Higo Noriyuki, Oishi Takao, Yamashita Akiko, Murata Yumi, Matsuda Keiji, Hayashi Motoharu
Neuroscience Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Umezono, Tsukuba, Ibaraki, Japan.
Brain Res. 2007 Sep 26;1171:30-41. doi: 10.1016/j.brainres.2007.07.054. Epub 2007 Aug 8.
To understand the molecular and cellular bases of plasticity in the primate motor cortex, we investigated the expression of three protein kinase-C (PKC) substrates: GAP-43, myristoylated alanine-rich C-kinase substrate (MARCKS), and neurogranin, which are key molecules regulating synaptic plasticity. Prominent signals for the three mRNAs were primarily observed in pyramidal cells. Large pyramidal cells in layer V, from which the descending motor tract originates, contained weaker hybridization signals for GAP-43 and neurogranin mRNAs than did the smaller pyramidal cells. We also performed double-label in situ hybridization showing that GAP-43 and neurogranin mRNAs were expressed in a subset of MARCKS-positive neurons. Quantitative analysis showed that the expression was different between the layers: layer VI contained the strongest and layer II the weakest signals for all three mRNAs. The expression levels of GAP-43 and MARCKS mRNA in layer V were higher than in layer III, while the expression level of neurogranin mRNA in layer V was almost the same as in layer III. Developmental analysis from the newborn to adult indicated that the expression levels of the three mRNAs were higher in the infant motor cortex than in the adult. The expression of both GAP-43 and neurogranin mRNAs transiently increased over several months postnatally. The present study showed that the expression of the three PKC substrates was specific to cell types, cortical layers, and postnatal developmental stage. The specific expression may reflect functional specialization for plasticity in the motor cortex of both infants and adults.
为了解灵长类动物运动皮层可塑性的分子和细胞基础,我们研究了三种蛋白激酶-C(PKC)底物的表达:生长相关蛋白43(GAP-43)、豆蔻酰化富含丙氨酸的蛋白激酶C底物(MARCKS)和神经颗粒素,它们是调节突触可塑性的关键分子。三种mRNA的显著信号主要在锥体细胞中观察到。下行运动束起源的V层大锥体细胞中,GAP-43和神经颗粒素mRNA的杂交信号比小锥体细胞中的弱。我们还进行了双重原位杂交,结果显示GAP-43和神经颗粒素mRNA在MARCKS阳性神经元的一个子集中表达。定量分析表明,各层之间的表达存在差异:所有三种mRNA在VI层的信号最强,在II层的信号最弱。V层中GAP-43和MARCKS mRNA的表达水平高于III层,而V层中神经颗粒素mRNA的表达水平与III层几乎相同。从新生儿到成年的发育分析表明,婴儿运动皮层中这三种mRNA的表达水平高于成年人。出生后几个月内,GAP-43和神经颗粒素mRNA的表达均短暂增加。本研究表明,三种PKC底物的表达具有细胞类型、皮层层和出生后发育阶段的特异性。这种特异性表达可能反映了婴儿和成年人运动皮层可塑性的功能特化。