Information flow in the limbic theta circuit revealed by Granger causality

格兰杰因果关系揭示的边缘西塔回路中的信息流

• 批准号: 7991049
• 负责人: BERNAT KOCSIS
• 金额: $ 24.28万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-15 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7991049
• 关键词: Address; Affect; Anesthesia procedures; Attention; Automobile Driving; Behavior; Categories; Cell Nucleus; Cell physiology; Characteristics; Effectiveness; Electric Stimulation; Electroencephalography; Etiology; Exhibits; Exploratory/Developmental Grant; Frequencies; Generations; Goals; Hand; Hippocampus (Brain); Investigation; Knowledge; Lesion; Medial; Methods; Motor; Movement; Neurons; Neurosciences Research; Pathway interactions; Pattern; Perforant Pathway; Pharmacology; Phase; Play; REM Sleep; Rattus; Role; Running; Sensory; Signal Transduction; Sleep; Source; Speed; Stimulus; Structure; System; Techniques; Testing; Training; Variant; awake; base; falls; hippocampal fissure; neural circuit; public health relevance; research study; septohippocampal; tool

DESCRIPTION (provided by applicant): Theta behaviors in the hippocampus fall in several categories, e.g. movement related (Type 1), immobility related (Type 2), and REM sleep theta, with distinct layer specific current source distributions, different pharmacological features, and characteristic frequencies. The mechanism of the generation of theta at different frequencies is poorly understood but its strong association with different aspects of behavior (sensory-motor integration, sleep, etc.) indicates that subcortical structures play an essential role. A number of subcortical nuclei exhibit theta rhythmic neuronal activity synchronized with hippocampal oscillations and our goal is to identify the functional relationship among these structures and rhythmic activity in the hippocampus. The commonly used symmetrical methods of signal analysis have limited utilities in this regard as they could not provide information on causal influences. Thus the goal of the present R21 is to test the effectiveness of a newly proposed method called Granger causality on two subcortical structures generating theta in the hippocampus: medial septum (MS) and supramammillary nucleus (SUM). First (Specific Aim 1), we will validate the method in the context of the hippocampal network in two experiments; one in which the causal direction is known (using stimulation of input pathways and recording field potentials in their target layers of the hippocampus) and the other in which the causal direction comes from prior knowledge of the information flow along the classic hippocampal "three-synaptic circuit". Then, in Specific Aim 2, we will address the causal influence and directional driving of hippocampal theta by subcortical theta generators (SUM and MS) and test whether Granger causality can be a tool in hypothesis-driven investigation of this system. We hypothesize, in particular, that SUM involvement is limited to specific states, and thus expect to find significant directional drive from SUM to hippocampus associated with fast theta during waking exploration and phasic episodes of REM sleep but not during slow theta of waking immobility, and tonic REM sleep. On the other hand, we hypothesize that MS, providing a final common pathway for ascending drives from different sources, will show significant directional drive to the hippocampus in all theta states. PUBLIC HEALTH RELEVANCE: The mechanism of the generation of theta at different frequencies is poorly understood but its strong association with different aspects of behavior indicates that subcortical structures play an essential role. The goal of the present R21 is to test the effectiveness of a newly proposed method called Granger causality on two subcortical structures: medial septum (MS) and supramammillary nucleus (SUM).

描述（由申请人提供）：海马体中的 Theta 行为分为几类，例如运动相关（类型 1）、不动相关（类型 2）和 REM 睡眠 θ，具有不同的层特定电流源分布、不同的药理学特征和特征频率。人们对不同频率的 θ 产生机制知之甚少，但它与行为的不同方面（感觉运动整合、睡眠等）的密切相关表明皮层下结构发挥着重要作用。许多皮质下核表现出与海马振荡同步的θ节律神经元活动，我们的目标是确定这些结构与海马节律活动之间的功能关系。常用的信号分析对称方法在这方面的实用性有限，因为它们无法提供有关因果影响的信息。因此，当前 R21 的目标是测试新提出的称为 Granger 因果关系的方法对海马中生成 theta 的两个皮层下结构的有效性：内侧隔 (MS) 和乳头上核 (SUM)。首先（具体目标 1），我们将在两个实验中在海马网络的背景下验证该方法；一种是已知因果方向（使用输入通路的刺激并记录海马目标层的场电位），另一种是因果方向来自沿经典海马“三突触”信息流的先验知识电路”。然后，在具体目标 2 中，我们将通过皮层下 θ 发生器（SUM 和 MS）解决海马 θ 的因果影响和定向驱动，并测试格兰杰因果关系是否可以成为该系统的假设驱动研究的工具。我们特别假设 SUM 参与仅限于特定状态，因此期望在清醒探索和 REM 睡眠阶段性发作期间找到与快速 θ 相关的从 SUM 到海马的显着定向驱动，但在清醒不动的慢 θ 期间则不然，并且快速眼动睡眠。另一方面，我们假设 MS 为来自不同来源的上升驱动力提供了最终的共同路径，将在所有 θ 状态下显示出对海马体的显着定向驱动力。 公共健康相关性：人们对不同频率的 θ 产生机制知之甚少，但它与不同行为方面的密切关联表明皮层下结构发挥着重要作用。目前 R21 的目标是测试新提出的格兰杰因果关系方法对两种皮质下结构的有效性：内侧隔膜 (MS) 和乳头上核 (SUM)。