GnRH neurons and episodic bursting activity

doi:10.1016/S1043-2760(02)00698-7

Trends in Endocrinology & Metabolism

Volume 13, Issue 10, 1 December 2002, Pages 409-410

https://doi.org/10.1016/S1043-2760(02)00698-7 Get rights and content

Abstract

Our understanding of the cellular mechanisms underlying bursting activity in mammalian GnRH neurons and how these mechanisms relate to pulsatile hormone release continue to grow. However, the wide variability of phasic bursting patterns of GnRH neurons still leaves some unanswered questions about how cellular models translate into pulsatile hormone release.

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Cited by (35)

MRNA expression of ion channels in GnRH neurons: Subtype-specific regulation by 17β-estradiol
2013, Molecular and Cellular Endocrinology
Burst firing of neurons optimizes neurotransmitter release. GnRH neurons exhibit burst firing activity and T-type calcium channels, which are vital for burst firing activity, are regulated by 17β-estradiol (E2) in GnRH neurons. To further elucidate ion channel expression and E2 regulation during positive and negative feedback on GnRH neurosecretion, we used single cell RT-PCR and real-time qPCR to quantify channel mRNA expression in GnRH neurons. GFP-GnRH neurons expressed numerous ion channels important for burst firing activity. E2-treatment sufficient to induce an LH surge increased mRNA expression of HCN1 channels, which underlie the pacemaker current, the calcium-permeable Ca_V1.3, Ca_V2.2, Ca_V2.3 channels, and TRPC4 channels, which mediate the kisspeptin excitatory response. E2 also decreased mRNA expression of SK3 channels underlying the medium AHP current. Therefore, E2 exerts fundamental changes in ion channel expression in GnRH neurons, to prime them to respond to incoming stimuli with increased excitability at the time of the surge.
Regulation of endogenous conductances in GnRH neurons by estrogens
2010, Brain Research
Citation Excerpt :
However, the diurnal signal that precisely activates this current is unknown. In addition, GnRH neurons express a time-dependent, hyperpolarization-activated, cation current (Ih or pacemaker current) that contributes to rhythmic firing (Lagrange et al., 1995; Kelly and Wagner, 2002; Zhang et al., 2007). Neuronal excitability is also determined by the afterhyperpolarization (AHP) that follows an action potential, and SK channels underlie a component of the median afterhyperpolarization (mAHP) K+ currents in CA1 pyramidal cells and other neurons (Bond et al., 2004).
17β-estradiol (E2) regulates the activity of the gonadotropin-releasing hormone (GnRH) neurons through both presynaptic and postsynaptic mechanisms, and this ovarian steroid hormone is essential for cyclical GnRH neuronal activity and secretion. E2 has significant actions to modulate the mRNA expression of numerous ion channels in GnRH neurons and/or to enhance (suppress) endogenous conductances (currents) including potassium (K_ATP, A-type) and calcium low voltage T-type and high voltage L-type currents. Also, it is well documented that E2 can alter the excitability of GnRH neurons via direct action, but the intracellular signaling cascades mediating these actions are not well understood. As an example, K_ATP channels are critical ion channels needed for maintaining GnRH neurons in a hyperpolarized state for recruiting T-type calcium channels that are important for burst firing in GnRH neurons. E2 modulates the activity of K_ATP channels via a membrane-initiated signaling pathway in GnRH neurons. Obviously there are other channels, including the small conductance activated K⁺ (SK) channels, that maybe modulated by this signaling pathway, but the ensemble of mER-, ERα-, and ERβ-mediated effects both pre- and post-synaptic will ultimately dictate the excitability of GnRH neurons.
Identified GnRH neuron electrophysiology: A decade of study
2010, Brain Research
Citation Excerpt :
Of interest, GnRH itself alters pacemaking of teleost terminal nerve GnRH neurons in part via altering calcium-activated potassium and calcium conductances (Abe and Oka, 2002). Ih can contribute to rhythmic activity in both neuronal and non-neuronal systems (Kelly and Wagner, 2002; Luthi et al., 1998; Luthi and McCormick, 1999; McCormick and Pape, 1990). GnRH neurons exhibit Ih (Chu et al., 2010; Zhang et al., 2007).
Over the past decade, the existence of transgenic mouse models in which reporter genes are expressed under the control of the gonadotropin-releasing hormone (GnRH) promoter has made possible the electrophysiological study of these cells. Here, we review the intrinsic and synaptic properties of these cells that have been revealed by these approaches, with a particular regard to burst generation. Advances in our understanding of neuromodulation of GnRH neurons and synchronization of this network are also discussed.
An integrated model of electrical spiking, bursting, and calcium oscillations in GnRH neurons
2009, Biophysical Journal
Citation Excerpt :
The T-type Ca2+ current has been implicated in phasic firing in thalamic neurons. It has been suggested that it may play a similar role in GnRH neurons (31). Although bursting has been reported in a variety of GnRH neuron preparations (2,18–20,32,33), no specific underlying mechanism has been derived.
The plasma membrane electrical activities of neurons that secrete gonadotropin-releasing hormone (GnRH) have been studied extensively. A couple of mathematical models have been developed previously to explain different aspects of these activities. The goal of this article is to develop a single model that accounts for the previously modeled experimental results and some more recent results that have not been accounted for. The latter includes two types of membrane potential bursting mechanisms and their associated cytosolic calcium oscillations. One bursting mechanism has not been reported in experiments and is thus regarded as a model prediction. Although the model is mainly based on data collected in immortalized GnRH cell lines, it is capable of explaining some properties of GnRH neurons observed in several other preparations including mature GnRH neurons in hypothalamic slices. We present a spatial model that incorporates a detailed description of calcium dynamics in a three-dimensional cell body with the ion channels evenly distributed on the cell surface. A phenomenological reduction of the spatial model into a simplified form is also presented. The simplified model will facilitate the study of the roles of plasma membrane electrical activities in the pulsatile release of GnRH.
Physiology of the gonadotropin-releasing hormone neuronal network
2006, Knobil and Neill's Physiology of Reproduction
Spike-dependent depolarizing afterpotentials contribute to endogenous bursting in gonadotropin releasing hormone neurons
2005, Neuroscience
Pulsatile secretion of gonadotropin releasing hormone in mammals is thought to depend on repetitive and prolonged bursts of action potentials in specific neuroendocrine cells. We have previously described episodes of electrical activity in isolated gonadotropin releasing hormone neurons, but the intrinsic mechanisms underlying the generation of spike bursts are unknown. In acutely isolated gonadotropin releasing hormone neurons, which had been genetically targeted to express enhanced green fluorescent protein, current pulses generated spike-mediated depolarizing afterpotentials in 69% of cells. Spike-dependent depolarizing afterpotentials could evoke bursts of action potentials that lasted for tens of seconds. Brief pulses of glutamate (as short as 1 ms), which simulated excitatory postsynaptic potentials, also triggered spike-mediated depolarizing afterpotentials and episodic activity. These data indicate that spike-dependent depolarizing afterpotentials, an endogenous mechanism in gonadotropin releasing hormone neurons, likely contribute to the episodic firing thought to underlie pulsatile secretion of gonadotropin releasing hormone. Furthermore, fast excitatory postsynaptic potentials mediated by glutamate can activate this intrinsic mechanism.

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Trends in Endocrinology & Metabolism

Research UpdateGnRH neurons and episodic bursting activity

Abstract

Brain Res.

Episodic bursting activity and response to excitatory amino acids in acutely dissociated gonadotropin-releasing hormone neurons genetically targeted with green fluorescent protein

J. Neurosci.

Whole-cell recordings from preoptic/hypothalamic slices reveal burst firing in gonadotropin-releasing hormone neurons identified with green fluorescent protein in transgenic mice

Endocrinology

GABA- and glutamate-activated channels in green fluorescent protein-tagged gonadotropin-releasing hormone neurons in transgenic mice

J. Neurosci.

Research Update
GnRH neurons and episodic bursting activity