Characterization of the adaptive balance between defensive and appetitive behaviors induced by aversive experience

厌恶体验引起的防御行为和食欲行为之间的适应性平衡的表征

• 批准号: 10046921
• 负责人: Riccardo Mozzachiodi
• 金额: $ 33.81万
• 依托单位: TEXAS A&M UNIVERSITY-CORPUS CHRISTI
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-18 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10046921
• 关键词: Afferent Neurons; Animal Model; Animals; Aplysia; Appetitive Behavior; Aversive Stimulus; Back; Behavior; Behavioral; Biochemical; Biomedical Research; Brain; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Decision Making; Desire for food; Environment; Equilibrium; Exposure to; Feeding behaviors; Goals; Grant; Hispanic-serving Institution; Hour; Impairment; In Vitro; Institution; Knowledge; Lead; Learning; Maintenance; Measures; Mediating; Mission; Modification; National Institute of Neurological Disorders and Stroke; Nature; Nervous system structure; Neurons; Neurosciences; Nitric Oxide; Organism; Outcome; Output; Pathway interactions; Pattern; Postdoctoral Fellow; Procedures; Process; Protocols documentation; Reflex action; Reporting; Research; Role; Serotonin; Signal Transduction; Site; South Texas; Stimulus; Supervision; Synapses; System; Texas; Time; Training; Universities; experience; experimental study; feeding; flexibility; graduate student; in vivo; insight; nervous system disorder; neural circuit; novel; undergraduate student

Exposure to aversive stimuli triggers an adaptive balance between defensive and appetitive behaviors, which, for survival, needs to be acquired rapidly, stored over time, and must be flexible to accommodate modifications in the organism’s internal and/or external state. A detailed characterization of the mechanisms underlying the formation, storage and flexibility of the balance is critical to understand how this fundamental process operates to help organisms survive in a changing environment. In the model organism Aplysia, exposure to aversive stimuli induces a balance that manifests as concurrent enhancement of defensive reflexes (an elementary form of learning known as sensitization) and suppression of the appetitive behavior of feeding. This balance is stored in short-term (minutes to hours) and long-term (days) timeframes depending on the amount of aversive exposure. The balance is sustained, at least in part, by changes at key sites within the corresponding neural circuits: decreased excitability of feeding decision-making neuron B51 co-expressed with increased excitability of the sensory neurons controlling defensive reflexes. The PI’s lab has begun to analyze the cellular and biochemical mechanism of the balance. Short-term sensitization and feeding suppression are mediated by distinct modulators, serotonin (5-HT) and nitric oxide (NO), respectively. Conversely, long-term sensitization and feeding suppression share the requirement of NO. Although sensitization and feeding suppression are concurrently induced following aversive experience, the long-term storage of sensitization following multiple days of repeated exposures to aversive stimuli has been found to outlast the suppression of feeding, suggesting the presence of constraints that may limit the maintenance of the balance over time. Using a combination of in vivo and in vitro procedures, this R15 AREA grant will: 1) determine whether common plasticity rules govern changes in feeding and defensive circuits; 2) further characterize the modulatory systems underlying the storage of the balance and 3) examine flexibility and constraints in the storage of the balance. The outcomes will contribute to the fundamental understanding of how the balance between defensive and appetitive behaviors in generated and stored in the normal nervous system. The acquired knowledge may ultimately provide important insights into those neurological disorders caused by deficits in the correct formation, storage and flexibility of this balance, thus aligning with the mission of the National Institute of Neurological Disorders & Stroke. The proposed experiments will be performed primarily by undergraduate students, under the supervision of the PI, research associate and/or a senior graduate student(s). This project represents a unique opportunity for Texas A&M University – Corpus Christi, a Hispanic-Serving Institution, to increase its visibility in biomedical research, and for its undergraduate students to conduct research in the field of neuroscience, which is underrepresented at this institution.

暴露在令人厌恶的刺激下会触发防御和食欲行为之间的适应性平衡， 为了生存，需要快速获得，随着时间的推移存储，并且必须灵活地适应修改 在生物体的内部和/或外部状态下。对潜在的机制的详细描述 平衡的形成、存储和灵活性是理解这一基本过程如何运作的关键 以帮助有机体在不断变化的环境中生存。在模式生物海兔中，暴露在令人厌恶的 刺激诱导一种平衡，表现为同时增强防御反射(初级形式 学习的敏感化)和抑制食欲行为。该余额将被存储 以短期(几分钟到几小时)和长期(几天)的时间框架表示，具体取决于厌恶的数量 曝光。这种平衡至少部分是通过相应神经内关键部位的变化来维持的 回路：喂养决策神经元B51兴奋性降低与兴奋性增加共表达 控制防御反射的感觉神经元。私家侦探的实验室已经开始分析细胞和 平衡的生化机制。短期敏化和取食抑制是由 不同的调节剂，分别是5-羟色胺(5-羟色胺)和一氧化氮(NO)。相反，长期的敏感化 取食抑制与NO的要求相同。虽然敏化和取食抑制 同时诱导后的厌恶体验，长期储存的敏感化后多次 研究发现，反复暴露在令人厌恶的刺激下的时间比抑制进食的时间更长，这表明 限制因素的存在可能会限制随着时间的推移保持平衡。 使用体内和体外程序的组合，这项R15区域拨款将：1)决定是否 共同的可塑性规则支配着馈电和防御电路的变化；2)进一步表征了 基础的调节系统的余额和3)检查灵活性和限制在 余额的存储。 这些结果将有助于从根本上理解防御性和开放性之间的平衡 食欲行为产生并储存在正常的神经系统中。所获得的知识可以 最终为正确的大脑功能缺陷引起的神经功能障碍提供重要的见解 这一平衡的形成、储存和灵活性，从而与国家科学研究所的使命相一致 神经性疾病和中风。拟议的实验将主要由本科生进行。 学生，在PI的指导下，研究助理和/或一名高级研究生(S)。这个项目 对于德克萨斯A&M大学来说，这是一个独特的机会-科珀斯·克里斯蒂，一家为拉美裔服务的机构 提高其在生物医学研究中的知名度，并让其本科生在该领域进行研究 神经科学的研究，这在这个机构中的代表性不足。