GABA inhibits migration of luteinizing hormone-releasing hormone neurons in embryonic olfactory explants

During development, a subpopulation of olfactory neurons transiently expresses GABA. The spatiotemporal pattern of GABAergic expression coincides with migration of luteinizing hormone-releasing hormone (LHRH) neurons from the olfactory pit to the CNS. In this investigation, we evaluated the role of GABAergic input on LHRH neuronal migration using olfactory explants, previously shown to exhibit outgrowth of olfactory axons, migration of LHRH neurons in association with a subset of these axons, and the presence of the olfactory-derived GABAergic neuronal population. GABAA receptor antagonists bicuculline (10(-5) M) or picrotoxin (10(-4) M) had no effect on the length of peripherin-immunoreactive olfactory fibers or LHRH cell number. However, LHRH cell migration, as determined by the distance immunopositive cells migrated from olfactory pits, was significantly increased by these perturbations. Addition of tetrodotoxin (10(-6) M), to inhibit Na+-transduced electrical activity, also significantly enhanced LHRH migration. The most robust effect observed was dramatic inhibition of LHRH cell migration in explants cultured in the presence of the GABAA receptor agonist muscimol (10(-4) M). This study demonstrates that GABAergic activity in nasal regions can have profound effects on migration of LHRH neurons and suggests that GABA participates in appropriate timing of LHRH neuronal migration into the developing brain.