GABA-INDUCED MOTILITY OF SPINAL NEUROBLASTS DEVELOPS ALONG A VENTRODORSAL GRADIENT AND CAN BE MIMICKED BY AGONISTS OF GABA(A) AND GABA(B) RECEPTORS

During embryogenesis, neuroblasts proliferate within germinal zones, t hen migrate to their final positions, Although many neurons migrate al ong radial glial fibers, evidence suggests that environmental factors, as yet unidentified, also influence neuroblast movement. In vivo, ner ve growth factor (NGF) and gamma-aminobutyric acid (GABA) colocalize n ear target destinations of migratory neuroblasts, In vitro, embryonic spinal neurons migrate towards NGF and GABA (Behar et al.: J Neurosci 14:29-38, 1994), implying that the molecules may act as chemoattractan ts in vivo, Here, we have used an in vitro assay of migration to show that migratory responses to these attractants develop along a ventrodo rsal gradient that parallels terminal mitosis during cord development, and that GABA stimulates chemokinesis (motility without a gradient) v ia heterogeneous receptors involving separate signalling pathways, Bot h GABA(A) (muscimol) and GABA(B) (baclofen) agonists mimicked the effe cts of GABA in stimulating chemokinesis, Muscimol-induced motility was only blocked by GABA(A) antagonists (bicuculline or picrotoxin), wher eas migration to baclofen was blocked by antagonists of both GABA(A) a nd GABA(B) (2-hydroxysaclofen) receptors, Migration to baclofen, but n ot muscimol, was abolished in the presence of 8-bromo cAMP or pertussi s toxin, indicating that the former, but not the latter, attractant ma y stimulate motility via Gi/Go GTP binding proteins, and that PKA may modulate migratory responses to baclofen, Migration to GABA was partia lly attenuated by each of the GABA receptor antagonists, These results lead us to conclude that the natural ligand stimulates neuroblast mot ility via heterogeneous receptors coupled to different signalling mech anisms. (C) 1995 Wiley-Liss, Inc.