Effects of γ-aminobutyric acidA receptor manipulation on migrating gonadotropin-releasing hormone neurons through the entire migratory route in vivo and in vitro

GnRH neurons originate in the nasal compartment and migrate along vomeronasal fibers over the cribiform plate to the forebrain. Previously, we found gamma-aminobutyric acid (GABA) present in GnRH neurons during development. To clarify the influence of GABA across the entire GnRH migration route, we examined the effects of muscimol and bicuculline (GABA(A) agonist and antagonist) in vivo and in vitro, maintaining the integrity of the nasal-forebrain connection. For in vivo experiments, mice were administered muscimol, bicuculline, or vehicle on days 10-15 of pregnancy and were killed on embryonic day 15 (E15). For in vitro experiments, 250-mu m parasagittal slices of whole heads of E13 mice were incubated with muscimol, bicuculline, or vehicle for 2 days. Muscimol inhibited GnRH cell migration and decreased extension of GnRH fibers. Bicuculline treatment led to a disorganized distribution of GnRH cells in the forebrain and a concomitant dissociation of GnRH cells from fibers of guidance. These results suggest that GABA's influence on GnRH development changes as the cells move out of the nasal compartment and extend processes toward the median eminence.