Brainstem noradrenergic modulation of the kisspeptin neuron GnRH pulse generator in mice

Szilvia Vas, Paul G. Morris, Zulfiye Gul, Miguel Ruiz-Cruz, Su Young Han and Allan E. Herbison ()
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Szilvia Vas: University of Cambridge
Paul G. Morris: University of Cambridge
Zulfiye Gul: University of Cambridge
Miguel Ruiz-Cruz: University of Cambridge
Su Young Han: University of Cambridge
Allan E. Herbison: University of Cambridge

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract Brainstem noradrenaline (NA) neurons modulate the activity of many neural networks including those responsible for the control of fertility. Using brain slice electrophysiology, we demonstrate that the arcuate nucleus kisspeptin (ARNKISS) neurons, recently identified to be the gonadotropin-releasing hormone (GnRH) pulse generator, are directly hyperpolarized by NA through both alpha 2- and beta-adrenergic receptors. Retrograde viral tracing shows that NA innervation of the ARN is primarily from the dorsal subdivision of the locus coeruleus (LC)-NA cell group and is substantially greater in females compared to males. Using an intersectional genetic approach allowing selective chemogenetic manipulation of NA neurons innervating the ARN alongside photometry recording of ARNKISS neuron synchronization behavior, we find that the activation of NA inputs strongly suppresses GnRH pulse generator activity in a sexually differentiated and gonadal steroid-dependent manner. Together these studies demonstrate a direct mechanism through which heightened activity in brainstem NA neurons can pause pulsatile reproductive hormone secretion.

Date: 2025
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DOI: 10.1038/s41467-025-60837-8

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