Remote Modulation of the Peripheral Nervous System

周围神经系统的远程调节

• 批准号: 10002786
• 负责人: Sarah Amy Stanley
• 金额: $ 13万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-24 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10002786
• 关键词: Afferent Neurons; Animals; Area; Biological; Biomedical Engineering; Calcium; Cations; Cells; Characteristics; Chimeric Proteins; Chlorides; Diabetes Mellitus; Disease; Electromagnetic Fields; Electromagnetics; Electrophysiology (science); Enterobacteria phage P1 Cre recombinase; Excision; FOS gene; Ferritin; Gene Delivery; Genes; Image; Immunohistochemistry; Implant; Internal Ribosome Entry Site; Ion Channel; Ions; Islets of Langerhans; Kinetics; Ligands; Light; Magnetism; Malignant Neoplasms; Methods; Modification; Motion; Mus; Nerve; Neural Inhibition; Neural Pathways; Neurons; Obesity; Optical Methods; Organ; Pancreas; Pancreatic Hormones; Peripheral; Peripheral Nerves; Peripheral Nervous System; Physiological; Population; Proteins; Regulation; Role; Route; Sensory; Signal Transduction; Structure; System; TRPV1 gene; Technology; Temperature; Testing; Time; Tissues; Translations; Vanilloid; Viral; Viral Vector; Virus; cell type; clinical application; glucose tolerance; in vivo; iron oxide nanoparticle; magnetic field; nanoparticle; nerve supply; neuroregulation; neurotransmission; novel; novel therapeutic intervention; promoter; radio frequency; receptor; relating to nervous system; response; tool

Project Summary Modulating the activity of peripheral nerves innervating specific organs and defined cell types within these organs will help us understand the relationship between neural signals and organ function. We propose to develop and validate the use of non-invasive neural modulation in the peripheral nervous system in vivo. Many tools can be used for temporal regulation of neural activity in the CNS, from light activated channels to designer receptors but these are not universally applicable, particularly in the periphery. Optical methods require permanent implants which may be difficult to fix or even cause damage in peripheral tissues. In addition, these tools only activate local neural populations in a small portion of an organ. In contrast, designer receptors and their ligands can target neurons across a larger area but have a relatively slow time course. Neural modulation with radiowaves or magnetic fields allows remote, rapid activation or inhibition of neural activity across an entire organ. We have recently shown that a distinctive combination of non-invasive radiowave and magnetic field signals, biological ferritin nanoparticles and bioengineered ion channels can be used to remotely activate and inhibit CNS neural activity in freely moving animals. Targeted neurons express genetically encoded nanoparticles tethered to a modified ion channel, transient receptor potential vanilloid 1, TRPV1. Radiowaves or magnetic fields freely penetrate tissue to heat and/or move the nanoparticle and activate TRPV1. Modifications of TRPV1 allow either neural activation or silencing. We will now develop and validate tools for non-invasive activation and silencing of peripheral nerves using viral vectors applicable to several species and we will demonstrate their utility by modulating innervation of the endocrine pancreas. Specifically, we will develop, validate and characterize 1) tools for remote activation and inhibition of neurons innervating the pancreas using viruses with retrograde spread and neuron-specific expression of activating or inhibitory constructs and 2) tools for remote activation and inhibition of specific neural pathways (parasympathetic, sympathetic and sensory) innervating the pancreas. We will develop a range of tools for remote modulation of parasympathetic, sympathetic and sensory peripheral nerves innervating an organ. These tools will be broadly applicable and extend the methods available to investigate the physiological roles of peripheral nerves in regulating organ function.

项目总结

项目成果

Mapping and specific viral targeting of peripheral pancreatic innervation.

周围胰腺神经支配的绘图和特异性病毒靶向。

• 发表时间: 2022
• 期刊: FASEB journal : official publication of the Federation of American Societies for Experimental Biology
• 作者: JimenezGonzalez,Maria;Li,Rosemary;Pomeranz,LisaE;Alvarsson,Alexandra;Marongiu,Roberta;Hampton,RollieF;Vasavada,RupangiC;Schwartz,GaryJ;Stanley,SarahA
• 通讯作者: Stanley,SarahA

Optical Clearing and 3D Analysis Optimized for Mouse and Human Pancreata.

• DOI: 10.21769/bioprotoc.4103
• 发表时间: 2021-08
• 期刊: Bio-protocol
• 影响因子: 0.8
• 作者: A. Alvarsson;M. Jimenez-Gonzalez;Rosemary Li;Carolina Rosselot;N. Tzavaras;Zhuhao Wu;S. Stanley

Uncovering a possible role of reactive oxygen species in magnetogenetics

• DOI: 10.1038/s41598-020-70067-1
• 发表时间: 2020-08-04
• 期刊: SCIENTIFIC REPORTS
• 影响因子: 4.6
• 作者: Brier, Matthew, I;Mundell, Jordan W.;Dordick, Jonathan S.
• 通讯作者: Dordick, Jonathan S.