Collaborative Research: Dynamic interactions of individual neurons in supporting hippocampal network oscillations during behavior

合作研究：行为过程中单个神经元的动态相互作用支持海马网络振荡

基本信息

批准号：
2002863
负责人：
Horacio Rotstein
金额：
$ 62.5万
依托单位：
New Jersey Institute of Technology
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2020
资助国家：
美国
起止时间：
2020-10-01 至 2025-09-30
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2002863&HistoricalAwards=false
关键词：
Collaborative Research Dynamic interactions individual

项目摘要

Cognitive and motor behavior in the brain is controlled by networks of highly interconnected neurons. Neurons communicate via signals called spikes, which are generated by complex biological mechanisms. These mechanisms crucially depend on the subthreshold membrane potential activity, which is controlled by the complex interaction of ionic currents among other factors. Although the spiking patterns of the individual neurons are typically not regular, certain neuronal networks produce periodic oscillatory patterns. Important among them is the theta rhythm (4-10 Hz), which has been recorded in various brain areas by global activity measures, such as electroencephalography (EEG) or extracellular local field potentials (LFPs). Theta oscillations have been observed during motor activity and REM sleep, and are thought to play important roles in navigation, episodic memory and learning. Theta oscillations have also been observed at the subthreshold membrane potential level in brain slice preparations, and in behaving animals in the hippocampal CA1 area. However, how the oscillatory activity at the network level is linked to the biophysical properties of individual neurons remains largely unknown. In this project, the investigators will address this question using a combined experimental/theoretical approach. The Boston University team will perform experiments in behaving animals in CA1, and the NJIT team will carry out detailed computational modeling. This research is expected to generate a framework for describing and understanding how high-level neuronal oscillations depend on the oscillatory activity of individual neurons through complex network interactions. The PIs will also work to disseminate their imaging technology to the scientific community. This project will contribute to the cross-disciplinary training of students and postdoctoral trainees in both experimental and computational neuroscience. The central hypothesis of this project is that theta oscillations in the hippocampus are generated by resonant mechanisms involving the intrinsic properties of individual neurons, and circuit interactions that are tuned to amplify theta frequency inputs from the medial septum and possibly other external sources. We will address this hypothesis from an interdisciplinary perspective involving in vivo experiments, computational modeling, and dynamical systems analysis. We aim to understand the cellular and circuit mechanisms of hippocampal theta oscillations in vivo, and to create a theoretical framework to describe the biophysical and dynamic links between the oscillatory properties of individual neurons and network oscillations. The Boston University team will deploy a novel voltage imaging technique to measure subthreshold voltage dynamics and spiking activity from individual hippocampal neurons of defined cell types, including pyramidal cells and local interneurons (e.g. parvalbumim (PV)- and somatostatin (SOM)- positive ones) during behavioral states with varying levels of LFP theta oscillations. Additionally, to test the causal role of these interneurons in supporting theta oscillations, precision optogenetic activation and silencing will be used. The NJIT team will build biophysical models of the hippocampal network that include the intrinsic subthreshold oscillatory properties of the participating neurons and inputs from other areas (e.g., medial septum) to produce theta LFP oscillations. The results of the proposed research will provide mechanistic insights on the formation of hippocampal CA1 network oscillations with implications to learning, memory and other cognitive functions.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

大脑中的认知和运动行为由高度相互连接的神经元网络控制。神经元通过称为尖峰的信号通信，这些信号是由复杂的生物学机制产生的。这些机制至关重要地取决于亚阈值膜的潜在活性，这是由离子电流的复杂相互作用控制的。尽管单个神经元的尖峰模式通常不定期，但某些神经元网络会产生周期性的振荡模式。其中重要的是theta节奏（4-10 Hz），该节奏已通过全球活动措施在各种大脑区域记录，例如脑电图（EEG）或细胞外局部田间电位（LFPS）。在运动活动和REM睡眠期间，已经观察到Theta振荡，并被认为在导航，情节记忆和学习中起着重要作用。在脑切片制剂中的亚阈值膜电位水平以及海马CA1区域的行为动物中，还观察到theta振荡。但是，网络水平上的振荡活性与单个神经元的生物物理特性有关，在很大程度上未知。在这个项目中，研究人员将使用合并的实验/理论方法来解决这个问题。波士顿大学团队将在CA1中进行行为动物的实验，NJIT团队将进行详细的计算建模。预计这项研究将产生一个框架，以描述和了解高级神经元振荡如何通过复杂的网络相互作用来依赖单个神经元的振荡活性。 PI还将致力于将其成像技术传播给科学界。该项目将有助于实验和计算神经科学的学生和博士后学员的跨学科培训。该项目的中心假设是，海马中的theta振荡是由涉及单个神经元的固有特性的谐振机制产生的，并且经过调整以扩大内侧spepun的theta频率输入的电路相互作用。我们将从涉及体内实验，计算建模和动态系统分析的跨学科角度来解决这一假设。我们旨在了解体内海马theta振荡的细胞和电路机制，并创建一个理论框架，以描述单个神经元和网络振荡的振荡特性之间的生物物理和动态联系。波士顿大学团队将部署一种新型的电压成像技术，以测量定义细胞类型的单个海马神经元的亚阈值电压动态和尖峰活动，包括金字塔细胞和局部神经元（例如，parvalbumim（pv） - parvalbumim（pv） - 和somatostatin（somatostatin（som） - 阳性（som） - 阳性级别的lffp thet lff。此外，为了测试这些神经元在支撑theta振荡中的因果作用，将使用精确的光遗传激活和沉默。 NJIT团队将建立海马网络的生物物理模型，其中包括参与神经元的固有子阈值振荡特性和来自其他区域（例如内侧隔膜）的投入，以产生Theta LFP振荡。拟议研究的结果将提供有关在学习，记忆和其他认知功能影响的海马CA1网络振荡的机械见解。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛影响的审查标准来通过评估来支持的。