Cholinergic modulation of excitatory synapse formation

描述（由申请人提供）：生命早期的感觉体验通过尚不清楚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）研究提供了信息的分子组成的发展皮层突触。然而，很难将这些信息与电生理学研究的结果相关联。拟议的研究使用一种新的组合电生理学，跟踪和EM-ICC检查生理/解剖特征的突触在体感皮层的分子组成。特别是，最近的证据表明，中央烟碱乙酰胆碱受体的活动是重要的兴奋性皮层突触的早期发展。这些受体的存在将在已鉴定的皮层神经元之间的突触中进行评估，其中连接的成熟度已在生理学上确定。在一项相关研究中，使用解剖束示踪剂结合EM-ICC将允许比较皮质内与丘脑皮质的连接。这项研究有望扩展胆碱能系统调节兴奋性突触形成机制的现有知识。这些机制可能是睡眠、觉醒、注意力和觉醒状态对学习和记忆形成过程的影响的基础。

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.