Optogenetic stimulation of kisspeptin neurones within the posterodorsal medial amygdala increases LH pulse frequency in female mice

<p>Kisspeptin within the arcuate nucleus of the hypothalamus is a critical neuropeptide in the regulation of reproduction. &nbsp;Together with neurokinin B and dynorphin A, arcuate kisspeptin provides the oscillatory activity that drives the pulsatile secretion of GnRH, and therefore LH pulses, and is believed to be a central component of the GnRH pulse generator. &nbsp;It is well established that the amygdala also exerts an influence over gonadotrophic hormone secretion and reproductive physiology. &nbsp;The discovery of kisspeptin and its receptor within the posterodorsal medial amygdala (MePD), and our recent finding showing that intra-MePD administration of kisspeptin or a kisspeptin receptor antagonist results in increased LH secretion and decreased LH pulse frequency, respectively, suggests an important role for amygdala kisspeptin signalling in the regulation of the GnRH pulse generator. &nbsp;To further investigate the function of amygdala kisspeptin, the present study used an optogenetic approach to selectively stimulate MePD kisspeptin neurones and examine the effect on pulsatile LH secretion. &nbsp;MePD kisspeptin neurones in conscious Kiss1-Cre mice were virally infected to express the channelrhodopsin 2 protein and selectively stimulated by light via a chronically implanted fibre optic cannula. &nbsp;Continuous stimulation using 5 Hz resulted in an increased LH pulse frequency, which was not observed at the lower stimulation frequencies of 0.5 and 2 Hz. &nbsp;In wild-type animals, continuous stimulation at 5 Hz did not affect LH pulse frequency. &nbsp;These results demonstrate that selective activation of MePD <em>Kiss1</em> neurons can modulate hypothalamic GnRH pulse generator frequency.</p>