Effects of gamma-aminobutyric acid(A) receptor manipulation on migrating gonadotropin-releasing hormone neurons through the entire migratory route invivo and in vitro

GnRH neurons originate in the nasal compartment and migrate along vomeronas al fibers over the cribiform plate to the forebrain. Previously, we found g amma-aminobutyric acid (GABA) present in GnRH neurons during development. T o clarify the influence of GABA across the entire GnRH migration route, we examined the effects of muscimol and bicuculline (GABA(A) agonist and antag onist) in vivo and in vitro, maintaining the integrity of the nasal-forebra in connection. For in vivo experiments, mice were administered muscimol, bi cuculline, or vehicle on days 10-15 of pregnancy and were killed on embryon ic day 15 (E15). For in vitro experiments, 250-mu m parasagittal slices of whole heads of E13 mice were incubated with muscimol, bicuculline, or vehic le for 2 days. Muscimol inhibited GnRH cell migration and decreased extensi on of GnRH fibers. Bicuculline treatment led to a disorganized distribution of GnRH cells in the forebrain and a concomitant dissociation of GnRH cell s from fibers of guidance. These results suggest that GABA's influence on G nRH development changes as the cells move out of the nasal compartment and extend processes toward the median eminence.