Differential response of cortical plate and ventricular zone cells to GABA as a migration stimulus.
A microdissection technique was used to separate differentiated cortical plate (cp) cells from immature ventricular zone cells (vz) in the rat embryonic cortex. The cp population contained >85% neurons (TUJ1(+)), whereas the vz population contained approximately 60% precursors (nestin+ only). The chemotropic response of each population was analyzed in vitro, using an established microchemotaxis assay. Micromolar GABA (1-5 microM) stimulated the motility of cp neurons expressing glutamic acid decarboxylase (GAD), the rate-limiting enzyme in GABA synthesis. In contrast, femtomolar GABA (500 fM) directed a subset of GAD- vz neurons to migrate. Thus, the two GABA concentrations evoked the motility of phenotypically distinct populations derived from different anatomical regions. Pertussis toxin (PTX) blocked GABA-induced migration, indicating that chemotropic signals involve G-protein activation. Depolarization by micromolar muscimol, elevated [K+]o, or micromolar glutamate arrested migration to GABA or GABA mimetics, indicating that migration is inhibited in the presence of excitatory stimuli. These results suggest that GABA, a single ligand, can promote motility via G-protein activation and arrest attractant-induced migration via GABAA receptor-mediated depolarization.
Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
T N
TN
Behar
A E
AE
Schaffner
C A
CA
Scott
C
C
O'Connell
J L
JL
Barker
D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology*; D002552:Cerebral Ventricles / Q000166:cytology / Q000196:embryology*; D002630:Chemotactic Factors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000502:physiology; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000502:physiology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009994:Osmolar Concentration; D037342:Pertussis Toxin; D051381:Rats / Q000196:embryology; D017207:Rats, Sprague-Dawley; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D002630:Chemotactic Factors; D010566:Virulence Factors, Bordetella; D005680:gamma-Aminobutyric Acid; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D005968:Glutamate Decarboxylase