Ontogeny of spinal glutamate receptors in nociception

描述(由申请人提供)： 这项指导研究科学家发展奖(K01)的申请提出了一个计划 研究和培训，以延长候选人的行为神经科学训练，以加强 行为调节的分子和神经方面。该计划将实现以下目标：1)加强和深化应聘者在哥伦比亚大学发育心理生物学系获得的神经药理学和神经解剖学技能；2)与哥伦比亚大学专门实验室合作提供分子生物学和电生理学概念和技术方面的培训；3)应用这些技能研究幼年动物伤害性感受系统的发育。本研究的具体研究目的是探讨脊髓离子亲性NMDA和AMPA谷氨酸受体在大鼠急性疼痛和早期个体发育痛过敏中的作用。这将通过以下方法完成：1)使用药理学方法来确定出生后3周内脊髓NMDA和AMPA受体在伤害性感受中的作用；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)使用电生理学方法来确定NMDA和AMPA受体是否在炎症诱导的损伤中发挥作用 在发育过程中对脊髓神经元的影响。了解接触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，这种技术可以减少伤害期间的疼痛，并有可能阻止由早期伤害引起的伤害感受系统的长期变化。拟议的培训计划通过提供概念和技术技能来研究伤害性系统的发展，在候选人从博士后研究员向非独立研究员的转变过程中至关重要。

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.