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未被理解的细胞机制导致突触连接的建立和完善。电镜免疫细胞化学（EM-ICC）研究提供了有关发育中的皮质突触分子组成的信息。然而，很难将这些信息与电生理研究的结果联系起来。本研究将电生理学、神经束追踪和EM-ICC结合起来，研究躯体感觉皮层中具有生理/解剖特征的突触的分子组成。特别是，最近的证据表明，中枢烟碱乙酰胆碱受体的活性对兴奋性皮层突触的早期发育很重要。这些受体的存在将在确定的皮质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，将解剖束示踪剂与EM-ICC结合使用，可以比较皮质内与丘脑皮质的连接。这项研究有望扩展目前对胆碱能系统调节兴奋性突触形成的机制的了解。这些机制可能是睡眠、清醒、注意力和觉醒状态对学习和记忆形成过程影响的基础。

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.