CRCNS: Analysis of synchronization in hybrid neural circuits

描述（由申请人提供）：所提出的工作的目标是建立一个基于相位重置曲线（PRC）的理论框架，用于理解生物神经元网络中同步和锁相的基本机制。这些现象是产生重复运动活动（如运动和呼吸）的中枢模式的基础。神经元的瞬时同步组装被假设为许多认知功能的基础，并且同步在精神疾病如精神分裂症中被改变。病理性同步与癫痫和震颤有关。PRC测量由于对隔离神经元的输入扰动而导致的周期性循环的长度的变化，并且提供关于网络上下文内的神经元的活动的有用信息。在之前的进展期间，探索了两种主要方法作为理论基础：1：在脉动耦合假设下使用尖峰（或爆发）作为扰动的相位重置曲线和2）功能PRC（FPRC），其由在每次尖峰（或爆发）启动后的固定延迟处施加类似扰动的重复刺激组成。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中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，不是固有振荡器的神经元，噪声电路，以及无法为每个组成神经元详细定义参数的电路。以下目标将在下一个项目期间完成：我们将开发和测试基于PRC的方法，包括非内源性起搏器的神经元，分析适应神经元的电路，并估计在噪声和异质性存在下同步的鲁棒性。我们将使用我们开发的方法分析生物中枢模式发生器，龙虾和螃蟹的幽门回路。一般原则将出现，应该适用于许多振荡网络的神经系统。更好地理解这些机制将提供工具，以确定同步是如何出错的神经系统疾病，如癫痫和震颤，或在精神疾病，其中认知受损。 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。生物神经元的网络可以自发地产生模式化的活动，这些活动是有节奏的重复运动行为（如呼吸和运动）的基础，并且皮质网络中的瞬时同步被假设为介导认知功能，如注意力，感知以及信息存储和检索。更好地理解这些机制将提供工具，以确定同步是如何出错的神经系统疾病，如癫痫和震颤，或在精神疾病，其中认知受损。

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.