Anatomical, Physiological, and Modeling Studies of Memory-Related Neural Form and Function

确定长期记忆是如何在成人大脑中编码的，仍然是神经科学的核心问题。越来越多的证据表明，除了LTP/LTD介导的神经元之间突触连接强度的快速活动依赖变化外，轴突、树突和棘突的结构性重构也可以发生在成熟的大脑中，并可能通过在慢得多的时间尺度上改变皮质连接图来促进长期记忆的巩固。重要的是，无论是基于重量的学习模式还是基于网络的学习模式，随着年龄、疾病和智力低下而发生的锥体神经元形态和生物物理特性的变化可能会降低相关脑区有效存储信息的能力，导致记忆障碍和/或认知功能的丧失。这个合作项目的目标是充实将单个锥体神经元的形态和生物物理特性与成人大脑的长期记忆功能和功能障碍联系起来的因果链条，包括在正常、老年和Ts65Dn小鼠身上进行协调的实验和计算机模拟研究。

To determine how long-term memories are encoded in the adult brain remains a central problem of neuroscience. Growing evidence suggests that in addition to fast activity-dependent changes in the strengths of synaptic connections between neurons mediated by LTP/LTD, structural remodeling of axons, dendrites, and spines can also occur in the mature brain, and may contribute to the consolidation of long-term memories through changes in the cortical wiring diagram on a much slower time scale. Importantly, for both "weight based" and "wiring based" modes of learning, changes in the morphological and biophysical properties of pyramidal neurons that occur with aging, disease and mental retardation could reduce the capacity of the associated brain areas to store information effectively, leading to memory deficits and/or loss of cognitive function. The goal of this collaborative project, involving coordinated experimental and computer simulation studies in normal, aged, and Ts65Dn mice, is to flesh out the causal chain that links the morphological and biophysical properties of individual pyramidal neurons to long-term memory function and dysfunction in the adult brain.