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

• 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
• 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

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.

非侵入性脑刺激的细胞类型和回路机制

项目成果

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

• DOI: 10.7554/elife.87169
• 发表时间: 2023-07-24
• 期刊: eLife
• 影响因子: 7.7
• 作者: Rimehaug AE;Stasik AJ;Hagen E;Billeh YN;Siegle JH;Dai K;Olsen SR;Koch C;Einevoll GT;Arkhipov A
• 通讯作者: Arkhipov A

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: 10.1101/2023.10.21.563440
• 发表时间: 2023
• 期刊: bioRxiv : the preprint server for biology
• 作者: Ito,Shinya;Piet,Alex;Bennett,Corbett;Durand,Séverine;Belski,Hannah;Garrett,Marina;Olsen,ShawnR;Arkhipov,Anton
• 通讯作者: Arkhipov,Anton