McIntire S L, Jorgensen E, Kaplan J, Horvitz H R
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, 02139.
Nature. 1993 Jul 22;364(6435):337-41. doi: 10.1038/364337a0.
gamma-Aminobutyric acid (GABA) is the most abundant inhibitory neurotransmitter in vertebrates and invertebrates. GABA receptors are the target of anxiolytic, antiepileptic and antispasmodic drugs, as well as of commonly used insecticides. How does a specific neurotransmitter such as GABA control animal behaviour? To answer this question, we identified all neurons that react with antisera raised against the neurotransmitter GABA in the nervous system of the nematode Caenorhabditis elegans. We determined the in vivo functions of 25 of the 26 GABAergic neurons by killing these cells with a laser microbeam in living animals and by characterizing a mutant defective in GABA expression. On the basis of the ultrastructurally defined connectivity of the C. elegans nervous system, we deduced how these GABAergic neurons act to control the body and enteric muscles necessary for different behaviours. Our findings provide evidence that GABA functions as an excitatory as well as an inhibitory neurotransmitter.
γ-氨基丁酸（GABA）是脊椎动物和无脊椎动物中最丰富的抑制性神经递质。GABA受体是抗焦虑药、抗癫痫药和抗痉挛药以及常用杀虫剂的作用靶点。像GABA这样的特定神经递质是如何控制动物行为的呢？为了回答这个问题，我们在秀丽隐杆线虫的神经系统中鉴定出了所有能与针对神经递质GABA产生的抗血清发生反应的神经元。我们通过用激光微束在活体动物中杀死这些细胞，并通过对GABA表达缺陷的突变体进行表征，确定了26个GABA能神经元中25个的体内功能。基于秀丽隐杆线虫神经系统超微结构定义的连接性，我们推断出这些GABA能神经元是如何发挥作用来控制不同行为所需的身体和肠道肌肉的。我们的研究结果提供了证据，表明GABA既作为兴奋性神经递质，也作为抑制性神经递质发挥作用。
