Imaging experience-dependent spine plasticity in vivo

描述（由申请人提供）：大脑如何随着经验而变化？一旦大脑成熟，它是否可以通过新突触的生长和旧突触的丢失来重新连接？测量棘密度或突触数量的经典研究依赖于死后技术，这些技术不允许直接观察棘的生长和损失。最近，在荧光蛋白转基因动物的双光子显微镜已经有可能在几周到几个月的动物的生活树突和棘。该项目的目的是描述感觉经验的变化对树突和棘的持久性在层V和层I I/I 11神经元的桶皮质的长期影响。在被剥夺的桶柱中观察到了感受野的可塑性，其中对被剥夺的胡须的反应在几天内变得压抑，而对相邻的备用胡须的反应在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。在野生型和alphaCamKIIT 286 A（感受野可塑性受损）小鼠中使用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周发生的突触的丢失和形成。

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.