CRCNS: Phase resetting predicts synchronization in hybrid hippocampal circuits

CRCNS：相位重置预测混合海马回路的同步

• 批准号: 7677250
• 负责人: Carmen Castro Canavier
• 金额: $ 31.13万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-20 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7677250
• 关键词: Behavior; Biological; Brain; Cells; Coupling; Distal; Distant; Female; Frequencies; Heterogeneity; Hippocampus (Brain); Hybrids; Individual; Interneurons; Lead; Measurement; Mediating; Myoepithelial cell; Neurons; Phase; Play; Principal Investigator; Property; Pyramidal Cells; Role; Simulate; Techniques; Testing; Theta Rhythm; Time; Training; Underrepresented Minority; Work; base; cognitive function; novel; novel strategies; relating to nervous system; research study; response

DESCRIPTION (provided by applicant): Theta (4-12 Hz) and gamma (30-80 Hz) oscillations in the hippocampus are likely to be substrates for critical cognitive functions. To play such a role, the theta and gamma rhythms must be coherent across long distances (mm or more) in the brain. The mechanisms that lead to synchronization within and between local circuits separated by conduction delays are poorly understood. In the proposed work, two lab groups will collaborate to apply novel theoretical concepts of local and long-distance synchronization in electrophysiological experiments. Using the dynamic clamp technique, hippocampal microcircuits, containing biological and computationally simulated neurons that interact in real time, will be constructed. Together, the proposed theoretical and experimental studies will test the hypothesis that short- and long-range synchronization can be understood using the properties of mathematical symmetry and phase resetting properties of individual neurons and specific local neuronal microcircuits. We hypothesize that the phase resetting curves of the oscillatory neural modules contain all the information necessary to predict synchronization behavior, that synchronization between distal modules is based on symmetry between oscillators with similar frequencies, that in the presence of sufficiently strong coupling the symmetric mechanism is robust to biological levels of heterogeneity, and that harmonic locking between theta and gamma rhythms may play an important role in oscillatory coherence. Specific Aim 1. Test the hypothesis that synchronization of distal gamma modules mediated by long range excitatory connections results from near-symmetry (i.e., similar intrinsic frequencies and inter-module conduction delays) and preferential synchronization among similar distal modules. We will test theoretical predictions of synchronization based on phase resetting curves using gamma modules containing pyramidal cells and fast-spiking basket cell interneurons. Specific Aim 2. Test the hypothesis that N:1 locking between the gamma and theta rhythm aligns the firing of local oriens-lacunosum moleculare (O-LM) interneurons with that of a gamma cycle, with a fixed number of missed gamma cycles between theta cycles. Existence and stability conditions for N:1 locking based on the phase resetting curves will be used to predict when such locking occur. We will also determine whether N:1 locking can be sufficient to synchronize multiple O-LM interneurons within a local module, or if common external perturbations in the presence of such locking are required to promote theta coherence within local circuits. Predictions from phase-response measurements will be tested in hybrid microcircuits representing distant local circuits. Specific Aim 3. Test the hypothesis that synchronization of distal gamma modules mediated by O-LM interneurons firing at theta frequency also emerges as a consequence of near symmetry. In the case of synchronized O-LM cells, this extension is straightforward, but in practice, synchronization between O-LM cells is not required. We will test theoretical predictions of synchronization based on phase resetting curves using gamma modules connected via O-LM interneurons. Intellectual Merit: A novel approach to the highly significant question of how neural oscillators can synchronize their activity, particularly in the presence of conduction delays, is presented here. The theoretical and experimental aspects of the proposal are integrated in a synergistic way. Broader Impacts: There is a significant and highly interdisciplinary training component of this project at the undergraduate (B. Bullock, M. Woodman), graduate and postgraduate levels. With respect to diversity, at least one of the principal trainees will be an underrepresented minority and one principal investigator is female.

描述（由申请人提供）：海马体中的 Theta（4-12 Hz）和 gamma（30-80 Hz）振荡可能是关键认知功能的基础。为了发挥这样的作用，theta 和 gamma 节律必须在大脑中长距离（毫米或更长）上保持一致。人们对导致由传导延迟分隔的本地电路内部和之间的同步的机制知之甚少。在拟议的工作中，两个实验室小组将合作在电生理学实验中应用局部和长距离同步的新理论概念。使用动态钳技术，将构建包含实时相互作用的生物和计算模拟神经元的海马微电路。所提出的理论和实验研究将共同​​检验这样的假设：利用单个神经元和特定局部神经元微电路的数学对称性和相位重置特性可以理解短程和长程同步。我们假设振荡神经模块的相位重置曲线包含预测同步行为所需的所有信息，远端模块之间的同步基于具有相似频率的振荡器之间的对称性，在存在足够强的耦合的情况下，对称机制是鲁棒的到生物水平的异质性，θ 节律和伽马节律之间的谐波锁定可能在振荡相干性中发挥重要作用。具体目标 1. 检验以下假设：由长程兴奋性连接介导的远端伽马模块的同步是由近对称性（即相似的固有频率和模块间传导延迟）和相似远端模块之间的优先同步引起的。我们将使用包含锥体细胞和快速尖峰篮状细胞中间神经元的伽玛模块来测试基于相位重置曲线的同步理论预测。具体目标 2. 测试假设，伽马节律和 θ 节律之间的 N:1 锁定使局部东方-腔隙分子 (O-LM) 中间神经元的放电与伽马周期的放电一致，并且 θ 之间错过固定数量的伽马周期循环。基于相位重置曲线的 N:1 锁定的存在和稳定性条件将用于预测何时发生这种锁定。我们还将确定 N:1 锁定是否足以同步本地模块内的多个 O-LM 中间神经元，或者是否需要在存在此类锁定的情况下进行常见的外部扰动来促进本地电路内的 theta 一致性。相位响应测量的预测将在代表远程本地电路的混合微电路中进行测试。具体目标 3. 测试以下假设：由以 theta 频率发射的 O-LM 中间神经元介导的远端伽马模块的同步也是近对称性的结果。在同步O-LM单元的情况下，这种扩展很简单，但实际上，不需要O-LM单元之间的同步。我们将使用通过 O-LM 中间神经元连接的伽玛模块来测试基于相位重置曲线的同步理论预测。智力优点：本文提出了一种新颖的方法来解决神经振荡器如何同步其活动（特别是在存在传导延迟的情况下）这一非常重要的问题。该提案的理论和实验方面以协同方式整合在一起。更广泛的影响：该项目在本科生（B. Bullock、M. Woodman）、研究生和研究生水平上有一个重要且高度跨学科的培训组成部分。在多样性方面，至少一名主要受训者将是代表性不足的少数群体，一名主要研究员是女性。