Endocannabinoid Modulation of Nociceptive Synapses: Cellular Properties and Functional Role

伤害感觉指的是感知疼痛或伤害刺激的能力，对动物来说是至关重要的。年代的生存。疼痛刺激传递到大脑的方式可以由大脑自己改变。例如，身体的受损区域对随后的刺激变得更加敏感，以保护身体免受进一步的伤害。或者，轻轻摩擦身体疼痛的部位可以暂时减轻疼痛。该项目的目标是了解调节疼痛刺激传递到大脑的生理过程，重点关注内源性大麻素的作用，内源性大麻素是一种已知可以减轻疼痛的神经递质。此外，神经活动的某些模式刺激释放内源性大麻素递质的能力将被检查。本项目将包括行为实验、分子遗传程序和痛觉神经元（痛觉感受器）突触传递的电生理记录。我们预计(1)内源性大麻素递质会减少痛觉性突触信号，从而导致疼痛引起的行为减少；(2)非痛觉、触觉敏感神经元的激活会刺激内源性大麻素递质的释放，从而降低疼痛刺激的效果。这个项目中的实验对于理解神经生物学的基本过程至关重要，大脑是如何检测疼痛的，以及疼痛信号是如何被大脑内部的调节过程改变的。这一建议也为研究生和本科生在行为、分子遗传学和电生理记录技术方面提供了独特的培训机会。此外，该项目将在联邦资助的科学研究方面代表性不足的州（南达科他州）和一所为农村和/或第一代大学生提供服务的机构（南达科他州大学）进行。

Nociception refers to the ability to detect pain or injury-inducing stimuli, and is critical for an animal?s survival. How painful stimuli are transmitted to the brain can be changed by the brain itself. For example, damaged regions of a body become more sensitive to subsequent stimulation as a way to protect the body from further damage. Alternatively, gently rubbing a painful area of the body can temporarily reduce pain. The goal of this project is to understand the physiological processes that modulate the ways in which painful stimuli are transmitted to the brain, focusing on the effects of endocannabinoids, a class of neurotransmitters known to attenuate pain. In addition, the capacity for certain patterns of neural activity to stimulate the release of endocannabinoid transmitters will be examined. This project will include behavioral experiments, molecular genetic procedures and electrophysiological recordings of synaptic transmission by pain-sensing neurons (nociceptors). It is expected that (1) endocannabinoid transmitters will be found to decrease nociceptive synaptic signaling, which will lead to a decrease in pain-elicited behaviors and (2) that activation of non-pain, touch-sensitive neurons will stimulate the release of endocannabinoid transmitters resulting in a decrease in the effects of painful stimuli. The experiments in this project are critical to developing an understanding of a fundamental process in neurobiology, how the brain detects pain and how pain signaling can be altered by modulatory processes within the brain itself. This proposal also provides unique training opportunities for graduate and undergraduate students in behavioral, molecular genetics and electrophysiological recording techniques. Furthermore, this project will take place in a state (South Dakota) that is under-represented in terms of federally funded scientific research and at an institution (University of South Dakota) that serves a number of rural and/or first generation college students.