Imaging experience-dependent spine plasticity in vivo

描述（由申请人提供）：大脑是如何随着经历而变化的？一旦大脑成熟，它能通过新突触的生长和旧突触的丧失来重新连接吗？测量脊柱密度或突触数量的经典研究依赖于死后技术，不能直接观察脊柱的生长和丧失。最近，利用荧光蛋白转基因动物的双光子显微镜，可以跟踪动物数周到数月的树突和脊柱。该项目的目的是描述感官体验变化对桶状皮质第V层和第I层I/I 11神经元的树突和脊柱持久性的长期影响。在被剥夺的桶状柱中观察到感受野的可塑性，对被剥夺的须的反应在几天内变得压抑，而对相邻的未被剥夺的须的反应在1-3周后增强。目前尚不清楚这两个过程是否涉及突触的形成或丧失。利用野生型和alphaCamKIIT286A（感受野可塑性受损）小鼠的长期体内成像和电子显微镜，我们将记录正常情况下和棋盘须剥夺后1- 3周突触的丢失和形成。

DESCRIPTION (provided by applicant): How does the brain change with experience? Once the brain is mature, can it be rewired by growth of new synapses and loss of older ones? Classic studies measuring spine densities or synapse numbers have relied on post-mortem techniques which do not allow direct observation of spine growth and loss. Recently, 2-photon microscopy in fluorescent protein transgenic animals has made it possible to follow dendrites and spines over weeks to months of an animal's life. The aim of the project will be to describe the long-term effect of sensory experience changes on dendrite and spine persistence in layer V and layer I I/I 11 neurons of the barrel cortex. Receptive field plasticity has been observed in deprived barrel columns where responses to deprived whiskers become depressed within days and responses to adjacent spared whiskers are enhanced 1-3 weeks later. It is not known if either process involves the formation or loss of synapses. Using long-term in vivo imaging and electron microscopy in wild-type and alphaCamKIIT286A (receptive field plasticity impaired) mice, we will document the loss and formation of synapses that occur normally and 1- 3 weeks after chessboard whisker deprivation.