Career opportunities
MRC DTP PhD Studentship, King's College London
Salary: Fully funded
Closing date: 13:00, 29 October 2024
Contact details: Prof Kevin O’Byrne (Kevin.obyrne@kcl.ac.uk) and Prof Helen Cox (helen.cox@kcl.ac.uk)
How to apply: kcl-mrcdtp.com/apply
More about the PhD: kcl-mrcdtp.com/project/the-amygdala-a-key-upstream-regulator-of-the-hypothalamic-gnrh-pulse-generator-2
About the PhD
Topic: The amygdala, a key upstream regulator of the hypothalamic GnRH pulse generator
(i) Scientific basis of project:
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.
(ii) Aims:
We hypothesise that the urocortin system regulates kisspeptin-GABAergic signalling intrinsic to the medial amygdala to mediate the effects of psychological stress on fertility.
(iii) Techniques and skills:
O’Byrne and Cox have worked together for many years and have a 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.
(iv) Objectives:
- 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.
Representative Publications
Voliotis M, Li XF, De Burgh R, Lass G, Lightman SL, O’Byrne KT, Tsaneva-Atanasova K. Mathematical modelling elucidates core mechanisms underpinning GnRH pulse generation. J Neuroscience. 2019; pii: 0828-19. doi: 10.1523/JNEUROSCI.0828-19.2019.
Voliotis M, Li XF, De Burgh RA, Lass G, Ivanova D, McIntyre C, O’Byrne KT, Tsaneva-Atanasova K. Modulation of pulsatile GnRH dynamics across the ovarian cycle via changes in the network excitability and basal activity of the arcuate kisspeptin network. Elife. 2021 Nov 17;10: e71252.
McIntyre C, Li XF, Ivanova D, Wang J, O’Byrne KT. Hypothalamic PVN CRH neurons signal through PVN GABA neurons to suppress GnRH pulse generator frequency in female mice. Endocrinology. 2023 May 29;164(6):bqad075. doi: 10.1210/endocr/bqad075.
C Evans*, K Howells, R Suzuki, AJH Brown & HM Cox (2023). Regional characterization of TRPV1 and TRPA1 signalling in the mouse colon. Eur J Pharmacol. 954, 175897
IR Tough, ML Lund, B Patel, TW Schwartz & HM Cox (2023). Paracrine relationship between incretin hormones and endogenous 5-HT in the small and large intestine. Neurogastroenterol Motil. 35(8), e14589. doi: 10.1111/nmo.14589
