Safety Learning and Plasticity in the Insular Cortex

岛叶皮质的安全学习和可塑性

• 批准号: 8720819
• 负责人: John Paul Christianson
• 金额: $ 24.9万
• 依托单位: BOSTON COLLEGE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-15 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8720819
• 关键词: Action Potentials; Amygdaloid structure; Anxiety; Behavior; Behavior Control; Behavioral Genetics; Behavioral Model; Cells; Characteristics; Colorado; Complex; Conditioned Stimulus; Corpus striatum structure; Cues; Dendrites; Deposition; Detection; Development Plans; Diagnosis; Discrimination; Dorsal; Electrodes; Environment; Equipment; Event; Exposure to; Extinction (Psychology); Extramural Activities; Failure; Fright; Funding; Future; Goals; In Vitro; Institutes; Knowledge; Laboratories; Lateral; Lead; Learning; Lesion; Measures; Medial; Mediating; Membrane Potentials; Memory; Mentors; Methods; Modeling; Neuronal Plasticity; Neurons; Neurosciences; Organism; Pathway interactions; Pilot Projects; Positioning Attribute; Post-Traumatic Stress Disorders; Postdoctoral Fellow; Potassium Channel; Prefrontal Cortex; Procedures; Process; Psychology; Psychopathology; Public Health; Rattus; Records; Research; Research Personnel; Research Project Grants; Resources; Role; Safety; Sensory; Shock; Signal Transduction; Stimulus; Stress; Structure; Symptoms; Synapses; Synaptic plasticity; System; Techniques; Testing; Thalamic structure; Time; Tracer; Training; Training Activity; Universities; Vertebral column; Work; abstracting; base; career development; conditioned fear; density; graduate student; hippocampal pyramidal neuron; inhibitor/antagonist; learning extinction; meetings; neuromechanism; novel; patch clamp; programs; psychologic; reconstruction; relating to nervous system; resilience; safety study; sensory stimulus; skills; stress resilience; stressor; trend; undergraduate student

Project Summary/Abstract Candidate: Dr. John Christianson is a F32-funded research associate with extensive knowledge the neural mechanisms underlying resilience and vulnerability to anxiety and fear behavior. Past research has identified that psychological variables, including behavioral control over stress and safety signals during stress lead to a resilience from stress-induced anxiety. Furthermore, he has identified causal roles for the medial prefrontal cortex and insular cortex, respectively, in these stress-mitigating effects. His immediate goal is to advance his academic and technical skills in order to enact an independent research program studying the neural basis of safety learning and fear inhibition by safety. The K99/R00 proposal is a key component in this pursuit. Career Development Plan: Dr. Christianson¿s proposed training activities consist of: 1) training in electrophysiological techniques for the study of neuroplasticity, 2) attendance and participation at scientific meetings in which the scientific content revolves around learning and memory, 3) mentoring and training of undergraduate and graduate students on independent research projects within the sponsors¿ laboratories. Environment: The research will be conducted in the University of Colorado¿s Psychology & Neuroscience Department and the Institute of Behavioral Genetics. Co-sponsors, Drs Steven Maier and Donald Cooper are established investigators in the fields of stress, learning & memory and neuroplasticity. Both labs have a sufficient extramural funding to support the proposed research and excellent records mentoring postdoctoral fellows. Furthermore, the laboratory space is adequate and equipment state-of-the art. Research: The proposed studies test two complementary hypotheses relating safety learning. Safety learning is a Pavlovian process by which sensory stimuli come to predict the non-occurrence of an aversive event. First: Safety learning occurs in the insular cortex. This will be tested in several ways including i) pharmacological inhibition of insular cortex at the times when a rat is learning or recalling the safety cue, ii.) in vitro whole-cell patch clamp assessment of intrinsic excitability of amygdala-projecting insular cortex neurons and iii.) multiple- electrode assessment of plasticity within insular cortex synapses. Second: Exposure to uncontrollable stress, a laboratory model of posttraumatic stress disorder (PTSD), will interfere with learning and expression of safety signals. This hypothesis will be tested by interpolating uncontrollable stress before or after the safety learning. Together these complementary approaches will lead to a significant advancement in understanding of the neural mechanisms underlying safety and provide a paradigm for studying pathological safety learning as occurs in PTSD.

项目摘要/摘要 候选人： 约翰·克里斯汀森博士是F32资助的研究助理，对神经机制有广泛的了解 潜在的对焦虑和恐惧行为的韧性和脆弱性。过去的研究已经证实 心理变量，包括对压力的行为控制和压力期间的安全信号，会导致 从压力引起的焦虑中恢复能力。此外，他还确定了内侧前额叶的因果关系。 在这些缓解压力的作用中，大脑皮层和岛叶皮质分别如此。他的近期目标是推进他的 学术和技术技能，以制定一个独立的研究计划，研究神经基础 安全学习和害怕受到安全的抑制。K99/R00提案是这一努力的关键组成部分。 职业发展计划： S博士建议的培训活动包括：1)对患者进行电生理技术培训 神经可塑性研究，2)出席和参与科学会议，其中科学内容 围绕学习和记忆，3)指导和培训本科生和研究生 赞助商实验室内的独立研究项目。 环境： 这项研究将在科罗拉多大学S心理与神经科学系进行， 行为遗传学研究所。共同赞助商史蒂文·迈尔和唐纳德·库珀成立 压力、学习记忆和神经可塑性领域的研究人员。两个实验室都有足够的 外部资金，以支持拟议的研究和优秀的记录，指导博士后研究员。 此外，实验室空间充足，设备先进。 研究： 拟议的研究测试了两个与安全学习相关的互补假设。安全学习是一种 巴甫洛夫过程，感官刺激通过它来预测厌恶事件不会发生。首先： 安全学习发生在岛叶皮质。这将通过几种方式进行测试，包括：i)药理学 当大鼠学习或回忆安全提示时，岛叶皮质的抑制，II。)体外全细胞培养 膜片钳对杏仁核投射的岛叶皮质神经元固有兴奋性的评估多个- 岛叶皮质突触可塑性的电极评估。第二：暴露在无法控制的压力下， 创伤后应激障碍(PTSD)的实验室模型，会干扰学习和表达的安全性 信号。这一假设将通过在安全学习之前或之后插入不可控应力来检验。 这些相辅相成的方法结合在一起将大大促进对 并为研究病理性安全学习提供了一个范例 发生在创伤后应激障碍中。