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The Journal of Neuroscience, April 1, 1998, 18(7):2560-2569
GABA Inhibits Migration of Luteinizing Hormone-Releasing Hormone
Neurons in Embryonic Olfactory Explants
Susan M.
Fueshko,
Sharon
Key, and
Susan
Wray
Laboratory of Neurochemistry, National Institute of Neurological
Diseases and Stroke, National Institutes of Health, Bethesda, Maryland
20892-4130
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.
Key words:
GABA; GnRH; olfactory; peripherin; tetrodotoxin; immunocytochemistry
Copyright © 1998 Society for Neuroscience 0270-6474/98/1872560-10$05.00/0
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