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Pan-neuronal functional imaging and anesthesia

全神经元功能成像和麻醉

基本信息

批准号：
9707361
负责人：
Christopher W Connor
金额：
$ 15.19万
依托单位：
BOSTON UNIVERSITY MEDICAL CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-15 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9707361
关键词：
Absence of pain sensation Amnesia Anesthesia procedures Anesthesiology Anesthetics Animals Architecture Behavior Behavioral Paradigm Biological Models Brain Brain region Caenorhabditis elegans Calcium Clinical Complex Data Defect Electroencephalography Fluorescence Functional Imaging Functional Magnetic Resonance Imaging Ganglia General Anesthesia Genetic Glare Human Image Individual Knowledge Lead Longevity Maps Measurement Measures Mediating Medicine Memory Microscopy Modernization Modification Molecular Molecular Analysis Movement Mus Muscle relaxation phase Nematoda Nervous system structure Neurons Optics Pain Patients Perception Physiological Physiology Population Postoperative Period Psyche structure Research Resolution Risk Sensory Signal Transduction Somatosensory Cortex Stimulus System Techniques Technology Testing Time Transgenic Organisms Translating Translations Unconscious State calcium indicator clinical practice experience experimental study fluorescence imaging hippocampal pyramidal neuron in vivo mouse model neuronal circuitry novel optical imaging promoter receptor response theories two-photon

项目摘要

Abstract Volatile anesthetics produce all stages of general anesthesia including unconsciousness, amnesia, analgesia and muscle relaxation. Once placed into this physiological state, the experience, memory and physical response to excruciating pain are all lost. However, we still do not understand mechanistically how this state of anesthesia is produced within neuronal systems such that complex mental activity is ablated while vestigial physiology is preserved. To date, research has proceeded along essentially two tracks: either the gross measurement of neuronal activity in entire regions of the brain using fMRI and EEG (which are fundamentally limited by resolution), or analysis at the molecular level looking for specific receptors for the volatile anesthetics (which has largely foundered). Astonishingly, patients can nevertheless be promptly retrieved from this state, and empirical clinical practice has reduced the risk of anesthesia to the extent that it is now an essential and universally accepted part of the modern practice of medicine. Fortunately, using novel fluorescent microscopy, we are now able to image neuronal activity in real-time, in vivo, and at resolutions capable of simultaneously capturing the activity of individual neurons and entire populations of complex neuronal networks. In this study, we apply this technique to C. elegans in which we are able to capture the activity of the entire nervous system, and to the mouse in which we capture regions of the somatosensory cortex. To discern the effect by which clinical anesthesia is achieved, it would make sense to begin with the creature with the simplest, most tractable neuronal architecture in which anesthesia is known to be inducible. C. elegans offers a simple well-mapped nervous system (302 neurons), well characterized behavioral paradigms and amenable genetics. Moreover C. elegans is well established as a model system in anesthesiology, and displays distinct stages of gross behavior under anesthesia similar to humans. Using GCaMP, a fluorescent indicator of intracellular calcium concentration expressed transgenically under a neuronal promoter, we can capture the activity of multiple neurons optically, non-invasively, and in parallel. Our experimental system will allow us to measure activity of the individual neurons within large-scale neuronal circuits to understand how subtle modifications in discrete neuronal dynamics lead to the gross but reversible functional defects at the level of the overall nervous system that result in analgesia and physical quiescence. Our study will define the effects of volatile anesthetics over increasing neuronal complexity from individual neurons to the entire nervous system. Current technology within mammalian systems is limited in scale to small subsections of the brain. We will begin complementary imaging experiments in the somatosensory cortex of the mouse that will initiate the translation of our findings and techniques to mammalian systems.

摘要