Abstract
The mechanism by which arcuate nucleus kisspeptin (ARNKISS) 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 ARNKISS 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 ARNKISS 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 ARNKISS neuron synchronization. A “glutamate two-transition” mechanism is proposed to underlie synchronizations in this key hypothalamic central pattern generator driving mammalian fertility.
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•Arcuate kisspeptin neurons synchronize their activity in a non-linear manner•Glutamate-AMPA signaling is critical for kisspeptin neuron synchronizations•Neurokinin B transmission potentiates glutamate-driven synchronizations•Dynorphin exerts state-dependent control of synchronization initiation
Hypothalamic kisspeptin neurons comprise the central pattern generator driving pulsatile reproductive hormone secretion in mammals. Han et al. show that the great majority of kisspeptin neurons exhibit brief periods of synchronized activity that are driven by glutamate transmission and modulated by the neuropeptides dynorphin and neurokinin B.