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

基本信息

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
项目类别：
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

项目摘要

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.

暴露于厌恶刺激会触发防御行为和食欲行为之间的适应性平衡，为了生存，需要快速获取、长期存储，并且必须灵活以适应修改有机体的内部和/或外部状态的详细特征。天平的形成、储存和灵活性对于理解这一基本过程如何运作至关重要帮助生物体在不断变化的环境中生存在模式生物海兔中，暴露于令人厌恶的环境中。刺激引起平衡，表现为同时增强防御反射（一种基本形式）学习（称为敏化）和抑制进食行为的这种平衡被储存。短期（几分钟到几小时）和长期（几天）的时间范围取决于厌恶的程度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：进食决策神经元 B51 的兴奋性降低与兴奋性增加共表达 PI 的实验室已经开始分析控制防御反射的感觉神经元。平衡的生化机制是由短期致敏和摄食抑制介导的。不同的调节剂，分别是离线、长期致敏的血清素 (5-HT) 和一氧化氮 (NO)。和摄食抑制共享NO的需求，尽管致敏和摄食抑制是不同的。厌恶经历后同时诱发的，多次经历后敏感化的长期储存研究发现，反复暴露于厌恶刺激的日子比抑制进食更持久，这表明随着时间的推移，可能会限制平衡的维持的约束的存在。通过结合体内和体外程序，这项 R15 AREA 资助将： 1) 确定是否共同的可塑性规则控制着进食和防御回路的变化；2）进一步描述了天平存储基础的调制系统，3) 检查天平的灵活性和约束余额的存储。研究结果将有助于从根本上理解如何平衡防守和防守之间的关系。食欲行为可能在正常的神经系统中产生并储存。最终为那些由正确的缺陷引起的神经系统疾病提供了重要的见解这种平衡的形成、存储和灵活性，从而与国家研究所的使命保持一致神经系统疾病和中风。拟议的实验将主要由本科生进行。学生，在 PI、研究员和/或高级研究生的监督下该项目。为德克萨斯农工大学科珀斯克里斯蒂分校这一西班牙裔服务机构提供了一个独特的机会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，该机构在该机构的代表性不足。