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
Wellcome Trust
Shel Hwa Yeo (Postdoctoral Fellow)
Publications
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, e53945 doi: 10.7554/eLife.53945
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
Herbison AE (2018) The gonadotropin-releasing hormone pulse generator. Endocrinology, 159, 3723-3736. doi:10:1210/en.2018-00653
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
Herbison, A. E. (2016). Control of puberty onset and fertility by gonadotropin-releasing hormone neurons. Nature Reviews Endocrinology, 12, 452-466. doi: 10.1038/nrendo.2016.70
Han, S. Y., McLennan, T., Czieselsky, K., & Herbison, A. E. (2015). Selective optogenetic activation of arcuate kisspeptin neurons generates pulsatile luteinizing hormone secretion. Proceedings of the National Academy of Sciences, 112(42), 13109-13114. doi: 10.1073/pnas.1512243112
Campos, P., & Herbison, A. E. (2014). Optogenetic activation of GnRH neurons reveals minimal requirements for pulsatile luteinizing hormone secretion. Proceedings of the National Academy of Sciences, 111(51), 18387-18392. doi: 10.1073/pnas.1415226112
Kirilov, M., Clarkson, J., Liu, X., Roa, J., Campos, P., Porteous, R., … Herbison, A. E. (2013). Dependence of fertility on kisspeptin—Gpr54 signalling at the GnRH neuron. Nature Communications, 4, 2492. doi: 10.1038/ncomms3492
