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Spatiotemporal Coding in the Pain Circuit Along the Spine-brain Continuum

沿着脊柱-大脑连续体的疼痛回路的时空编码

基本信息

批准号：
10205394
负责人：
David Allenson Borton
金额：
$ 8.96万
依托单位：
CLEVELAND CLINIC LERNER COM-CWRU
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：
2021-02-01 至 2022-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10205394
关键词：
Acute Pain Afferent Neurons Animals BRAIN initiative Behavior Behavioral Brain Calcium Cations Cells Cellular biology Chronic Code Data Detection Electrophysiology (science)Experimental Designs Family Fiber Future Goals Grant Head Health Sciences Image Implant In Vitro Interneurons Intervention Investigation Light Medical Medicine Methodology Methods Microelectrodes Microscope Microscopy Modeling Monitor Mus Nerve Fibers Neuraxis Neurons Neurosciences Nociception Optics Outcome Pain Pain intensity Parents Parvalbumins Perception Peripheral Physicians Posterior Horn Cells Process Reflex action Reporting Research Rest Scientist Sensory Signal Transduction Site Spinal Spinal Cord Spinal cord posterior horn TRPV1 gene Tactile Techniques Thalamic structure Time Touch sensation Training Transgenic Mice Underrepresented Populations Universities Vertebral column Video Recording Viral Work afferent nerve awake base calmodulin-dependent protein kinase II career cell type chronic pain detection assay dorsal horn excitatory neuron experience extracellular improved in vivo medical schools member millisecond neurophysiology optogenetics pain processing pain signal receptor relating to nervous system response skills spatiotemporal transmission process

项目摘要

PROJECT SUMMARY Understanding the cellular biology and neurophysiology of sensory processing in the spinal cord is fundamental to advancing medical intervention in the treatment of chronic and acute pain conditions. The current understanding of the neurophysiology of spinal cord circuitry is founded on experimental single-unit electrophysiology on anesthetized animals and in-vitro studies, but limited data exist from in-vivo functional circuitry of sensory signals. Part of the challenge to such experimentation has been the limited capacity for monitoring electrophysiologic signals in awake animals and inducing reliable activation of pain fibers. Consequently, the activity of specific neuronal subtypes in propagating excitatory and inhibitory signals involved in the transmission of pain signals remains unknown in-vivo. Recently, we have developed a pain detection assay consisting of a lick behavior in response to optogenetic activation of predominantly nociceptive peripheral afferent nerve fibers in head-restrained transgenic mice expressing Channelrhodopsin 2 (ChR2) in transient receptor potential cation channel subfamily V member 1 (TRPV1) containing neurons. In this model, mice are trained to provide lick reports to the detection of light-evoked nociceptive stimulation to the hind paw. Our nociceptive lick-report detection assay enables a host of investigations into the millisecond, single-cell, neural dynamics underlying pain processing in the central nervous system of awake behaving animals. Further, we have developed a “backpack drive” to provide multi-site chronic extracellular recordings from dorsal horn neurons derived from superficial laminas II-III. Unfortunately, such electrophysiology cannot be used to determine cellular subclasses during recording. Here, we will focus on advancing our ability to record cell-type-specific activity in the dorsal horn in response to light-activated TRPV1 containing neurons in the periphery. We will develop a reliable method for achieving consistent GCaMP6-family expression in specific neuronal cell types (e.g. CaMKII, PV) involved in the specific activation of pain signals through our optogenetic stimulation experimental design. We will optimize a spinal optical window to perform awake Calcium imaging during time-locked tactile input and characterize calcium dynamics in neuronal subtypes in the dorsal horn during behavioral tasks. This work will establish a methodology to collect temporal dynamics of large classes of neurons in the dorsal horn in response to time-locked, spatially-precise, and amplitude-modulated input in the periphery leading to improved understanding of acute pain conditions.

项目总结