Cholinergic modulation of excitatory synapse formation

兴奋性突触形成的胆碱能调节

• 批准号: 6946299
• 负责人: ROBERT B LEVY
• 金额: $ 5.35万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6946299
• 关键词: AMPA receptors; NMDA receptors; acetylcholine; cholinergic receptors; developmental neurobiology; early experience; electrophysiology; excitatory aminoacid; glutamate receptor; immunocytochemistry; laboratory rat; somesthetic sensory cortex; synapses; synaptogenesis

DESCRIPTION (provided by applicant): Sensory experience early in life leads to the establishment and refinement of synaptic connections, through cellular mechanisms that are not yet understood. Electron microscopic immunocytochemical (EM-ICC) studies have provided information about the molecular composition of developing cortical synapses. However, it has been difficult to correlate this information with the results of electrophysiological studies. The proposed research uses a novel combination of electrophysiology, tract-tracing and EM-ICC to examine the molecular composition of physiologically/anatomically characterized synapses in somatosensory cortex. In particular, recent evidence suggests that the activity of central nicotinic acetylcholine receptors is important for the early development of excitatory cortical synapses. The presence of these receptors will be assessed in synapses between identified cortical neurons where the maturity of the connection has been determined physiologically. In a related study, the use of anatomical tract tracers in conjunction with EM-ICC will allow comparison of intracortical to thalamocortical connections. The research is expected to extend current knowledge of the mechanisms by which the cholinergic system modulates the formation of excitatory synapses. These mechanisms are likely to underlie the influence of states of sleep, wakefulness, attention and arousal on the processes of learning and memory formation.

描述（由申请人提供）：生命早期的感官体验通过尚未理解的细胞机制，导致突触连接的建立和完善。电子显微镜免疫细胞化学（EM-ICC）研究提供了有关发展皮质突触的分子组成的信息。但是，很难将这些信息与电生理研究的结果相关联。拟议的研究结合了电生理学，道追踪和EM-ICC的新型组合，以检查体感皮质中生理/解剖学上表征突触的分子组成。特别是，最近的证据表明，中央烟碱乙酰胆碱受体的活性对于兴奋性皮质突触的早期发展很重要。这些受体的存在将在鉴定的皮质神经元之间的突触中评估，在生理上确定了连接的成熟度。在一项相关研究中，使用解剖学示踪剂与EM-ICC结合使用，将允许对心脏内与丘脑皮质连接进行比较。预计该研究将扩展有关胆碱能系统调节兴奋性突触形成的机制的当前知识。这些机制可能是睡眠状态，清醒，注意力和唤醒对学习和记忆形成过程的影响。