Pacemaking kisspeptin neurons

Kisspeptin (Kiss1) neurons are vital for reproduction. Gonatotrophin-releasing hormone (GnRH) neurons express the kisspeptin receptor (GPR54), and kisspeptins potently stimulate the release of GnRH by depolarizing and inducing sustained action potential firing in GnRH neurons. As such, Kiss1 neurons may be the presynaptic pacemaker neurons in the hypothalamic circuitry that controls reproduction. There are at least two different populations of Kiss1 neurons; one in the rostral periventricular area (RP3V) that is stimulated by oestrogens and the other in the arcuate nucleus that is inhibited by oestrogens. How each of these Kiss1 neuronal populations participates in the regulation of the reproductive cycle is currently under intense investigation. Based on electrophysiological studies in the guinea-pig and mouse, Kiss1 neurons in general are capable of generating burst-firing behaviour. Essentially, all Kiss1 neurons, which have been studied thus far in the arcuate nucleus, express the ion channels necessary for burst firing, which include hyperpolarization-activated, cyclic nucleotide-gated cation (HCN) channels and the T-type calcium (Cav3.1) channels. In voltage-clamp conditions, these channels produce distinct currents that can generate burst-firing behaviour in current-clamp conditions. The future challenge is to identify other key channels and synaptic inputs involved in the regulation of the firing properties of Kiss1 neurons and the physiological regulation of the expression of these channels and receptors by oestrogens and other hormones. The ultimate goal is to understand how Kiss1 neurons control the different phases of GnRH neurosecretion, hence reproduction.