Mechanisms of Trace Fear Conditioning in the Developing Rat

发育中大鼠的微量恐惧调节机制

• 批准号: 8291269
• 负责人: PAMELA S HUNT
• 金额: $ 18.95万
• 依托单位: UNIVERSITY OF DELAWARE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8291269
• 关键词: Accounting; Address; Adolescent; Adult; Affect; Age; Alcohols; Amygdaloid structure; Animal Experimentation; Animals; Applications Grants; Area; Behavior; Behavioral; Biological Assay; Brain; Cognitive; Collaborations; Delaware; Development; Dorsal; Efferent Pathways; Exploratory/Developmental Grant; FOS gene; Failure; Fetal Alcohol Spectrum Disorder; Fright; Future; Gene Expression; Growth; Hippocampus (Brain); Human; Immediate-Early Genes; Infusion procedures; Intervention; Laboratories; Learning; Literature; Measures; Mediating; Memory; Molecular; N-Methyl-D-Aspartate Receptors; NMDA receptor antagonist; Neurobiology; Neuronal Plasticity; Nutritional; Outcome; Outcome Measure; Performance; Pharmaceutical Preparations; Process; Proteinase 3; Public Health; Rattus; Research; Research Personnel; Risk; Rodent Model; Role; Savings; Staging; System; Testing; Time; Training; Universities; Visual; Weaning; Work; alcohol exposure; base; brain behavior; brain tissue; clinical practice; cognitive function; college; conditioned fear; conditioning; design; developmental disease; developmental neurobiology; improved; innovation; insight; interdisciplinary approach; interest; neglect; neurobehavioral disorder; neurobiological mechanism; neurodevelopment; neuromechanism; novel; novel strategies; postnatal; prevent; relating to nervous system; research study; response; visual stimulus

DESCRIPTION (provided by applicant): This R21 exploratory grant application will study a largely neglected and poorly understood principle of the ontogeny of learning---acquisition vs. expression---that will likely yield new insights into the development and neural basis of hippocampus-dependent memory. Research on acquisition vs. expression of delay fear conditioning during ontogeny has yielded novel and unanticipated insights concerning how the amygdala and specific efferent pathways cooperate to generate learned fear. However, other developmental research with other types of learning indicates that acquisition occurs first and expression of this learning emerges later in development. To explore these two possibilities in the case of hippocampus-dependent learning, Drs. Mark Stanton and Jeff Rosen at the University of Delaware; and Dr. Pam Hunt at the College of William and Mary will use behavioral, molecular and neuropharmacological approaches to study acquisition vs. expression of trace fear conditioning in developing rats. In Aim 1, two studies in the Hunt laboratory will explore the role of acquisition vs. expression of learning in the ontogenetic emergence trace conditioning between postnatal day (PD) 23 and PD28 in the rat. In Aim 2, immediate-early-gene expression assays will be performed in the Rosen laboratory on the brains of rats tested behaviorally in Aim 1 to explore the role of developmental differences in neural activity and/or plasticity in hippocampus and amygdala in the ontogeny of trace fear conditioning. In Aim 3, two experiments in the Stanton laboratory will determine the contribution of NMDA- receptor-mediated neural plasticity in dorsal hippocampus to the ontogeny of acquisition vs. expression of visual trace conditioning in PD23-28 rats. This project is innovative because it will be the first to examine acquisition vs. expression of hippocampus-dependent learning during ontogeny using an integrated, multidisciplinary approach. If successful, it will yield novel and important insights that would be pursued more thoroughly in subsequent R01 applications. The project is also significant because it will advance the study of developmental disorders involving aberrant maturation of the hippocampus. For example, Dr. Hunt's laboratory has shown that trace fear conditioning is an especially sensitive outcome measure for studying adverse cognitive effects of developmental alcohol exposure. However, understanding of the neural mechanisms of these effects is hampered by a lack of information on brain-behavior relationships mediating trace conditioning during this period of development. This R21 project seeks to fill that gap. Finally, this project will establish a new multi-investigator collaboration that has strong potential to advance these and other important issues in the developmental neurobiology of learning.

描述（由申请人提供）：此R21探索性赠款应用程序将研究一个在很大程度上被忽视的学习原则，即学习的本体 - 收购与表达 - - 可能会产生有关海马依赖性记忆的发展和神经基础的新见解。关于习得与表达延迟恐惧调节期间的研究，对杏仁核和特定的传出途径如何配合产生了学识渊博的恐惧，从而产生了新颖和意外的见解。但是，与其他类型的学习的其他发展研究表明，获取是首先发生的，并且该学习的表达在后来出现。在海马依赖性学习的情况下，探索这两种可能性。特拉华大学的马克·斯坦顿（Mark Stanton）和杰夫·罗森（Jeff Rosen）；威廉和玛丽学院的帕姆·亨特（Pam Hunt）博士将使用行为，分子和神经药理学方法来研究习得与发育中大鼠的痕量恐惧调节的表达。在AIM 1中，亨特实验室中的两项研究将探讨习得与学习表达的作用，在发生后日（PD）23和PD28之间的学习中痕量痕量条件中的作用。在AIM 2中，将在Rosen实验室中对AIM 1的大鼠大脑进行即时 - 本获得的表达测定法，以探讨在海马和杏仁核中神经活动和/或可塑性在痕量恐惧条件的个体基础中的作用。在AIM 3中，斯坦顿实验室中的两个实验将确定背部海马中NMDA受体介导的神经可塑性对pd23-28大鼠的视觉痕量调节的表达的贡献。该项目具有创新性，因为它将是第一个使用综合的多学科方法在本体发育过程中检查采集与海马依赖性学习的表达的人。如果成功，它将产生新颖而重要的见解，这些见解将在随后的R01应用中更彻底地追求。该项目也很重要，因为它将进步研究涉及海马异常成熟的发育障碍。例如，亨特（Hunt）博士的实验室表明，痕量恐惧调节是研究发展性酒精暴露的不良认知影响的特别敏感结果。然而，缺乏有关在这一发展期间介导痕量调节的脑行为关系的信息，从而阻碍了对这些作用神经机制的理解。这个R21项目旨在填补这一空白。最后，该项目将建立一个新的多侵袭者合作，该协作具有强大的潜力，可以推进学习神经生物学中的这些和其他重要问题。