Spencer Nick J, Hibberd Tim J, Lagerström Malin, Otsuka Yoichiro, Kelley Nigel
College of Medicine and Public Health, Centre for Neuroscience, Flinders University, Bedford Park, Australia.
College of Medicine and Public Health, Centre for Neuroscience, Flinders University, Bedford Park, Australia.
Brain Res. 2018 Aug 15;1693(Pt B):159-164. doi: 10.1016/j.brainres.2018.02.002. Epub 2018 Feb 7.
Painful stimuli arising within visceral organs are detected by peripheral nerve endings of spinal afferents, whose cell bodies are located in dorsal root ganglia (DRG). Recent technical advances have made it possible to reliably expose and inject single DRG with neuronal tracers or viruses in vivo. This has facilitated, for the first time, unequivocal identification of different types of spinal afferent endings in visceral organs. These technical advances paved the way for a very exciting series of in vivo experiments where individual DRG are injected to facilitate opsin expression (e.g. Archaerhodopsin). Organ-specific expression of opsins in sensory neurons may be achieved by retrograde viral transduction. This means activity of target-specific populations of sensory neurons, within single DRG, can be modulated by optogenetic photo-stimulation. Using this approach we implanted micro light-emitting diodes (micro-LEDs) adjacent to DRG of interest, thereby allowing focal DRG-specific control of visceral and/or somatic afferents in conscious mice. This is vastly different from broad photo-illumination of peripheral nerve endings, which are dispersed over much larger surface areas across an entire visceral organ; and embedded deep within multiple anatomical layers. Focal DRG photo-stimulation also avoids the potential that wide-field illumination of the periphery could inadvertently activate other closely apposed organs, or co-activate different classes of axons in the same organ (e.g. enteric and spinal afferent endings in the gut). It is now possible to selectively control nociceptive and/or non-nociceptive pathways to specific visceral organs in vivo, using wireless optogenetics and micro-LEDs implanted adjacent to DRG, for targeted photo-stimulation.
内脏器官内产生的疼痛刺激由脊髓传入神经的外周神经末梢检测，其细胞体位于背根神经节（DRG）。最近的技术进步使得在体内可靠地暴露单个DRG并注射神经元示踪剂或病毒成为可能。这首次促进了对内脏器官中不同类型脊髓传入末梢的明确识别。这些技术进步为一系列非常令人兴奋的体内实验铺平了道路，在这些实验中，单个DRG被注射以促进视蛋白表达（例如古紫质）。视蛋白在感觉神经元中的器官特异性表达可通过逆行病毒转导实现。这意味着单个DRG内目标特异性感觉神经元群体的活动可通过光遗传学光刺激进行调节。使用这种方法，我们在感兴趣的DRG附近植入了微型发光二极管（微型LED），从而在清醒小鼠中实现对内脏和/或躯体传入神经的局部DRG特异性控制。这与外周神经末梢的广泛光照射有很大不同，外周神经末梢分散在整个内脏器官的更大表面积上，并深埋在多个解剖层中。局部DRG光刺激还避免了外周的广域照射可能无意中激活其他紧密相邻器官或共同激活同一器官中不同类别的轴突（例如肠道中的肠传入和脊髓传入末梢）的可能性。现在可以使用无线光遗传学和植入DRG附近的微型LED在体内选择性地控制通往特定内脏器官的伤害性和/或非伤害性通路，以进行靶向光刺激。
