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早期产后生命中物理重新整理大脑。1）我们确定了视觉皮层的第2/3层单眼剥夺（MD）的强大解剖学后果，这与轴突输入中任何变化之前的任何变化之前的快速，功能丧失相对应。锥体细胞顶端树突上的突起睁大眼睛稳定增加，但在物理关键时期短暂的MD之后，通过竞争机制瞬间损失。组织型纤溶酶原激活因子（TPA）的蛋白水解随着年龄的增长而下降，仅在年轻小鼠中增加了MD。针对TPA释放的有针对性破坏或通过谷氨酸脱羧酶（GAD65）对上游调节的上游调节，可以防止MD脊柱损失，而MD在药理上挽救了与关键时期可塑性同时拯救的脊柱损失。囊泡谷氨酸转运蛋白（VGLUT）1和VGLUT2。在CP期间，VGLUT2的免疫反应性通过短暂的单眼剥夺（4DMD）降低。有趣的是，与4DMD相比，对侧BZ中所有层中的两个信号均低于闭合眼睛的闭合眼睛的闭合眼，这会影响功能转移和树突快速细化的效果更强。这些结果表明，兴奋性输入的快速和局部功能丧失可能与经验依赖性竞争修剪的树突状脊柱相关。3）我们检查了TPA在细胞外基质（ECM）上的特定作用。与Wilderia floribunda凝集素（WFA）结合的生周神经元网通常出现在成人野生型（WT）和TPA KO小鼠中，主要是双眼区（BZ）的第IVN层。通过活性酶纤溶酶以剂量和时间依赖性的方式观察到细胞外蛋白的有限蛋白水解。较少的