权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Safety Learning and Plasticity in the Insular Cortex

岛叶皮质的安全学习和可塑性

基本信息

批准号：
8260494
负责人：
John Paul Christianson
金额：
$ 9万
依托单位：
UNIVERSITY OF COLORADO
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-04-25 至 2013-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8260494
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 base career development conditioned fear density graduate student hippocampal pyramidal neuron inhibitor/antagonist learning extinction meetings neuromechanism novel patch clamp programs psychologic public health relevance reconstruction relating to nervous system resilience safety study sensory stimulus skills stress resilience stressor trend undergraduate student

项目摘要

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Learning the difference between danger and safety is critical to survival, yet in some psychiatric conditions this process fails. Without veridical detection of safety, someone may express fear or anxiety even when the environmental cues indicate that danger is unlikely. The proposed work tests the hypothesis that the insular cortex is a critical contributor to safety learning and that neuroplastic changes in the insular cortex underlie the storage and recall of safety memory. This work has important implications for the treatment and diagnosis of posttraumatic stress disorder and other conditions that involve heightened fear and anxiety.

描述（由申请人提供）：John Christianson博士是f32资助的研究助理，对焦虑和恐惧行为的弹性和脆弱性的神经机制有着广泛的了解。过去的研究已经确定，心理变量，包括对压力的行为控制和压力时的安全信号，会导致从压力引起的焦虑中恢复过来。此外，他还分别确定了内侧前额叶皮层和岛叶皮层在这些缓解压力的作用中的因果作用。他的近期目标是提高他的学术和技术技能，以便制定一个独立的研究计划，研究安全学习和安全恐惧抑制的神经基础。K99/R00提案是这一追求的关键组成部分。职业发展规划：Dr. Christianson建议的培训活动包括：1)神经可塑性研究的电生理技术培训，2)出席和参与科学内容围绕学习和记忆的科学会议，3)指导和培训本科生和研究生在赞助实验室进行独立研究项目。环境：该研究将在科罗拉多大学心理与神经科学系和行为遗传学研究所进行。共同发起人Steven Maier博士和Donald Cooper博士是压力、学习记忆和神经可塑性领域的知名研究者。这两个实验室都有足够的校外资金来支持拟议的研究和指导博士后的优秀记录。此外，实验室空间充足，设备先进。研究：提出的研究测试了两个有关安全学习的互补假设。安全学习是一个巴甫洛夫过程，通过感官刺激来预测不发生厌恶事件。第一：安全学习发生在岛叶皮层。这将通过几种方式进行测试，包括i)在大鼠学习或回忆安全提示时对岛皮层的药理抑制，ii)体外全细胞膜片钳评估杏仁核投射岛皮层神经元的内在兴奋性，iii)多电极评估岛皮层突触的可塑性。第二：暴露在无法控制的压力下，这是创伤后应激障碍（PTSD）的实验室模型，会干扰学习和安全信号的表达。这一假设将通过在安全学习之前或之后插入不可控压力来验证。这些互补的方法将在理解安全性的神经机制方面取得重大进展，并为研究PTSD中发生的病理性安全学习提供范例。