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赫兹)和伽马(30-80赫兹)振荡很可能是关键认知功能的底物。为了发挥这样的作用，在大脑中，theta和Gamma节律必须在很长的距离(毫米或更长)上保持一致。由导通延迟隔开的局部电路内和局部电路之间导致同步的机制知之甚少。在这项拟议的工作中，两个实验室小组将合作将本地和远程同步的新理论概念应用于电生理实验。利用动态钳制技术，将构建包含生物和计算模拟神经元的海马微电路，这些神经元实时相互作用。总之，拟议的理论和实验研究将检验这一假设，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是基于相似频率的振荡器之间的对称性，在足够强的耦合存在下，对称机制对生物水平的异质性是健壮的，以及theta和Gamma节律之间的谐波锁定可能在振荡相干性中发挥重要作用。具体目的1.检验远端伽玛模块之间的同步是由于相似的固有频率和模块间的传导延迟以及相似远端模块之间的优先同步所致。我们将使用包含锥体细胞和快速尖峰篮子细胞中间神经元的伽马模块来测试基于相位重置曲线的同步理论预测。具体目的2.检验这样的假设，即伽马和theta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，在theta周期之间错失伽马周期的固定数量。基于相位重置曲线的N：1闭锁的存在条件和稳定性条件将被用来预测何时发生这种闭锁。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，或者是否需要在存在此类锁定的情况下进行共同的外部扰动以促进局部电路内的theta一致性。来自相位响应测量的预测将在代表远距离本地电路的混合微电路中进行测试。具体目的3.验证这样一种假设，即O-Lm中间神经元以theta频率放电所介导的远端伽马模块的同步也是近对称的结果。在同步O-LM信元的情况下，这种扩展是直接的，但在实践中，O-LM信元之间的同步不是必需的。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的理论预测。智力价值：这里提出了一种新的方法来解决神经振荡器如何同步它们的活动这一非常重要的问题，特别是在存在传导延迟的情况下。该提案的理论和实验方面以协同的方式整合在一起。更广泛的影响：在本科生(B.Bullock，M.Woodman)、研究生和研究生阶段，该项目有一个重要的、高度跨学科的培训部分。关于多样性，至少有一名主要受训人员将是代表人数不足的少数群体，一名首席调查员是女性。