Molecular mechanisms of adult cortical plasticity

 描述（由申请人提供）：成人大脑皮层能够经历经验依赖性功能变化。这些变化在CNS损伤后的知觉学习和功能恢复中起作用。成年人皮层可塑性的通路包括皮层锥体细胞形成的长距离水平连接丛和抑制性中间神经元形成的连接。这种回路中的经验依赖性变化涉及新轴突连接的萌芽和预先存在的连接的修剪。该项目涉及研究轴突乔木重塑的分子基础，包括神经营养因子的信号传导和caspase依赖的凋亡途径。使用成年人皮质可塑性的小鼠模型，包括拔须后体感皮质的重新映射和皮质轴突的2-光子体内纵向成像，将确定轴突修剪和生长过程中这些信号通路中不同组分的作用。这些实验旨在绘制从神经活动模式改变到皮层回路改变的步骤和分子相互作用。

 DESCRIPTION (provided by applicant): The adult cerebral cortex is capable of undergoing experience dependent functional changes. Such changes play a role in perceptual learning and recovery of function following CNS damage. The circuitry mediating adult cortical plasticity includes the plexus of long range horizontal connections formed by cortical pyramidal cells as well as the connections formed by inhibitory interneurons. The experience dependent changes in this circuitry involve the sprouting of new axonal connections and the pruning of preexisting connections. The proposed project involves investigating the molecular basis for the remodeling of axonal arbors, including signaling by neurotrophins and the caspase dependent apoptotic pathway. Using a mouse model of adult cortical plasticity involving remapping of the somatosensory cortex following whisker plucking and 2- photon in vivo longitudinal imaging of cortical axons, the role of different components in these signaling pathways in the process of axonal pruning and outgrowth will be determined. The experiments are designed to map the steps and molecular interactions leading from alterations in the patterns of neural activity to alterations in cortical circuits.