CAREER: Linking sensory neuron plasticity to adaptive injury-induced behavior

大多数动物，包括人类，在他们的一生中至少会经历一次亚致死伤害。受伤的动物可能会产生长期的成本，影响生存、繁殖和几乎所有其他方面的行为，而且往往会超出急性受伤后的时期。因此，减少伤害成本的长期行为改变可能是有利的，并在不同物种中广泛存在。然而，尽管它们对生存具有明显的重要性，但人们对损伤后控制行为变化的大脑机制知之甚少。这项CAREER提案的目的是揭示感知损伤的感觉神经元（伤害感受器）的记忆样变化与补偿损伤的适应性行为的持久增强之间的联系。头足类软体动物（章鱼、乌贼和墨鱼）已经进化出了特别复杂的受伤诱发行为，它们依靠多变的皮肤伪装，如果皮肤受伤，这种伪装会严重受损。研究者实验室之前的工作表明，头足类动物在受伤后的长期行为变化促进了生存。该项目特别关注神经系统如何产生这些变化，以及这些变化与其他动物（包括哺乳动物和人类）的相似或不同之处。该提案的更广泛影响包括向学龄前儿童提供科学教育，对不同学生群体进行研究培训，以及提高对无脊椎动物福利的认识。损伤诱发的可塑性是一系列长期行为改变的基础，从外周反射超敏反应到复杂的、情绪性的认知处理。PI先前已经表明，在头足类动物中，活动依赖的伤害敏感化促进了对潜在威胁的过度警惕，而这种过度警惕促进了生存。在防御行为中驱动长期损伤诱导的可塑性的神经机制仍然知之甚少，并且伤害敏化是否也促进其他环境中的健康保护行为是完全未知的。在这个CAREER项目中，首席研究员通过实验来评估伤害感受器固有兴奋性的永久性变化是否会驱动控制注意力和觉醒的高阶神经回路的可塑性。接下来，研究者将研究这些回路是否不仅调节防御行为可塑性，还调节觅食、社交和生殖环境中的健康保护可塑性。最后，研究者确定可塑性驱动各种损伤诱导行为的分子机制是否在无脊椎动物和脊椎动物中是共享的。这些研究结合了分子、遗传、生理和行为技术。该项目为学龄前儿童以及来自科学领域代表性不足群体的本科生和研究生提供培训和教育经验。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Most animals, including humans, will experience sub-lethal injury at least once in their lives. Injured animals can incur long-lasting costs that impact survival, reproduction, and almost every other aspect of behavior, and which often extend beyond the acute post-injury period. Long-lasting behavioral changes that minimize injury costs are therefore likely to be advantageous and widespread among diverse species. However, despite their obvious importance to survival, the brain mechanisms that govern changes in behavior after injury are poorly understood. The objective of this CAREER proposal is to reveal links between memory-like changes in sensory neurons that detect injury (nociceptors), and long-lasting enhancement of adaptive behaviors that compensate for injury. One group of animals that have evolved particularly complex injury-induced behaviors are cephalopod molluscs (octopus, squid, and cuttlefish), who rely on changeable skin camouflage that is heavily impaired if the skin is injured. Previous work in the investigator’s lab has shown long-lasting behavioral changes in cephalopods that promote survival after injury. This project focuses specifically on asking how these changes are produced by the nervous system, and how these changes may be similar or different from those of other animals, including mammals and humans. Broader impacts of the proposal include science education outreach to pre-K children, research training of diverse student populations, and improved knowledge of invertebrate animal welfare.Injury-induced plasticity underlies a range of long-term behavioral changes, ranging from peripheral reflex hypersensitivity to complex, emotionally-valenced cognitive processing. The PI has shown previously that in cephalopods, activity-dependent nociceptive sensitization promotes hypervigilance toward potential threats, and that this hypervigilance promotes survival. The neural mechanisms driving long-term injury-induced plasticity in defensive behaviors remain poorly understood, and whether nociceptive sensitization also promotes fitness-protecting behavior in other contexts is completely unknown. In this CAREER project, the principal investigator conducts experiments to evaluate whether permanent changes to the intrinsic excitability of nociceptors drives plasticity in higher-order neural circuits governing attention and arousal. Next, the investigator examines whether these circuits modulate not only defensive behavioral plasticity, but also fitness-protecting plasticity in foraging, social, and reproductive contexts. Finally the investigator determines if molecular mechanisms of plasticity driving diverse injury-induced behaviors are shared among invertebrates and vertebrates. The studies involve use of a combination of molecular, genetic, physiological and behavioral techniques. This project provides training and educational experiences for Pre-K children, as well as undergraduate and graduate students from groups under-represented in science.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.