CNR Neuroscience Institute, 56124 Pisa, Italy.
J Neurosci. 2011 Oct 19;31(42):15163-72. doi: 10.1523/JNEUROSCI.2617-11.2011.
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.
年龄依赖性可塑性的一个经典例子是眼优势（OD）可塑性，由单眼剥夺（MD）触发。皮质电路对短暂 MD 时期的敏感性在幼年动物中最大，并在成年时下调。目前尚不清楚生理可塑性下调是否是成年后形态重塑潜力降低的原因。在这里，我们已经测试了刺激结构重排是否能有效促进成年期的经验依赖性可塑性。我们利用了一种细菌蛋白毒素，细胞毒性坏死因子 1（CNF1），它通过持续激活 Rho GTPases 来调节神经元过程中的肌动蛋白动力学和结构。将 CNF1 注射到成年大鼠的视皮层中会引发 Rho GTPase Rac1 的持久激活，从而导致锥体神经元的棘突密度和长度增加。用 CNF1 处理的成年大鼠在 MD 后表现出 OD 向睁眼的偏移，而对照大鼠则没有。CNF1 介导的 OD 可塑性选择性归因于睁眼反应的增强，而闭眼输入不受影响。这种效应与单眼剥夺、CNF1 处理大鼠 IV 层中的膝状皮质末端密度增加相关。因此，Rho GTPase 的激活通过增强来自睁眼的更活跃输入，在成年皮质中重新建立 OD 可塑性。这些数据在体内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 GTPases 在大脑可塑性中的作用。Rho GTPase 激活的塑性作用可能被用来促进大脑修复。
