Synaptic and intrinsic homeostatic mechanisms cooperate to increase L2/3 pyramidal neuron excitability during a late phase of critical period plasticity.
Synaptic and intrinsic homeostatic mechanisms cooperate to increase L2/3 pyramidal neuron excitability during a late phase of critical period plasticity.
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DOI：
10.1523/jneurosci.4502-12.2013
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发表时间：
2013-05-15
期刊：
影响因子：
--
通讯作者：
Turrigiano GG
中科院分区：
文献类型：
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作者：
Lambo ME;Turrigiano GG
视觉剥夺深刻地影响着视觉皮质反应特性，但这些变化背后的活动依赖可塑性机制却鲜为人知。单眼剥夺通过皮层兴奋性的双相改变引起眼优势(OD)的改变，首先降低对剥夺眼的反应性，然后缓慢增加对剥夺眼和备用眼的反应性。有人提出，这种缓慢的反应性增长是由于动态平衡突触伸缩，但这一预测尚未得到直接验证。结果表明，在大鼠单眼和双眼初级视皮层(V1m和V1b)，突触后2/3层(L2/3)锥体神经元的突触后强度受到MD的双向调节，首先在MD后1天和2天后净下降，3天后恢复到基线水平，最后在3天和6天之间经历净增强。这些突触变化的时间进程和方向与OD可塑性过程中视觉反应的已知变化很好地匹配。病毒介导的GluA2 C-Tail体内传递阻断了这些突触变化，这表明，与体外突触伸展一样，AMPA受体通过GluA2 C-Tail运输是突触后强度延迟增加所必需的。最后，我们还观察到延长MD后L2/3锥体神经元的内源性兴奋性延迟增加。这些数据表明，突触和内源性稳态机制协同作用增加延长MD后L2/3锥体神经元的兴奋性，并提示这些稳态机制有助于在外向可塑性过程中视觉反应的延迟获得。
Visual deprivation profoundly affects visual cortical response properties, but the activity-dependent plasticity mechanisms that underlie these changes are poorly understood. Monocular deprivation (MD) induces ocular dominance (OD) shifts through biphasic changes in cortical excitability, first decreasing responsiveness to the deprived eye, then slowly increasing responsiveness to both the deprived and spared eyes. It has been suggested that this slow gain of responsiveness is due to homeostatic synaptic scaling, but this prediction has not been tested directly. Here we show that, in rat monocular and binocular primary visual cortex (V1m and V1b), postsynaptic strength onto layer 2/3 (L2/3) pyramidal neurons is modulated in a biphasic manner by MD, first undergoing a net decrease after 1 and 2 days MD, increasing back to baseline after 3 days, and finally undergoing a net potentiation between 3 and 6 days. The time course and direction of these synaptic changes match well the known changes in visual responsiveness during OD plasticity. Viral-mediated delivery of the GluA2 C-tail in vivo blocked these synaptic changes, indicating that, like synaptic scaling in vitro, AMPA receptor trafficking via the GluA2 C-tail is required for the delayed increase in postsynaptic strength. Finally, we also observed a delayed increase in the intrinsic excitability of L2/3 pyramidal neurons following prolonged MD. These data indicate that synaptic and intrinsic homeostatic mechanisms cooperate to increase excitability of L2/3 pyramidal neurons following prolonged MD, and suggest that these homeostatic mechanisms contribute to the delayed gain of visual responsiveness during OD plasticity.