Expression of gamma-aminobutyric acid and gonadotropin-releasing hormone during neuronal migration through the olfactory system.

ABSTRACT

Neurons containing the decapeptide GnRH originate in the olfactory placodes and migrate into the central nervous system during fetal development. The neurotransmitter gamma-aminobutyric acid (GABA) has been proposed as a trophic factor and may also influence neuronal migration. Immunocytochemical analyses were conducted in fetal rats, mice, and humans to identify potential developmental relationships between cells containing GABA, and GnRH neurons. Cells containing GABA were found along the nasal portion of the GnRH migration pathway in rats, mice, and humans during development. A peak number of cells containing immunoreactive GABA was observed in the nasal compartment of rats at embryonic day 15. At this time (E15), a majority of GnRH neurons were clustered in the region of the cribriform plate. By postnatal day 1, all GnRH neurons had migrated into the CNS and GABA cells were virtually absent from the nasal compartment. Double-label and confocal analyses of GABA and GnRH in mice and rats demonstrated that some olfactory GABAergic neurons coexpress GnRH. This implies that neurons that transiently express GABA originate in olfactory placodes and migrate into the forebrain. Based on the transient dual-label and adjacent relationships between GABA and GnRH containing cells in the nasal compartment, and other data showing migrational and trophic roles for GABA in development, we suggest that GABA may directly influence GnRH neuronal migration and development.