Axonal dynamics of excitatory and inhibitory neurons in somatosensory cortex.
Axonal dynamics of excitatory and inhibitory neurons in somatosensory cortex.
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DOI：
10.1371/journal.pbio.1000395
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发表时间：
2010-06-15
期刊：
影响因子：
9.8
通讯作者：
Gilbert CD
中科院分区：
文献类型：
--
作者：
Marik SA;Yamahachi H;McManus JN;Szabo G;Gilbert CD
电生理学——荧光病毒载体的传递——和双光子显微镜被用来证明啮齿类动物皮层 II/III 层兴奋性和抑制性神经元在感觉体验改变后的轴突重组的快速性。由于感觉剥夺，皮质地形可以被重新映射，这表明皮质回路会根据经验不断修改。为了观察感觉体验改变对皮质回路特定组成部分的影响，我们对拔胡须前后完整小鼠体感皮层中用转基因腺相关病毒标记的神经元进行了成像。拔胡须后，我们观察到兴奋性和抑制性神经元的轴突发生大规模且快速的重组，并伴随着布顿密度的短暂增加。对于兴奋性神经元的水平投影轴突，从非剥夺的胡须桶柱到剥夺的桶柱的轴突投影有净增加。位于被剥夺的晶须桶柱中的抑制性神经元的轴突侧枝在其体细胞附近收缩，并在其正常范围之外向非剥夺的晶须桶柱萌发长距离投射。这些结果表明，剥夺和非剥夺桶柱中兴奋和抑制平衡的改变是与感觉剥夺相关的地形重新映射的基础。成人大脑能够学习新任务并受到新经验的影响。成人大脑皮层的经验依赖性可塑性的证据可以在感觉输入皮质图的功能重新排列以及感觉体验改变后新连接的形成中看到。啮齿动物的桶状皮层接收来自胡须的感觉输入，是检查经验对皮层功能和电路影响的理想模型。在当前的研究中，我们通过在拔除胡须并因此去除其感觉输入之前和之后检查成年胡须桶皮层内的兴奋性和抑制性轴突来了解经验如何改变皮质回路。通过在细胞类型特异性启动子的控制下，将编码荧光蛋白的基因的传递与双光子成像相结合，我们能够直接检查轴突亚群，并确定成人活体大脑中特定连接何时以及在何种程度上发生改变。拔掉胡须后，我们观察到现有连接的收缩和新轴突的大量生长。轴突重建迅速发生，并在接下来的几周内继续发生变化，位于非剥夺皮层的兴奋性神经元的轴突和位于剥夺皮层的抑制性神经元的轴突相互萌芽。抑制回路的变化先于兴奋性连接的变化。
Electrophysiology-delivery of fluorescent viral vectors-and two-photon microscopy were used to demonstrate the rapidity of axonal restructuring of both excitatory and inhibitory neurons in rodent cortical layer II/III following alterations in sensory experience. Cortical topography can be remapped as a consequence of sensory deprivation, suggesting that cortical circuits are continually modified by experience. To see the effect of altered sensory experience on specific components of cortical circuits, we imaged neurons, labeled with a genetically modified adeno-associated virus, in the intact mouse somatosensory cortex before and after whisker plucking. Following whisker plucking we observed massive and rapid reorganization of the axons of both excitatory and inhibitory neurons, accompanied by a transient increase in bouton density. For horizontally projecting axons of excitatory neurons there was a net increase in axonal projections from the non-deprived whisker barrel columns into the deprived barrel columns. The axon collaterals of inhibitory neurons located in the deprived whisker barrel columns retracted in the vicinity of their somata and sprouted long-range projections beyond their normal reach towards the non-deprived whisker barrel columns. These results suggest that alterations in the balance of excitation and inhibition in deprived and non-deprived barrel columns underlie the topographic remapping associated with sensory deprivation. The adult brain is capable of learning new tasks and being shaped by new experiences. Evidence for experience-dependent plasticity of the adult cerebral cortex is seen in the functional rearrangement of cortical maps of sensory input and in the formation of new connections following alteration of sensory experience. The barrel cortex of the rodent receives sensory input from the whiskers and is an ideal model for examining the influence of experience on cortical function and circuitry. In the current study, we asked how experience alters cortical circuitry by examining excitatory and inhibitory axons within the adult whisker barrel cortex before and after plucking of a whisker and hence removal of its sensory input. By combining delivery of genes encoding fluorescent proteins, under the control of cell-type specific promoters, with two-photon imaging, we were able to directly examine subpopulations of axons and to determine when and to what extent experience altered specific connections in the adult living brain. Following whisker plucking we observed both the retraction of existing connections and an exuberant amount of growth of new axons. Axonal restructuring occurred rapidly and continued to undergo changes over the following weeks, with reciprocal sprouting of axons of excitatory neurons located in non-deprived cortex and of inhibitory neurons located in deprived cortex. The changes in the inhibitory circuits preceded those seen for excitatory connections.
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