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

职业：将感觉神经元可塑性与适应性损伤诱发的行为联系起来

• 批准号: 2047331
• 负责人: Robyn Crook
• 金额: $ 67.56万
• 依托单位: San Francisco State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-15 至 2026-02-28
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2047331&HistoricalAwards=false
• 关键词: CAREER; Linking; sensory; neuron; plasticity

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.

大多数动物，包括人类，一生中至少会经历一次亚致命伤害。受伤的动物可能会招致长期的代价，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，将伤害成本降至最低的长期行为变化可能是有利的，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，但控制损伤后行为变化的大脑机制却鲜为人知。这份职业提案的目标是揭示检测损伤的感觉神经元(伤害性感受器)的记忆样变化与补偿损伤的适应行为的长期增强之间的联系。一组进化出特别复杂的伤害诱导行为的动物是头足类软体动物(章鱼、鱿鱼和墨鱼)，它们依赖于可变的皮肤伪装，如果皮肤受伤，这种伪装就会严重受损。研究人员实验室之前的工作已经表明，头足类动物的行为发生了长期的变化，这种变化有助于受伤后的存活。这个项目特别关注神经系统是如何产生这些变化的，以及这些变化与包括哺乳动物和人类在内的其他动物的变化有什么相似或不同之处。该提案的更广泛影响包括对学龄前儿童的科学教育推广，对不同学生群体的研究培训，以及提高对无脊椎动物福利的知识。损伤诱导的可塑性是一系列长期行为变化的基础，从外周反射超敏到复杂的、情感有效的认知处理。PI先前已经表明，在头足类动物中，依赖于活动的伤害感受器敏化促进了对潜在威胁的高度警惕，并且这种高度警惕促进了生存。在防御行为中，驱动长期损伤诱导可塑性的神经机制仍然知之甚少，而且伤害性敏感化是否也在其他情况下促进健康保护行为完全未知。在这个职业项目中，首席研究员进行实验，以评估伤害性感受器内在兴奋性的永久性变化是否会驱动控制注意力和唤醒的高阶神经回路的可塑性。接下来，研究人员检查这些回路是否不仅调节防御性行为可塑性，而且还调节觅食、社交和生殖环境中的健康保护可塑性。最后，研究人员确定了无脊椎动物和脊椎动物之间是否有共同的可塑性分子机制来驱动不同的伤害诱导行为。这些研究涉及使用分子、遗传、生理和行为技术的组合。该项目为学龄前儿童以及在科学中代表性不足的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NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Post-injury pain and behaviour: a control theory perspective.

• DOI: 10.1038/s41583-023-00699-5
• 发表时间: 2023-06
• 期刊: Nature reviews. Neuroscience

Behavioral changes in senescent giant Pacific octopus (Enteroctopus dofleini) are associated with peripheral neural degeneration and loss of epithelial tissue

• DOI: 10.1016/j.cbpa.2022.111263
• 发表时间: 2022-07-04
• 期刊: COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY
• 影响因子: 2.3
• 作者: Holst, Meghan M.;Hauver, Camille M.;Crook, Robyn J.
• 通讯作者: Crook, Robyn J.