Cell Type and Circuit Mechanisms of Non-Invasive Brain Stimulation by Sensory Entrainment

感觉传导非侵入性脑刺激的细胞类型和电路机制

基本信息

批准号：
10275301
负责人：
ANTON ARKHIPOV
金额：
$ 257.2万
依托单位：
ALLEN INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-15 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10275301
关键词：
ATAC-seq Acoustic Stimulation Acute Animal Model Area Auditory Basic Science Biological Biological Models Brain Brain Diseases Cells Chronic Communities Complex Computer Models Coupling Data Development Electrophysiology (science)Epigenetic Process Experimental Models Free Will Frequencies Future Gene Expression Profiling Genetic Transcription Hour Individual Knowledge Label Light Link Maps Mediating Memory Microglia Modeling Modification Molecular Morphology Mus Nature Nerve Degeneration Neuroglia Neurons Optics Pathway interactions Pattern Periodicity Photic Stimulation Physiology Population Prefrontal Cortex Property Role Sensory Structure Techniques Testing Therapeutic Vasodilation area V1 area striata awake brain cell cell type cognitive function constriction epigenomics experimental study in vivo insight mouse model multimodality neural patterning noninvasive brain stimulation optogenetics predictive modeling relating to nervous system response simulation single-cell RNA sequencing tool transcriptomics vasomotion

项目摘要

Cell Type and Circuit Mechanisms of Non-Invasive Brain Stimulation by Sensory Entrainment Patterned sensory stimulation (PSS) is a non-invasive technique for manipulating brain activity and states, typically employing periodic light flicker or auditory tones presented at regular intervals. We and others have recently shown that PSS at certain frequencies (centered at 40 Hz) causes widespread neural entrainment and state changes in non-neuronal cell populations (including, e.g., effects on the activity of microglia and on vasomotion), improvements in memory and cognitive function, and clearance of markers of neurodegeneration in animal models of brain disease. These observations suggest a strong potential of PSS for non-invasive brain stimulation applications in basic science and as a therapeutic tool. To enable such applications, however, it is important to know the mechanisms mediating the complex effects of PSS on neurons and non-neuronal cells. These mechanisms are poorly understood. In this project, we systematically investigate mechanisms of PSS by dissecting how cell types and circuit properties in the brain mediate the entrainment of neural activity and modifications of the states of neuronal and non-neuronal cell populations, with the focus on the mouse cortex as a model system. The central component of this project is a systematic modeling effort, relying on our recent progress in integrating diverse structural and functional data into highly detailed, bio-realistic models of the mouse cortical circuits. These models will be applied and refined to simulate the effects of PSS at the level of a single cortical area (primary visual cortex) and the whole mouse cortex. We will also develop models of coupling from the activity of different neuron types to non-neuronal cells, providing insights into the effects of neuronal entrainment to PSS on, e.g., microglia and vasculature. These modeling efforts will go hand-in-hand with electrophysiology recordings in awake mice, accompanied by chronic and acute perturbations (using chemogenetics and optogenetics). In multiple iterative stages, modeling predictions regarding the roles of excitatory and inhibitory (e.g., PV, SST, VIP) cell types in different cortical layers on the entrainment to PSS will be tested experimentally, and models will be refined to match data. The project will also characterize transcriptomic and epigenetic responses to PSS in different cell types, which will be correlated with circuit effects revealed by simulations and perturbative experiments in vivo. The results of these studies will provide a rich description of molecular, cell type, and circuit mechanisms mediating the PSS effects, which will be crucial for future rational development of applications of this brain stimulation technique. Besides the knowledge, this project will also provide highly biologically realistic, ready- to-use computational models applicable for studies of PSS and other phenomena, which we will freely share with the community.

感觉传导非侵入性脑刺激的细胞类型和电路机制模式化感觉刺激（PSS）是一种用于操纵大脑活动和状态的非侵入性技术，通常采用周期性的灯光闪烁或定期出现的听觉音调。我们和其他人有最近表明，某些频率（以 40 Hz 为中心）的 PSS 会导致广泛的神经夹带和非神经元细胞群的状态变化（包括例如对小胶质细胞活性的影响和对血管舒缩）、改善记忆和认知功能以及清除神经变性标记物在脑疾病的动物模型中。这些观察结果表明 PSS 在非侵入性大脑方面具有强大的潜力刺激在基础科学中的应用和作为治疗工具。然而，为了实现此类应用，了解介导复杂效应的机制非常重要 PSS 对神经元和非神经元细胞的影响。人们对这些机制知之甚少。在这个项目中，我们通过剖析大脑中的细胞类型和回路特性，系统地研究 PSS 机制介导神经活动的夹带以及神经元和非神经元细胞状态的改变人群，重点关注小鼠皮层作为模型系统。该项目的核心组成部分是系统建模工作，依赖于我们最近在将不同的结构和功能数据整合到高度详细、生物逼真的小鼠皮质模型中电路。这些模型将被应用和完善，以在单个皮质水平上模拟 PSS 的效果区域（初级视觉皮层）和整个小鼠皮层。我们还将开发耦合模型不同神经元类型对非神经元细胞的活动，提供对神经元影响的见解 PSS 的夹带，例如小胶质细胞和脉管系统。这些建模工作将与清醒小鼠的电生理学记录齐头并进，并伴随慢性和急性扰动（使用化学遗传学和光遗传学）。在多个迭代阶段，建模关于不同皮质中兴奋性和抑制性（例如，PV、SST、VIP）细胞类型的作用的预测 PSS 夹带层将进行实验测试，模型将进行改进以匹配数据。这项目还将表征不同细胞类型对 PSS 的转录组和表观遗传反应，这将与体内模拟和微扰实验揭示的电路效应相关。这些研究的结果将提供对分子、细胞类型和电路机制的丰富描述介导 PSS 效应，这对于未来大脑应用的合理发展至关重要刺激技术。除了知识之外，该项目还将提供高度生物学现实的、现成的使用适用于 PSS 和其他现象研究的计算模型，我们将免费分享与社区。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Coordinated changes in a cortical circuit sculpt effects of novelty on neural dynamics.

皮质回路的协调变化塑造了新奇事物对神经动力学的影响。

DOI：
发表时间：
2023-10-23
期刊：
影响因子：
0
作者：
Ito, Shinya;Piet, Ale;Bennett, Corbett;Durand, Séverine;Belski, Hannah;Garrett, Marina;Olsen, Shawn R;Arkhipov, Anton
通讯作者：
Arkhipov, Anton

Simulations of cortical networks using spatially extended conductance-based neuronal models.

使用空间扩展的基于电导的神经元模型模拟皮质网络。

DOI：
发表时间：
2023-08
期刊：
影响因子：
0
作者：
Haufler, Darrell;Ito, Shinya;Koch, Christof;Arkhipov, Anton
通讯作者：
Arkhipov, Anton

Uncovering circuit mechanisms of current sinks and sources with biophysical simulations of primary visual cortex.

通过初级视觉皮层的生物物理模拟揭示电流吸收器和电流源的电路机制。

DOI：
发表时间：
2023-07-24
期刊：
影响因子：
7.7
作者：
Rimehaug, Atle E;Stasik, Alexander J;Hagen, Espen;Billeh, Yazan N;Siegle, Josh H;Dai, Kael;Olsen, Shawn R;Koch, Christof;Einevoll, Gaute T;Arkhipov, Anton
通讯作者：
Arkhipov, Anton

Uncovering population contributions to the extracellular potential in the mouse visual system using Laminar Population Analysis.

使用层流群体分析揭示群体对小鼠视觉系统细胞外潜力的贡献。

DOI：
发表时间：
2024-01-16
期刊：
影响因子：
0
作者：
Rimehaug, Atle E;Dale, Anders M;Arkhipov, Anton;Einevoll, Gaute T
通讯作者：
Einevoll, Gaute T

Modeling circuit mechanisms of opposing cortical responses to visual flow perturbations.

对视觉流扰动的相反皮质反应的电路机制进行建模。

DOI：
发表时间：
2024-03
期刊：
影响因子：
4.3
作者：
Galván Fraile, J;Scherr, Franz;Ramasco, José J;Arkhipov, Anton;Maass, Wolfgang;Mirasso, Claudio R
通讯作者：
Mirasso, Claudio R