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一个核心问题。越来越多的证据表明，除了LTP/LTD介导的神经元间突触连接强度的快速活动依赖性变化外，轴突、树突和棘的结构重塑也可能发生在成熟的大脑中，并可能通过皮层接线图的变化在更慢的时间尺度上促进长期记忆的巩固。重要的是，对于“基于体重”和“基于线路”的学习模式，随着衰老、疾病和智力迟钝而发生的锥体神经元形态和生物物理特性的变化，可能会降低相关大脑区域有效存储信息的能力，导致记忆缺陷和/或认知功能丧失。该合作项目包括对正常小鼠、老年小鼠和Ts65Dn小鼠进行协调实验和计算机模拟研究，其目标是使个体锥体神经元的形态和生物物理特性与成人大脑长期记忆功能和功能障碍之间的因果链更加丰富。

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.