Control of firing by small ( S)-α-amino-3-hydroxy-5-methyl-isoxazolepropionic acid-like inputs in hypothalamic gonadotropin releasing-hormone (GnRH) neurons

Abstract

Episodic release of gonadotropin releasing hormone (GnRH) is obligatory for mammalian reproduction. The contribution of synaptic input to intermittent firing of GnRH neurons is unclear. GnRH neurons have very few synapses and most post-synaptic currents are small. Therefore, the impact of synaptic currents on firing in GnRH neurons was directly examined using simulated ( S)-α-amino-3-hydroxy-5-methyl-isoxazolepropionic acid (AMPA)-like inputs applied with the method of dynamic current clamping. Tightly synchronized inputs and 50 ms bursts of excitatory input resulted in action potentials that were coincident with the stimulus. Neither input pattern resulted in sustained firing. When ongoing patterns of simulated inputs were applied over a range of parameters, action potentials were associated with clusters of AMPA-like inputs of 250 pS (approximately 15 pA amplitudes), while single inputs of 500 pS (approximately 30 pA amplitudes) resulted in action potentials. Ongoing inputs of 500 pS drove firing at 4–9 Hz. These findings provide evidence that small, simulated glutamatergic inputs can control firing in GnRH neurons and suggest that despite the small amplitudes, endogenous synaptic input mediated by glutamate may contribute to firing in GnRH neurons.