Endocrinol Metab.  2016 Jun;31(2):193-205. 10.3803/EnM.2016.31.2.193.

Kisspeptin Regulation of Neuronal Activity throughout the Central Nervous System

• Liu X
• Herbison A

• KMID: 2308848
• DOI: http://doi.org/10.3803/EnM.2016.31.2.193

Abstract

Kisspeptin signaling at the gonadotropin-releasing hormone (GnRH) neuron is now relatively well characterized and established as being critical for the neural control of fertility. However, kisspeptin fibers and the kisspeptin receptor (KISS1R) are detected throughout the brain suggesting that kisspeptin is involved in regulating the activity of multiple neuronal circuits. We provide here a review of kisspeptin actions on neuronal populations throughout the brain including the magnocellular oxytocin and vasopressin neurons, and cells within the arcuate nucleus, hippocampus, and amygdala. The actions of kisspeptin in these brain regions are compared to its effects upon GnRH neurons. Two major themes arise from this analysis. First, it is apparent that kisspeptin signaling through KISS1R at the GnRH neuron is a unique, extremely potent form or neurotransmission whereas kisspeptin actions through KISS1R in other brain regions exhibit neuromodulatory actions typical of other neuropeptides. Second, it is becoming increasingly likely that kisspeptin acts as a neuromodulator not only through KISS1R but also through other RFamide receptors such as the neuropeptide FF receptors (NPFFRs). We suggest likely locations of kisspeptin signaling through NPFFRs but note that only limited tools are presently available for examining kisspeptin cross-signaling within the RFamide family of neuropeptides.

Keyword

Gonadotropin-releasing hormone; Kisspeptin; KISS1R; NPFF; Neuropeptide FF receptor; Amygdala; Hippocampus; Oxytocin; Vasopressin; Arcuate nucleus; Dopamine

MeSH Terms

Amygdala
Arcuate Nucleus of Hypothalamus
Brain
Central Nervous System*
Dopamine
Fertility
Gonadotropin-Releasing Hormone
Hippocampus
Humans
Neurons*
Neuropeptides
Neurotransmitter Agents
Oxytocin
Synaptic Transmission
Vasopressins
Dopamine
Gonadotropin-Releasing Hormone
Neuropeptides
Neurotransmitter Agents
Oxytocin
Vasopressins

Figure

• 

  Fig. 1 Kisspeptin 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. 2 Schematic 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.

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