Collaborative Research: Mechanisms and Functions of Nociceptive Sensitization in Dissimilar Molluscs

所有动物，包括人类，都会经历伤害，每一个被检查的物种都表现出适应性反应，以帮助避免受伤或再次受伤。对人类的伤害会导致疼痛，这种疼痛可能是长期的(甚至是永久性的)，有时是无法治愈的。虽然已经通过对更简单的动物(包括选定的无脊椎动物)进行比较研究，了解了人类生物学的其他方面，但关于无脊椎动物对伤害的行为和神经反应的系统比较研究一直缺乏。这个项目将比较两种无脊椎动物对周围损伤的行为和神经反应。由于它们巨大的神经元，这两种无脊椎动物一直是神经科学的开创性发现的来源：普通的大西洋鱿鱼Lolio和一种大型海洋蜗牛Aplysia。两者都是软体动物，但它们的生活方式和认知能力截然不同。有待检验的假说包括：(1)在两个物种的外周感觉神经元中，损伤诱导的持久行为敏化涉及类似于已报道的哺乳动物效果的类似的长期反应性增强，(2)这些变化是由共同的化学信号诱导的，这些化学信号也导致哺乳动物的炎性疼痛，(3)大脑鱿鱼而不是小脑蜗牛表现出对伤害的持续意识，(4)鱿鱼防御反应的敏化通过降低对捕食性攻击的脆弱性而增加了在受伤状态下存活的机会。这项研究项目的更广泛的影响将是鼓励使用软体动物来探索涉及核心机制的基本行为模式的进化，这些核心机制是广泛保守的，可能对人类疼痛来说是重要的，以及对未来科学家(包括本科生)的教育，他们对行为神经生物学的比较和进化方法感兴趣。由此产生的科学信息将发表在科学期刊上并传播，以促进在研究中合理和人道地对待软体动物和其他无脊椎动物。

All animals, including humans, experience injury, and every species examined shows adaptive responses to help avoid injury or re-injury. Injury to humans causes pain, which can be long lasting (even permanent) and sometimes untreatable. Although much has been learned about other aspects of human biology through comparative studies of simpler animals, including selected invertebrates, systematic comparative studies of behavioral and neural responses to injury in invertebrates have been lacking. This project will compare behavioral and neural responses to peripheral injury in two invertebrates that, because of their giant neurons, have been sources of pioneering discoveries in neuroscience: the common Atlantic squid, Loligo, and a large marine snail, Aplysia. Both are molluscs, but they have very different life styles and cognitive capabilities. Hypotheses to be tested include: (1) In the peripheral sensory neurons of both species, injury-induced, long-lasting behavioral sensitization involves a similar long-term enhancement of responsiveness that resembles the effects reported in mammals, (2) these changes are induced by common chemical signals that also drive inflammatory pain in mammals, (3) the large-brained squid, but not small-brained snail display ongoing awareness of an injury, and (4) sensitization of defensive responses in the squid increases the chances of survival in a wounded state by decreasing the vulnerability to predatory attacks. The broader impacts of this research project will be the encouragement of the use of molluscs to explore the evolution of fundamental behavioral patterns involving core mechanisms that are widely conserved and may be important for human pain, and the education of future scientists (including undergraduates) interested in comparative and evolutionary approaches to behavioral neurobiology. The resulting scientific information will be published in scientific journals and disseminated to foster rational and humane treatment of molluscs and other invertebrates in research.