基础。瞬时同步的神经元集合被认为是许多认知功能的基础，而在精神分裂症等精神障碍中，同步会发生变化。癫痫和震颤与病理性同步性有关。PRCS测量由于对孤立神经元的输入扰动而导致的周期周期长度的变化，并提供关于网络环境中神经元活动的有用信息。在之前的进展阶段，两种主要的方法被探索作为理论的基础：1)在脉动耦合的假设下使用尖峰(或短脉冲)作为扰动的相位重置曲线；2)在每次尖峰(或短脉冲)启动后以固定延迟施加类似扰动的由重复刺激组成的功能PRC(FPRC)。该项目的总体目标是创建一个非常广泛的理论框架，可用于分析神经系统协调振荡活动的生物学基础。因此，我们需要开发和测试方法来分析电路，包括表现出尖峰频率适应的神经元、非本征振荡器的神经元、噪声电路以及其参数不能为每个组件神经元详细定义的电路。我们将在下一个项目期间完成以下目标：我们将开发和测试基于PRC的方法，以包括非内源性起搏器的神经元，分析适应神经元的电路，并评估在存在噪声和异质性存在的情况下同步的稳健性。我们将使用我们开发的方法来分析生物中枢模式生成器，龙虾和螃蟹的幽门回路。将会出现适用于神经系统中许多振荡网络的一般原理。更好地了解这些机制将提供工具，以确定在癫痫和震颤等神经疾病中，或在认知受损的精神障碍中，同步是如何出错的。 公共卫生相关性：这项工作的目的是了解神经系统中同步和模式形成的基本机制。生物神经元网络可以自发地产生有模式的活动，这些活动是有节奏的、重复的运动行为(如呼吸和运动)的基础，皮质网络中的瞬时同步被假设为调节诸如注意力、感知以及信息存储和检索等认知功能。更好地了解这些机制将提供工具，以确定在癫痫和震颤等神经疾病中，或在认知受损的精神障碍中，同步是如何出错的。

DESCRIPTION (provided by applicant): The goal of the proposed work is to build a theoretical framework based on phase resetting curves (PRC) for understanding the basic mechanisms of synchronization and phase locking in networks of biological neurons. These phenomena underlie central pattern generation for the production of repetitive motor activity such as locomotion and respiration. Transiently synchronized assemblies of neurons are hypothesized to underlie many cognitive functions, and synchronization is altered in psychiatric disorders such as schizophrenia. Pathological synchronization is involved in epilepsy and tremor. PRCs measure the change in length of a periodic cycle due to an input perturbation to an isolated neuron, and provide useful information regarding the activity of the neuron within a network context. During the previous progress period, two major approaches were explored as theoretical substrates: 1: the phase resetting curves using a spike (or burst) as a perturbation under the assumption of pulsatile coupling and 2) a functional PRC (FPRC) consisting of repeated stimulation with a similar perturbation applied at a fixed delay after each spike (or burst) initiation. The overall goal of the project is to create a very broad theoretical framework that can be used to analyze the biological basis of coordinated oscillatory activity in the nervous system. Therefore we need to develop and test methods to analyze circuits that include neurons exhibiting spike frequency adaptation, neurons that are not intrinsic oscillators, noisy circuits, and circuits whose parameters cannot be defined in detail for every component neuron. The following objectives will be accomplished in the next project period: we will develop and test PRC-based methods to include neurons that are not endogenous pacemakers, to analyze circuits of adapting neurons, and to estimate the robustness of synchronization in the presence of noise and heterogeneity. We will analyze a biological central pattern generator, the pyloric circuit of the lobster and crab, using the methods that we develop. General principles will emerge that should be applicable to many oscillatory networks in the nervous system. A better understanding of these mechanisms will provide tools to determine how synchronization goes awry in neurological disorders such as epilepsy and tremor, or in psychiatric disorders in which cognition is impaired. PUBLIC HEALTH RELEVANCE: The purpose of this work is to understand basic mechanisms of synchronization and pattern formation in the nervous system. Networks of biological neurons can spontaneously generate patterned activity that underlies rhythmic, repetitive motor behaviors such as respiration and locomotion, and transient synchronization in cortical networks is hypothesized to mediate cognitive functions such as attention, perception, and information storage and retrieval. A better understanding of these mechanisms will provide tools to determine how synchronization goes awry in neurological disorders such as epilepsy and tremor, or in psychiatric disorders in which cognition is impaired.