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The role of serine proteases in synaptic plasticity of mouse visual cortex

丝氨酸蛋白酶在小鼠视觉皮层突触可塑性中的作用

基本信息

批准号：
16500211
负责人：
MATAGA Nobuko
金额：
$ 2.3万
依托单位：
The Institute of Physical and Chemical Research
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

项目摘要

Sensory experience physically rewires the brain in early postnatal life through unknown processes.1) We identified a robust anatomical consequence of monocular deprivation (MD) in layer 2/3 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 during the physiological critical period. Proteolysis by tissue-type plasminogen activator (tPA) conversely declined with age and increased upon MD only in young mice. Targeted disruption of tPA release or its upstream regulation by glutamic acid decarboxylase (GAD65) prevented spine loss by MD that was pharmacologically rescued concomitant with critical period plasticity.2) To explore correspondingly rapid and local pre-synaptic refinements by sensory deprivation, excitatory intracortical or thalamocortical axon terminals wer … More e visualized in the BZ by vesicular glutamate transporters (vGlut)1 and vGlut2, respectively. The immunoreactivity of vGlut2 decreased around layer IV by brief monocular deprivation (4dMD) during the CP. Interestingly, both signals in all layers were lower in the contralateral BZ to the closed eye than that in the ipsilateral BZ by TTX injections, that induces stronger effect in functional shifts and rapid dendritic refinement compared to 4dMD. These results suggest that rapid and local functional loss of excitatory inputs may correlate with dendritic spine pruning by experience-dependent competition.3) We examined a specific role for tPA upon the extracellular matrix (ECM). Perineuronal nets bound to wisteria floribunda agglutinin (WFA) appeared normally in adult wild-type (WT) and tPA KO mice, primarily in layer IVN of the binocular zone (BZ).4) We explored potential substrates for tPA-mediated proteolysis in mouse visual cortex. Limited proteolysis of extracellular proteins was observed in a dose-and time-dependent manner by active enzyme plasmin. Less

感官体验通过未知的过程在出生后早期物理地重新连接大脑。1）我们在视觉皮层的2/3层中确定了单眼剥夺（MD）的强大解剖学后果，其对应于轴突输入的任何变化之前的快速功能性反应丧失。锥体细胞顶树突上的突起在睁眼后稳步增加，但在生理关键期短暂MD后通过竞争机制短暂丢失。相反，组织型纤溶酶原激活剂（tPA）的蛋白水解随着年龄的增长而下降，并在年轻小鼠的MD增加。通过谷氨酸脱羧酶（GAD 65）靶向破坏tPA释放或其上游调节，可以防止MD引起的脊髓缺失，而MD是伴随着关键期可塑性而被挽救的。2）为了探索通过感觉剥夺引起的相应的快速和局部突触前精细化，兴奋性皮质内或丘脑皮质轴突终末被发现。 ...更多信息分别通过囊泡谷氨酸转运体（vGlut）1和vGlut 2在BZ中可见。vGlut 2的免疫反应性下降周围IV层的短暂单眼剥夺（4dMD）在CP。有趣的是，所有层中的两个信号在对侧BZ中均低于TTX注射的同侧BZ中的信号，这诱导了与4dMD相比更强的功能转移和快速树突细化的效果。这些结果表明，快速和局部功能的兴奋性输入的损失可能与树突棘修剪经验依赖性竞争。3）我们研究了一个特定的作用，tPA的细胞外基质（ECM）。与紫藤凝集素（WFA）结合的神经元周网在成年野生型（WT）和tPA KO小鼠中正常出现，主要在双眼带（BZ）的IVN层。通过活性酶纤溶酶以剂量和时间依赖性方式观察到细胞外蛋白的有限蛋白水解。少