Project ID NS-MH2023_12


Co Supervisor 1A IoPPN/Wolfson CARDWebsite

Co Supervisor 1B FoLSM/Women and Children’s Health, SoLCSWebsite

The amygdala, a key upstream regulator of the hypothalamic GnRH pulse generator

The amygdala, a key limbic brain structure commonly known for its role in higher-order emotional processing, is implicated in stress-induced suppression of gonadotrophin-releasing hormone (GnRH) pulse generator frequency, to cause infertility. Our pioneering discovery that kisspeptin signalling in the medial amygdala robustly regulates hypothalamic GnRH pulse generator frequency, provides new insight into how the amygdala controls reproduction. The medial amygdala comprises primarily GABAergic neurones with a predominantly (60%) inhibitory GABA output to the hypothalamus. The medial amygdala is also rich in the stress neuropeptide urocortin-3, which is activated by psychological stress. We hypothesise that the urocortin system regulates kisspeptin-GABAergic signalling intrinsic to the medial amygdala to mediate the effects of psychological stress on fertility in the female mouse.


To establish the functional dynamic relationship between the kisspeptin and GABA neurocircuitry in the medial amygdala that underlie the upstream regulation of the hypothalamic GnRH pulse generator frequency using in-vivo optogenetics and deep-brain GCaMP6 GRIN lens microendoscopic calcium imaging.

To determine how the GABAergic projections from the medial amygdala modulate the frequency of the hypothalamic GnRH pulse generator.

To determine how stress activated urocortin-3 neurones regulate kisspeptin-GABA neurocircuitry in the medial amygdala to suppress GnRH pulse generator frequency.

Professors O’Byrne and Cox have worked together for many years, with vast experience in complex in-vivo experimentation. This project will use the latest cutting-edge technologies of combined targeted optogenetic manipulations with in-vivo gradient-index (GRIN) lens microendoscopic systems to monitor in real time neurone calcium dynamics, a proxy for neuronal activity, of selective GCaMP-expressing neurones.

One representative publication from each co-supervisor:

Voliotis M, Feng Li X, De Burgh R, Lass G, Lightman SL, O’Byrne KT, Tsaneva-Atanasova K. The origin of GnRH pulse generation: An integrative mathematical-experimental approach. J Neurosci. 2019, 9:9738-9747. doi: 10.1523/JNEUROSCI.0828-19.2019.

M Ghamari-Langroudi, GJ Digby, JA Sebag, GL Millhauser, R Palomino, R Matthews, T Gillyard, IR Tough, HM Cox, JS Denton & RD Cone. G-protein-independent coupling of MC4R to Kir7.1 in hypothalamic neurons. Nature 2015, 520:94-98 doi: 10.1038/nature14051