Ma W, Behar T, Barker J L
Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892.
J Comp Neurol. 1992 Nov 8;325(2):271-90. doi: 10.1002/cne.903250210.
The development of GABAergic neurons in the spinal cord of the rat has been investigated by immunocytochemical staining of frozen sections with anti-gamma-aminobutyric acid (GABA) antiserum. In the cervical cord, GABA-immunoreactive fibers first appeared at embryonic day (E) 13 in the presumptive white matter within the ventral commissure, ventral funiculus, and dorsal root entrance zone, and in the ventral roots. There were no GABA-immunoreactive cell bodies detected at this age. By E14, motoneurons, the earliest generated spinal cells, were the first cell population to become GABA-immunoreactive at the cell body level. Thereafter, GABA-immunoreactive neurons increased progressively in number and extended from ventral to dorsal regions. GABA-immunoreactive relay neurons within lamina I of the dorsal horn were initially detected at E17. Interneurons in the substantia gelatinosa, the latest generated cells in the spinal cord, were also the last to express the GABA immunoreactivity at E18. Immunoreactive neurons peaked in intensity and extent at E18 and 19. GABA immunoreactivity was only detectable in neurons within the intermediate and marginal zones 1-3 days after they withdrew from the cell cycle. This contrasts to glutamate decarboxylase immunoreactivity, which is detected in precursor cells in the ventricular zone prior to, or during, withdrawal from the cell cycle. Toward the end of gestation, GABA immunoreactivity declined in intensity and extent. This regression began in the ventral horn of the cervical region and ended in the dorsal horn of the lumbosacral region. During the first week after birth, immunoreactivity in motoneurons and in many other neurons within the ventral horn, intermediate gray, and deeper layers of the dorsal horn disappeared, and only in those neurons predominantly within the superficial layers of the dorsal horn did it persist into adulthood. Thus, the expression and regression of GABA immunoreactivity in the spinal cord followed ventral-to-dorsal, rostral-to-caudal, and medial-to-lateral gradients. These observations indicate that the majority of embryonic spinal neurons pass through a stage of transient expression of GABA immunoreactivity. The functional significance of this transient expression is unknown, but it coincides with the period of intense neurite growth of motoneurons, sensory neurons, and interneurons, and of neuromuscular junction formation, suggesting that the transient presence of GABA may play an important role in the differentiation of sensorimotor neuronal circuits.
通过用抗γ-氨基丁酸（GABA）抗血清对大鼠脊髓冰冻切片进行免疫细胞化学染色，研究了大鼠脊髓中GABA能神经元的发育情况。在颈髓中，GABA免疫反应性纤维最早在胚胎第13天出现在腹侧连合、腹侧索和背根进入区的假定白质以及腹侧根中。在这个年龄段未检测到GABA免疫反应性细胞体。到胚胎第14天，最早产生的脊髓细胞运动神经元是在细胞体水平上第一个变得具有GABA免疫反应性的细胞群体。此后，GABA免疫反应性神经元数量逐渐增加，并从腹侧扩展到背侧区域。背角I层内的GABA免疫反应性中继神经元最初在胚胎第17天被检测到。脊髓中最晚产生的细胞——胶状质中的中间神经元，也是在胚胎第18天最后表达GABA免疫反应性的。免疫反应性神经元在胚胎第18天和19天强度和范围达到峰值。GABA免疫反应性仅在中间和边缘区的神经元退出细胞周期1 - 3天后才能检测到。这与谷氨酸脱羧酶免疫反应性形成对比，谷氨酸脱羧酶免疫反应性在细胞周期退出之前或期间在脑室区的前体细胞中就能检测到。在妊娠末期，GABA免疫反应性在强度和范围上下降。这种消退从颈区腹角开始，在腰骶区背角结束。在出生后的第一周内，运动神经元以及腹角、中间灰质和背角深层的许多其他神经元中的免疫反应性消失，只有背角浅层的那些神经元的免疫反应性持续到成年。因此，脊髓中GABA免疫反应性的表达和消退遵循从腹侧到背侧、从嘴侧到尾侧以及从中线到外侧的梯度。这些观察结果表明，大多数胚胎脊髓神经元都经历了一个GABA免疫反应性短暂表达的阶段。这种短暂表达的功能意义尚不清楚，但它与运动神经元、感觉神经元和中间神经元强烈的神经突生长以及神经肌肉接头形成的时期相吻合，这表明GABA的短暂存在可能在感觉运动神经元回路的分化中起重要作用。
