Jakowec M W, Yen L, Kalb R G
Department of Neurology, Yale University School of Medicine, New Haven, CT 06510, USA.
Neuroscience. 1995 Aug;67(4):909-20. doi: 10.1016/0306-4522(95)00094-y.
In early postnatal life the acquisition of mature morphological and molecular features of motor neurons is influenced by synaptic activity within the spinal cord. Glutamatergic synaptic neurotransmission is believed to play a central role in this process. We hypothesize that the repertoire of glutamate receptors expressed by neurons in the young spinal cord differ from those expressed in adults and such receptors support activity-dependent developmental plasticity. To explore this idea, we used in situ hybridization histochemistry to determine the distribution, temporal expression, and potential subunit composition of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors in the developing rat spinal cord and compared these findings with those in adult rats. We find qualitative and quantitative changes in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit gene expression over the first month of postnatal life. alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit genes GluR1, 2 and 4 are expressed at greater levels throughout the spinal cord of the neonate versus the adult animals. The developmental down-regulation is most pronounced for GluR1 transcripts, less for GluR2 and GluR4 transcripts, and minimal for GluR3 transcripts. Analysis of flip and flop splice variants of each subunit show that receptors expressed by adult motor neurons are potentially composed of the subunits GluR1 flop, GluR2 flip, GluR3 flip and flop, and GluR4 flip. In neonatal motor neuron all subunits are potentially expressed (except GluR2 flop) with quantitatively the dominent subunits being the flip splice variants of GluR1, 2 and 4. Receptors in the substantia gelatinosa undergo equally dramatic, developmentally independent changes. Changes in the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit composition are likely to have an important effect on the electrophysiological properties of motor neurons and may form part of the molecular identity of neurons capable of undergoing activity-dependent developmental plasticity.
在出生后的早期生活中，运动神经元成熟形态和分子特征的获得受脊髓内突触活动的影响。谷氨酸能突触神经传递被认为在此过程中起核心作用。我们推测，幼龄脊髓中神经元表达的谷氨酸受体库与成年动物不同，且此类受体支持依赖活动的发育可塑性。为探究这一观点，我们采用原位杂交组织化学方法，确定发育中大鼠脊髓内α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体的分布、时间表达及潜在亚基组成，并将这些结果与成年大鼠的结果进行比较。我们发现，在出生后第一个月内，α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体亚基基因表达存在质和量的变化。与成年动物相比，α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体亚基基因GluR1、2和4在新生动物整个脊髓中的表达水平更高。GluR1转录本的发育性下调最为明显，GluR2和GluR4转录本的下调程度较小，而GluR3转录本的下调程度最小。对每个亚基的翻转和摆动剪接变体的分析表明，成年运动神经元表达的受体可能由GluR1摆动、GluR2翻转、GluR3翻转和摆动以及GluR4翻转亚基组成。在新生运动神经元中，所有亚基均可能表达（GluR2摆动除外），数量上占主导的亚基是GluR1、2和4的翻转剪接变体。胶状质中的受体也经历同样显著的、与发育无关的变化。α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体亚基组成的变化可能对运动神经元的电生理特性产生重要影响，并可能构成能够经历依赖活动的发育可塑性的神经元分子特性的一部分。
