Dendritic BDNF synthesis is required for late-phase spine maturation and recovery of cortical responses following sensory deprivation.
Dendritic BDNF synthesis is required for late-phase spine maturation and recovery of cortical responses following sensory deprivation.
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DOI：
10.1523/jneurosci.4462-11.2012
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发表时间：
2012-04-04
期刊：
影响因子：
--
通讯作者：
Xu B
中科院分区：
文献类型：
--
作者：
Kaneko M;Xie Y;An JJ;Stryker MP;Xu B
出生后早期的感觉经验塑造了大脑中的神经元连接。在这里，我们报告的局部合成的脑源性神经营养因子（BDNF）的树突在这一过程中起着重要的作用。我们发现，树突棘层2/3锥体神经元的视皮层突变小鼠缺乏树突状BDNF mRNA，因此当地BDNF的合成是正常的3周龄，但更薄，更长，更紧密地间隔（形态特征的不成熟）在4个月的年龄比野生型（WT）的同窝仔。在两个年龄段，这些突变动物的视觉皮层的2/3层也有较少的GABA能突触前末梢。然而，在两个年龄段的突变体和WT小鼠中，树突状动脉的总体大小和形状相似。通过使用内部信号的光学成像和单单位记录，我们发现突变动物在关键期内单眼剥夺（MD）后未能恢复皮层反应性，尽管它们通常表现出对短暂剥夺视觉的眼睛的反应性的竞争性丧失。此外，MD仍然诱导成年突变小鼠对闭眼的反应性丧失，但在成年野生型小鼠中没有。这些结果表明，树突状BDNF的合成所需的脊髓修剪，后期脊髓成熟，和恢复皮层反应后感觉剥夺。他们还表明，成年后感觉剥夺后，树突棘的成熟是维持皮质反应所必需的。
Sensory experience in early postnatal life shapes neuronal connections in the brain. Here we report that the local synthesis of brain-derived neurotrophic factor (BDNF) in dendrites plays an important role in this process. We found that dendritic spines of layer 2/3 pyramidal neurons of the visual cortex in mutant mice lacking dendritic Bdnf mRNA and thus local BDNF synthesis were normal at 3 weeks of age, but thinner, longer, and more closely spaced (morphological features of immaturity) at 4 months of age than in wild-type (WT) littermates. Layer 2/3 of the visual cortex in these mutant animals also had fewer GABAergic presynaptic terminals at both ages. The overall size and shape of dendritic arbors were, however, similar in mutant and WT mice at both ages. By using optical imaging of intrinsic signals and single-unit recordings, we found that mutant animals failed to recover cortical responsiveness following monocular deprivation (MD) during the critical period, although they displayed normally the competitive loss of responsiveness to an eye briefly deprived of vision. Furthermore, MD still induced a loss of responsiveness to the closed eye in adult mutant mice, but not in adult wild-type mice. These results indicate that dendritic BDNF synthesis is required for spine pruning, late-phase spine maturation, and recovery of cortical responsiveness following sensory deprivation. They also suggest that maturation of dendritic spines is required for the maintenance of cortical responsiveness following sensory deprivation in adulthood.