Fig. 1Kisspeptin actions on the excitability of different central nervous system (CNS) neurons. (A) Voltage recording of gonadotropin-releasing hormone (GnRH) neuron action potential firing from a female green fluorescent protein-GnRH mouse showing the typical long-lasting excitation evoked by a short 2-minute (grey bar) application of 10 nM kisspeptin. (B) Ratemeter histograms of action potential firing in two oxytocin neurons from a urethane-anaesthetized day 18 pregnant rat showing the effects of intracerebroventricular injection (ICV) and intravenous injection (IV) of kisspeptin, respectively (recordings kindly provided by Drs V. Scott, A.J. Seymour, and C.H. Brown, University of Otago, Dunedin, New Zealand). (C) Voltage recording of ARC neuron action potential firing from a Kiss1r-null female mouse showing short-lasting excitatory responses to 400 nM kisspeptin and RFRP-3. Adapted from Liu et al. [20], with permission from Endocrine Society. (D) Whole cell current recordings from hippocampal dentate granule neurons in rats showing that 600 nM kisspeptin increases the amplitude of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated excitatory postsynaptic currents (EPSC). Left, histogram of mean response. Right, example of EPSCs during control and after 600 nM kisspeptin (recordings kindly provided by Prof. Amy Arai, Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL, USA).
Fig. 2Schematic diagram showing possible signaling pathways for kisspeptin in the central nervous system (CNS). The distinction is made between signaling through kisspeptin receptor (KISS1R), neuropeptide FF receptor (NPFFR) and possibly even other RFamide receptors. Signaling through KISS1R may be either an essential synaptic driver (gonadotropin-releasing hormone [GnRH] neurons) or neuromodulatory (proposed for other CNS neurons), whereas signaling through NPFFRs is suggested to be neuromodulatory throughout the CNS. The primary ion channels modulated by kisspeptin are noted for each mode of signaling. NSCC, non-selective cation ion channels; POMC, pro-opiomelanocortin; NCX, sodium-calcium exchanger; AMPA, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid.