Research
We are focused upon understanding the properties and functioning of the key neural populations controlling fertility in mammals; the gonadotropin-releasing hormone (GnRH) neurons and the kisspeptin neurons. Together, these cells generate the “pulse” and “surge” patterns of hormone secretion that are responsible for the initiation of puberty and the subsequent maintenance of reproductive function in adult males and females.
Our key questions are -
- How does this neural circuitry produce the abrupt episodes of GnRH secretion that generate pules of reproductive hormone secretion?
- How can this same circuitry generate a completely different “surge” pattern of GnRH secretion at the mid-point of the female cycle to trigger ovulation?
- How do steroids such as estrogen and progesterone modulate this neural circuitry?
- What goes wrong in this neural circuitry in conditions of infertility such as polycystic ovary syndrome (PCOS)?
Studies are undertaken in a variety of genetically-modified mouse models using tissue clearing and expansion microscopy, single cell electrophysiology and calcium imaging in acute brain slices in vitro, RNAseq gene profiling, in vivo imaging of the activity of selected neurons and neural populations in freely-behaving mice, and in vivo CRISPR-based gene editing.
Funding
BBSRC
Francis Ortiz Garcia (Senior Research Technician)
Paul Morris (Postdoctoral Fellow)
Szilvia Vas (Postdoctoral Fellow)
Miguel Ruiz Cruz (Postdoctoral Fellow)
Publications
Vas S, Morris PG, Gul Z, Ruiz-Cruz M, Han SY, Herbison AE (2025) Brainstem noradrenergic control of the kisspeptin neuron GnRH pulse generator. Nature Communications 16, 5772. https://doi.org/10.1038/s41467-025-60837-8
Han SY, Yeo SH, Kim JC, Zhou Z, Herbison AE (2025) Multi-dimensional oscillatory activity patterns of GnRH neurons in vivo. eLife 13, doi: 10.7554/eLife.100856
Zhou Z, Han SY, Pardo-Navarro M, Wall EG, Desai R, Vas S, Handelsman DJ, Herbison AE (2025) GnRH pulse generator activity in mouse models of polycystic ovary syndrome. eLife 13, doi: 10.7554/eLife.97179
Han SY, Morris PG, Kim JC, Guru S, Pardo-Navarro M, Yeo S-H, McQuillan HJ, Herbison AE (2023) Mechanism of kisspeptin neuron synchronization for pulsatile hormone secretion in male mice. Cell Reports 42, 111914.doi.org/10.1016/j.celrep.2022.111914
Clarkson J, Yip SH, Porteous R, Kauff A, Heather AK, Herbison AE (2023) CRISPR-Cas9 knockdown of ESR1 in preoptic GABA-kisspeptin neurons abolishes the preovulatory surge and estrous cycles in female mice. eLife 12 doi.org/10.7554/eLife.90959.3
McQuillan HJ, Clarkson J, Kauff A, Han SY, Yip SH, Cheong I, Porteous P, Heather AK, Herbison AE (2022) Definition of the estrogen negative feedback pathway controlling the GnRH pulse generator in female mice. Nature Communications13, 7433. doi.org/10.1038/s41467-022-35243-z
Liu X, Yeo SH, McQuillan HJ, Herde MK, Hessler S, Cheong I, Porteous R, Herbison AE (2021) Highly redundant neuropeptide volume co-transmission underlying episodic activation of the GnRH neuron dendron. eLife 10, e62455 doi: 10.7554/eLife.62455
Wang L, Guo WY, Shen X, Yeo SH, Long H, Wang ZX, Lyu QF, Herbison AE, Kuang YP (2020) Different dendritic domains of the GnRH neuron underlie the pulse and surge modes of GnRH secretion in female mice. eLife 9, e53945doi: 10.7554/eLife.53945
Clarkson, J., Han, S. Y., Piet, R., McLennan, T., Kane, G. M., Ng, J., Porteous, R., … Herbison, A. E. (2017). Definition of the hypothalamic GnRH pulse generator in mice. Proceedings of the National Academy of Sciences, 114(47), E10216-E10223. doi: 10.1073/pnas.1713897114
