In situ GABAergic modulation of synchronous gonadotropin releasing hormone-1 neuronal activity

Evidence indicates that gonadotropin releasing hormone-1 [GnRH-1, also known as luteinizing hormone releasing hormone (LHRH)] neurons can exhibit synchronized neuroendocrine secretory activity before entrance into the CNS. In this study, we used calcium imaging to evaluate patterns of activity in individual, embryonic, GnRH-1 neurons as well as population dynamics of GnRH-1 neurons in mouse nasal explants maintained for 1 versus 3 weeks. Independent of age, GnRH-1 neurons displayed significant calcium peaks that synchronized at an interval of approximately 20 min across multiple GnRH-1 cells within an explant. Acute tetrodotoxin treatment decreased the amplitude of calcium peaks in individual GnRH-1 neurons and the duration but not the frequency of synchronized activity in the population of GnRH-1 neurons. Acute GABA(B) receptor antagonism increased the frequency of synchronized neuronal activity at both ages, whereas acute GABA(A) receptor antagonism decreased calcium oscillations in individual GNRH-1 cells as well as synchronization of the calcium pulses within the GnRH-1 population at the 1 week time point to background non-GNRH-1 cell levels. These results indicate that developing GnRH-1 neurons rely heavily on GABAergic signaling to initiate synchronized bouts of activity but thereafter, possess an innate capacity for synchronized activity patterns that are modulated by, but not completely dependent on GABAergic signaling.