Mechanism of kisspeptin neuron synchronization for pulsatile hormone secretion in male mice

Abstract

The mechanism by which arcuate nucleus kisspeptin (ARN^KISS) neurons co-expressing glutamate, neurokinin B, and dynorphin intermittently synchronize their activity to generate pulsatile hormone secretion remains unknown. An acute brain slice preparation maintaining synchronized ARN^KISS neuron burst firing was used alongside in vivo GCaMP GRIN lens microendoscope and fiber photometry imaging coupled with intra-ARN microinfusion. Studies in intact and gonadectomized male mice revealed that ARN^KISS neuron synchronizations result from near-random emergent network activity within the population and that this was critically dependent on local glutamate-AMPA signaling. Whereas neurokinin B operated to potentiate glutamate-generated synchronizations, dynorphin-kappa opioid tone within the network served as a gate for synchronization initiation. These observations force a departure from the existing "KNDy hypothesis" for ARN^KISS neuron synchronization. A "glutamate two-transition" mechanism is proposed to underlie synchronizations in this key hypothalamic central pattern generator driving mammalian fertility.

Keywords: CP: Neuroscience; GnRH; arcuate nucleus; dynorphin; glutamate; kisspeptin; luteinizing hormone; neurokinin B; pattern generator; pulsatility; synchronization.