Experience-dependent pruning of dendritic spines in visual cortex by tissue plasminogen activator
Experience-dependent pruning of dendritic spines in visual cortex by tissue plasminogen activator
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DOI：
10.1016/j.neuron.2004.11.028
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发表时间：
2004-12-16
期刊：
影响因子：
16.2
通讯作者：
Hensch, TK
中科院分区：
文献类型：
--
作者：
Mataga, N;Mizuguchi, Y;Hensch, TK
感官体验通过未知的过程在出生后早期对大脑进行物理上的重新连接。在这里，我们确定了视觉皮层 II/III 层单眼剥夺 (MD) 的一个强大的解剖学后果，对应于轴突输入任何变化之前反应能力的快速、功能性丧失。睁眼后锥体细胞顶端树突上的突起稳定增加，但仅在生理关键期短暂MD后通过竞争机制短暂消失。相反，组织型纤溶酶原激活剂 (tPA) 的蛋白水解作用随着年龄的增长而下降，并且仅在年轻小鼠中随着 MD 的增加而增加。谷氨酸脱羧酶 (GAD65) 有针对性地破坏 tPA 释放或其上游调节，可防止 MD 引起的脊柱损失，这种损失可在关键期可塑性的同时通过药物来挽救。在正确检测到竞争性输入后，结构重塑的细胞外机制仅限于双眼区域，从而将早期感觉体验与视觉功能联系起来。
Sensory experience physically rewires the brain in early postnatal life through unknown processes. Here, we identify a robust anatomical consequence of monocular deprivation (MD) in layer II/III of visual cortex that corresponds to the rapid, functional loss of responsiveness preceding any changes in axonal input. Protrusions on pyramidal cell apical dendrites increased steadily after eye opening, but were transiently lost through competitive mechanisms after brief MD only during the physiological critical period. Proteolysis by tissue-type plasminogen activator (tPA) conversely declined with age and increased with MD only in young mice. Targeted disruption of tPA release or its upstream regulation by glutamic acid decarboxylase (GAD65) prevented MD-induced spine loss that was pharmacologically rescued concomitant with critical period plasticity. An extracellular mechanism for structural remodeling that is limited to the binocular zone upon proper detection of competing inputs thus links early sensory experience to visual function.