Ontogeny of spinal glutamate receptors in nociception

描述（由申请人提供）： 这个指导研究科学家发展奖（K 01）申请提出了一个计划， 研究和培训，以扩大候选人的行为神经科学培训，以加强 行为调控的分子和神经方面。该计划将完成以下目标：1）加强和深化候选人在哥伦比亚大学发展心理生物学分部获得的神经药理学和神经解剖学技能; 2）与哥伦比亚大学的专业实验室合作，提供分子生物学和电生理学概念和技术的培训; 3）应用这些技能来研究幼年动物的伤害感受系统的发育。本研究的具体目的是探讨脊髓离子型NMDA和AMPA谷氨酸受体在大鼠个体发育早期急性疼痛和痛觉过敏中的作用。这将通过以下方式实现：1）使用药理学方法来确定脊髓NMDA和AMPA受体在出生后前3周内的伤害感受中的作用; 2）使用原位和免疫细胞化学来确定暴露于急性疼痛和炎症诱导的痛觉过敏对整个发育过程中脊髓NMDA和AMPA受体的影响; 3）采用电生理方法检测NMDA和AMPA受体在炎症损伤中的作用 对脊髓神经元的影响了解伤害性刺激对这些受体的影响对于开发疼痛管理技术非常重要，这些疼痛管理技术可以减少损伤期间的疼痛，并可能阻止早期损伤引起的伤害性系统的长期变化。拟议的培训计划是至关重要的候选人从博士后研究员过渡到一个独立的调查提供概念和技术技能，调查伤害性系统的发展。

DESCRIPTION (provided by applicant): This Mentored Research Scientist Development Award (K01) application proposes a program of research and training to extend the candidate's behavioral neuroscience training to strengthen molecular and neural aspects of behavioral regulation. The program will accomplish the following goals: 1) strengthen and deepen the candidate's neuropharmacological and neuroanatomical skills gained at the Division of Developmental Psychobiology of Columbia University; 2) provide training in molecular biological and electrophysiological concepts and techniques in collaboration with specialized laboratories at Columbia University; 3) apply these skills to investigate the development of nociceptive systems in the infant animal. The specific research aim of the proposed study is to investigate the role of spinal ionotropic NMDA and AMPA glutamate receptors in acute pain and hyperalgesia across early ontogeny in the rat. This will be done by: 1) using pharmacological methods to determine the role of spinal NMDA and AMPA receptors in nociception during the first 3 weeks after birth; 2) using in situ and immunocytochemistry to determine the impact of exposure to acute pain and inflammatory-induced hyperalgesia on spinal NMDA and AMPA receptors across development; 3) using electrophysiological methods to determine whether NMDA and AMPA recpetors play a role in inflammatory-induced injury on spinal neurons across development. Knowledge of the impact of exposure to nociceptive stimuli on these receptors is important in developing pain management techniques that reduce pain during injury and potentially block long-term changes in the nociceptive system caused by the early injury. The proposed training program is critical in the candidates transition from a postdoctoral fellow to an - independent investigator by providing conceptual and technical skills to investigate the development of nociceptive systems.