Reproduction in vertebrates is governed by gonadotropin-releasing hormone (GnRH) neurons, which release GnRH at the median eminence (ME) to stimulate the secretion of the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary gland. Gonadotropins in turn act in the gonads to promote gametogenesis and steroidogenesis. In males and females, LH secretion occurs in pulses, driven by episodic GnRH release at the ME. In females, a surge in LH secretion, stimulated in most species by an outpour of GnRH, triggers ovulation. In spontaneously ovulating species, estrogen and progesterone secretion finely tune GnRH and gonadotropin release across the ovulatory cycle through feedback regulation, in combination with internal and environmental cues.

Two reports that familial inactivating mutations of the GPR54 gene – encoding the G protein-coupled receptor GPR54 (now referred to as KISS1R) that binds the kisspeptin (KISS1) peptides – cause hypogonadotropic hypogonadism (de Roux et al., 2003, Seminara et al., 2003) propelled kisspeptin-KISS1R signaling to center stage in the regulation of the hypothalamic-pituitary-gonadal (HPG) axis. Identification, shortly thereafter, of Kiss1-expressing neurons in gonadal steroid hormone-sensitive hypothalamic nuclei (Gottsch et al., 2004) prompted a flurry of research into their roles in generating the specific patterns of GnRH and LH secretion, and in relaying gonadal steroid hormone feedback and internal and environmental cues to GnRH neurons [reviewed in (Herbison, 2015)]. In the past ten years, a large body of work, carried out almost exclusively in rodents, and employing modern functional approaches such as patch-clamp electrophysiology, calcium imaging, computer modelling, and chemo- and optogenetics, has substantially contributed to expanding our knowledge of kisspeptin regulation of GnRH neurons.

The purpose of this review is to integrate available information to provide the reader with a comprehensive and up-to-date overview of kisspeptin neuron neurophysiology. We will discuss the intrinsic electrophysiological properties of these cells, their place in neuronal circuits that regulate GnRH neuron activity and other functions, and, importantly, regulation of their electrophysiological characteristics by gonadal steroid feedback. Before diving into the details of kisspeptin neuron electrophysiology, we will first give a brief primer on these cells and their roles, discuss the animal models that have been used to study their neurophysiology and provide an account of the various recording configurations that have been employed.