Safety Learning and Plasticity in the Insular Cortex

岛叶皮质的安全学习和可塑性

• 批准号: 8671411
• 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/8671411
• 关键词: Action Potentials; Amygdaloid structure; Anxiety; Behavior; Behavior Control; Behavioral Genetics; Behavioral Model; Cells; Characteristics; 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.

项目总结/摘要 候选人： 博士John Christianson是一名F32资助的研究助理，对神经机制有着广泛的了解。 对焦虑和恐惧行为的潜在弹性和脆弱性。过去的研究表明， 心理变量，包括对压力的行为控制和压力期间的安全信号， 从压力引发的焦虑中恢复过来此外，他还确定了内侧前额叶的因果作用， 皮质和岛叶皮质，分别在这些应力缓解效果。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， 安全学习和安全恐惧抑制。K99/R 00提案是实现这一目标的关键组成部分。 职业发展计划： 博士Christianson提出的培训活动包括：1）对 研究神经可塑性，2）出席和参与科学会议，其中的科学内容 围绕学习和记忆，3）指导和培训本科生和研究生， 赞助实验室内的独立研究项目。 工作环境： 这项研究将在科罗拉多大学的心理学和神经科学系进行， 行为遗传学研究所共同发起人，史蒂芬梅尔博士和唐纳德库珀成立 压力、学习记忆和神经可塑性领域的研究者。两个实验室都有足够的 校外资助，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： 拟议的研究测试两个互补的假设有关安全学习。安全学习是一种 一种巴甫洛夫过程，通过这种过程，感觉刺激可以预测一个令人厌恶的事件不会发生。第一个： 安全学习发生在岛叶皮层。这将以几种方式进行测试，包括i）药理学 在大鼠学习或回忆安全提示时抑制岛叶皮层，ii.）体外全细胞 膜片钳评估杏仁核投射岛叶皮层神经元的内在兴奋性和iii.）多重- 岛叶皮层突触内可塑性的电极评估。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.将通过在安全学习之前或之后插入不可控应力来检验该假设。 这些互补的方法将共同导致对人类行为的理解的重大进步。 神经机制潜在的安全，并提供了一个范式，研究病理安全学习， 发生在PTSD。