Information flow in the limbic theta circuit revealed by Granger causality

描述（由申请人提供）：海马体中的θ行为分为几类，例如运动相关（1型）、不动相关（2型）和REM睡眠θ，具有不同的层特异性电流源分布、不同的药理学特征和特征频率。在不同频率下产生θ波的机制知之甚少，但它与行为的不同方面（感觉运动整合，睡眠等）有很强的联系。表明皮层下结构起着至关重要的作用一些皮层下核团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和海马节律活动之间的功能关系。常用的对称信号分析方法在这方面的效用有限，因为它们不能提供有关因果影响的信息。因此，目前的R21的目标是测试的有效性，一个新提出的方法称为格兰杰因果关系的两个皮层下结构产生θ在海马：内侧隔（MS）和乳头体上核（SUM）。首先（具体目标1），我们将在两个实验中的海马网络的背景下验证的方法;一个是因果方向是已知的（使用刺激的输入途径和记录场电位在其目标层的海马）和其他因果方向来自先验知识的信息流沿着经典的海马“三突触电路”。然后，在具体目标2，我们将解决的因果关系的影响和定向驱动海马theta皮层下θ发生器（SUM和MS）和测试是否格兰杰因果关系可以是一个工具，在假设驱动的调查，这个系统。我们假设，特别是，SUM参与仅限于特定的状态，因此，期望找到显着的方向驱动器从SUM到海马与快速θ在清醒的探索和阶段性发作的REM睡眠，但不是在慢θ清醒不动，和紧张性REM睡眠。另一方面，我们假设MS为来自不同来源的提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著定向驱动。 公共卫生相关性：不同频率下θ波的产生机制还不清楚，但它与行为的不同方面密切相关，这表明皮层下结构起着重要作用。本R21的目标是测试一个新提出的方法称为格兰杰因果关系的两个皮层下结构：内侧隔（MS）和乳头体上核（SUM）的有效性。

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).