Specificity of Synapse Formation

人类大脑的认知依赖于脑细胞(神经元)之间异常精确的连接。如果神经通路没有正确形成或受损，那么大脑功能将不可避免地受到损害。尽管人们对组成脑细胞(突触)之间连接的分子有很多了解，但对引导特定神经元指向其正确目标的分子标记只有初步的了解。这个项目的目标是使用电生理、分子和免疫细胞化学方法来识别指定脑细胞之间选择性突触连接的分子。要研究的大脑区域是海马体，这是一种已知对包括人类在内的所有哺乳动物的学习和记忆都很重要的结构。海马体是高度组织化的，不同的细胞群体之间有着清晰的连接模式。最初的重点将是建立在初步数据的基础上，这些数据表明潜在的“路标”分子显示了细胞类型特定的分布模式。随后的实验将操纵这些分子，直接测试它们在指导特定细胞群体之间突触形成方面的作用。在这项工作的所有方面都将鼓励学生参与，结果将在公开会议和科学出版物上传播。这些研究的意义和影响是显而易见的。为了充分了解整个动物界的胚胎和幼小生物体中大脑是如何形成的，必须获得关于单个细胞如何能够寻找并与正确的目标形成突触的基本知识。这里所述的工作将为实现这一目标作出重要贡献。

Cognition in the human brain depends upon extraordinarily precise connections between brain cells (neurons). If neural pathways do not form correctly or become damaged, then impairments of brain function will inevitably result. Although a great deal is known about molecules that comprise connections between brain cells (synapses) there is only a rudimentary understanding of the molecular markers that direct any particular neuron to its correct target destination. The goal of this project is employ electrophysiological, molecular, and immunocytochemical approaches to identify molecules that specify selective synaptic connectivity between brain cells. The brain area to be studied is the hippocampus, a structure known to be important for learning and memory in all mammals, including humans. The hippocampus is highly organized, with clear patterns of connectivity between distinct cell populations. The initial focus will be to build upon preliminary data which indicate that potential "signpost" molecules show cell-type specific distribution patterns. Subsequent experiments will manipulate these molecules to test directly their role in directing synapse formation between specific populations of cells. Student participation will be encouraged throughout all aspects of this work and results will be disseminated at public meetings and via scientific publications. The significance and impact of these studies is clear. In order to fully understand how brains form in embryos and young organisms throughout the animal kingdom, fundamental knowledge must be obtained about how individual cells are able to seek out and form synapses with their correct targets. The work described here will make an important contribution to achieving that goal.