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GnRH pulse generator frequency is modulated by kisspeptin and GABA-glutamate interactions in the posterodorsal medial amygdala in female mice

By Geffen Lass, Xiaofeng Li, Ross Alexander de Burgh, Deyana Ivanova, Caitlin McIntyre, Xian-Hua Lin, William H Colledge, Stafford Lightman, Kevin O'Byrne

Posted 27 Nov 2021
bioRxiv DOI: 10.1101/2021.11.27.470131

Kisspeptin neurons in the arcuate nucleus of the hypothalamus generate GnRH pulses, and act as critical initiators of functional gonadotrophin secretion, and reproductive competency. However, kisspeptin in other brain regions, most notably the posterodorsal subnucleus of the medial amygdala (MePD), plays a significant modulatory role over the hypothalamic kisspeptin population; our recent studies using optogenetics have shown that low frequency light stimulation of MePD kisspeptin results in increased LH pulse frequency. Nonetheless, the neurochemical pathways that underpin this regulatory function remain unknown. To study this, we have utilised an optofluid technology, precisely combining optogenetic stimulation with pharmacological receptor antagonism, to investigate the neurotransmission involved in this circuitry. We have shown that functional neurotransmission of both GABAA and glutamate is a requirement for effective modulation of the GnRH pulse generator by amygdala kisspeptin neurons.

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