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Allan Herbison Project

Supervisor:   Allan Herbison

 

Brainstem inputs to the GnRH pulse generator controlling fertility

A wide range of environmental and internal homeostatic factors modulate the reproductive hormone secretion and fertility of an individual (Herbison, 2016).  After more than three decades of searching, the neurons responsible for generating pulsatile hormone secretion have been identified as the kisspeptin neurons located in the arcade nucleus of the hypothalamus (Clarkson et al., 2017).  The serotonin and noradrenaline neurons of the brainstem project to multiple forebrain neuronal networks to modulate fundamental aspects of life including stress, mood and arousal state. This project aims to examine the impact of brainstem noradrenaline and serotonin neurons on the kisspeptin pulse generator, reproductive hormone secretion, and fertility in genetically-modified mice. The project will use cutting-edge neuroscience approaches including viral tract tracing and super-resolution imaging to initially examine the connections between brainstem neurons and kisspeptin cells and, subsequently, real-time GCaMP calcium imaging and opto/chemogenetic approaches (Han et al., 2018) to observe and manipulate the activity of brainstem inputs to kisspeptin neurons in conscious mice. These studies are aimed at understanding the core neural network responsible for controlling reproductive hormone secretion with a view to improving the treatment of infertility in the clinic.

Relevant references:

1.  Herbison AE (2016) Control of puberty onset and fertility by gonadotropin-releasing hormone neurons. Nature Rev Endo, 12, 452-466. 

2.  Clarkson J, Han SY, Piet R, McLennan T, Kane G, Ng J, Porteous R, Kim J, Colledge WH, Iremonger KJ, Herbison AE (2017) Definition of the hypothalamic GnRH pulse generator in mice. Proc Natl Acad Sci (USA) 114, E10216-E10223.

3.  Han SY, Clarkson J, Piet R, Herbison AE (2018) Optical approaches for interrogating neural circuits controlling hormone secretion. Endocrinology, 159, 3822-3833.