The proper functioning of gonadotropin releasing hormone (GnRH) neurons is necessary for the reproductive success of an organism. During development, the migratory route of GnRH neurons proceeds from their peripheral birthplace in the olfactory placode, across the cribriform plate and to their final destination in the basal forebrain (BF). These neurons migrate along olfactory fibers. The disruption of these fibers during development results in anosmia. and hypogonadism. The mechanisms that contribute to this relatively unique migration are largely unknown. Preliminary data suggest that the neurotransmitter gamma-aminobutyric acid (GABA) may play a role in regulating GnRH neuronal migration. We have developed a slice preparation which maintains the integrity of the GnRH migratory pathway. The current proposal focuses on 3 specific aspects of this GABA effect. First, the involvement of the three specific GABA receptors will be investigated through localization of these receptors along the migratory route by use of immunocytochemistry and through specific receptor activation in embryonic slices in vitro. Second, the role of Ca2+ in GABA-mediated GnRH neuronal migration will be investigated through the use of Ca2+ channel blockers and Ca2+ chelators in addition to GABAergic drugs in vitro. Third, the presence of GABA in a subpopulation of GnRH neurons will be investigated in two ways. First, the process by which GABA is found in these GnRH neurons will be explored by immunocytochemistry for the synthesizing enzymes glutamic acid decarboxylase (GAD 65 and GAD 67) or aldehyde dehydrogenase (AD) and the GABA transporter, GAT-1. Second, the role of GABA in GnRH neurons in GABA-mediated GnRH neuronal migration will be studied through the use of GAD and AD inhibitors, and GAT blockers in addition to GABAergic drugs in vitro.
|Bless, E P; Westaway, W A; Schwarting, G A et al. (2000) Effects of gamma-aminobutyric acid(A) receptor manipulation on migrating gonadotropin-releasing hormone neurons through the entire migratory route in vivo and in vitro. Endocrinology 141:1254-62|