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）：海马中的Theta（4-12 Hz）和伽马（30-80 Hz）振荡可能是关键认知功能的底物。要扮演这样的角色，theta和γ节奏必须在大脑中的长距离（MM或更多）上相干。鲜为人知的是导致导致在传导延迟分离的局部电路内和之间同步的机制。在拟议的工作中，两个实验室组将在电生理实验中运用局部和长距离同步的新理论概念。将使用动态夹具技术，将构建具有实时相互作用的生物学和计算模拟神经元的海马微电路。总之，提出的理论和实验研究将检验以下假设：可以使用数学对称性的特性和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。我们假设振荡性神经模块的相位重置曲线包含预测同步行为所必需的所有信息，即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，即在相似频率的振荡器之间，即在足够强大的对称机制之间存在足够强大的对称机制，并且是良好的态度锁定的，并且是良好的态度锁定的，那是循环量的稳固型，这是圆锥量的态度锁定的，既有预域，又可能是循环系统的，在振荡一致性中的重要作用。具体目的1。检验以下假设：远程兴奋性连接介导的远端伽马模块的同步是由近对称性（即相似的内在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。我们将使用含有锥体细胞和快速加速篮细胞中间神经元的伽马模块基于相位重置曲线来测试同步的理论预测。具体目的2。检验以下假设：gam和theta节奏之间的n：1锁定是对局部oriens-lacunosum moleculare（O-LM）中间神经元与伽马循环的触发的触发，并与Theta Cycles之间的固定数量的Gamma循环相结合。基于相位重置曲线的N：1锁定的存在和稳定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中的多个O-LM中间神经元，还是需要在存在这种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相干性。相应测量值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。检验以下假设：近对称性近对称性的theta频率O-LM中间神经元介导的远端伽马模块的同步也出现了。在同步的O-LM细胞的情况下，该扩展很简单，但实际上，不需要O-LM细胞之间的同步。我们将使用通过O-LM中间神经元连接的γ模块基于相位重置曲线的同步测试理论预测。智力优点：在这里提出了一种新的方法，即神经振荡器如何同步其活动，尤其是在传导延迟的情况下，这是一种新颖的方法。该提案的理论和实验方面以协同的方式整合。更广泛的影响：该项目的本科生（B. Bullock，M。Woodman），研究生和研究生水平有一个重要且高度的跨学科培训部分。关于多样性，至少一名主要学员将是代表性不足的少数派，而一名首席研究员是女性。