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- 12hz）和gamma （30- 80hz）振荡可能是关键认知功能的基础。要发挥这样的作用，θ和γ节律必须在大脑中长距离（毫米或更长）保持一致。导致由传导延迟分隔的局部电路内部和之间同步的机制尚不清楚。在拟议的工作中，两个实验室小组将合作在电生理实验中应用本地和远程同步的新理论概念。利用动态钳技术，海马体微电路，包括生物和计算模拟的神经元，实时相互作用，将被构建。总之，提出的理论和实验研究将验证这样一个假设，即可以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来理解短期和远程同步。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是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，对称机制对生物水平的异质性具有鲁棒性。和节奏之间的谐波锁定可能在振荡相干性中发挥重要作用。具体目标验证远程兴奋连接介导的远端伽马模块的同步是由近对称（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假设。我们将测试基于相位重置曲线的同步理论预测，使用包含锥体细胞和快速尖峰篮细胞中间神经元的伽马模块。具体目标2。测试假设，在伽马和θ节律之间的N:1锁定使局部定向-空白分子（O-LM）中间神经元的放电与伽马周期一致，在θ周期之间有固定数量的遗漏伽马周期。基于相位重置曲线的N:1锁定的存在性和稳定性条件将用于预测这种锁定何时发生。我们还将确定N:1锁定是否足以同步局部模块内的多个O-LM中间神经元，或者是否需要在这种锁定存在下的常见外部扰动来促进局部电路内的θ相干性。相位响应测量的预测将在代表遥远局部电路的混合微电路中进行测试。具体目标3。验证由O-LM中间神经元以θ频率放电介导的远端伽马模块同步也作为接近对称的结果出现的假设。在同步的O-LM单元的情况下，这个扩展很简单，但在实践中，O-LM单元之间的同步是不需要的。我们将使用通过O-LM中间神经元连接的伽马模块来测试基于相位重置曲线的同步理论预测。智力优势：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这一高度重要的问题，特别是在传导延迟的情况下。该建议的理论和实验方面以一种协同的方式相结合。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的、高度跨学科的培训组成部分。在多样性方面，至少有一名主要受训者是代表性不足的少数民族，一名主要研究员是女性。