Activation of Rho GTPases Triggers Structural Remodeling and Functional Plasticity in the Adult Rat Visual Cortex
Activation of Rho GTPases Triggers Structural Remodeling and Functional Plasticity in the Adult Rat Visual Cortex
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DOI：
10.1523/jneurosci.2617-11.2011
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发表时间：
2011-10-19
影响因子：
5.3
通讯作者：
Caleo, Matteo
中科院分区：
文献类型：
--
作者：
Cerri, Chiara;Fabbri, Alessia;Caleo, Matteo
年龄依赖性可塑性的一个经典例子是由单眼剥夺（MD）触发的眼优势（OD）可塑性。皮层电路的敏感性，以短暂的MD是最大的少年动物和下调成年年龄。目前尚不清楚是否减少的形态重塑潜力的基础，这种下调的生理可塑性在成年期。在这里，我们已经测试了刺激结构重排是否有效地促进经验依赖的可塑性在成年年龄。我们已经利用了细菌蛋白毒素，细胞毒性坏死因子1（CNF1），调节肌动蛋白动力学和结构的神经过程通过持续激活的Rho GTPases。将CNF1注射到成年大鼠的视皮层中，引发了Rho GTTRac Rac 1的长期激活，从而增加了锥体神经元的棘密度和长度。用CNF1处理的成年大鼠，但不是对照组，在MD后显示OD向睁开的眼睛偏移。CNF1介导的OD可塑性选择性地归因于睁眼反应的增强，而闭眼输入不受影响。这种效果与增加的密度在单眼剥夺，CNF1治疗的大鼠第四层的膝状皮质终端。因此，Rho GT3激活通过增强来自睁开的眼睛的更活跃的输入来恢复成人皮质中的OD可塑性。这些数据建立了结构重塑和功能可塑性之间的直接联系，并证明了Rho GTP酶在体内脑可塑性中的作用。Rho GT3激活的增塑作用可用于促进脑修复。
A classical example of age-dependent plasticity is ocular dominance (OD) plasticity, triggered by monocular deprivation (MD). Sensitivity of cortical circuits to a brief period of MD is maximal in juvenile animals and downregulated in adult age. It remains unclear whether a reduced potential for morphological remodeling underlies this downregulation of physiological plasticity in adulthood. Here we have tested whether stimulation of structural rearrangements is effective in promoting experience-dependent plasticity in adult age. We have exploited a bacterial protein toxin, cytotoxic necrotizing factor 1 (CNF1), that regulates actin dynamics and structure of neuronal processes via a persistent activation of Rho GTPases. Injection of CNF1 into the adult rat visual cortex triggered a long-lasting activation of the Rho GTPase Rac1, with a consequent increase in spine density and length in pyramidal neurons. Adult rats treated with CNF1, but not controls, showed an OD shift toward the open eye after MD. CNF1-mediated OD plasticity was selectively attributable to the enhancement of open-eye responses, whereas closed-eye inputs were unaffected. This effect correlated with an increased density of geniculocortical terminals in layer IV of monocularly deprived, CNF1-treated rats. Thus, Rho GTPase activation reinstates OD plasticity in the adult cortex via the potentiation of more active inputs from the open eye. These data establish a direct link between structural remodeling and functional plasticity and demonstrate a role for Rho GTPases in brain plasticity in vivo. The plasticizing effects of Rho GTPase activation may be exploited to promote brain repair.