Different dendritic domains of the GnRH neuron underlie the pulse and surge modes of GnRH secretion in female mice.

Li Wang,Xi Shen,Zhexuan Wang,Wenya Guo,Qifeng Lyu,Hui Long,Shel Yeo,Yanping Kuang,Allan E Herbison

doi:10.7554/elife.53945

Abstract

The gonadotropin-releasing hormone (GnRH) neurons exhibit pulse and surge modes of activity to control fertility. They also exhibit an unusual bipolar morphology comprised of a classical soma-proximal dendritic zone and an elongated secretory process that can operate as both a dendrite and an axon, termed a 'dendron'. We show using expansion microscopy that the highest density of synaptic inputs to a GnRH neuron exists at its distal dendron. In vivo, selective chemogenetic inhibition of the GnRH neuron distal dendron abolishes the luteinizing hormone (LH) surge and markedly dampens LH pulses. In contrast, inhibitory chemogenetic and optogenetic strategies targeting the GnRH neuron soma-proximal dendritic zone abolish the LH surge but have no effect upon LH pulsatility. These observations indicate that electrical activity at the soma-proximal dendrites of the GnRH neuron is only essential for the LH surge while the distal dendron represents an autonomous zone where synaptic integration drives pulsatile GnRH secretion.

Highlights

The gonadotropin-releasing hormone (GnRH) neurons represent the final output cells of a complex neuronal network that integrates a wide variety of internal and external factors to control the fertility of the individual (Herbison, 2016)
To examine the relative density of synaptic inputs at the dendron compared with more proximal compartments of the GnRH neuron, we used expansion microscopy (Chen et al, 2015; Chozinski et al, 2016) to generate high-resolution images of synaptophysin-immunoreactive terminals apposing GnRH neurons in adult diestrous female GnRH-GFP mice (N = 4)(Figure 1)
We analyzed 25 ‘side-on’ profiles where vesicular GABA transporter (VGAT) and gephyrin were opposed to one another, thereby, defining a synapse (Figure 1—figure supplement 1A). This revealed that the overlap between cytoplasmic GFP and the presynaptic marker VGAT must be >0.23 mm (0.95 mm post-expansion) to represent a synapse; the gephyrin signal was contained within the GFP signal and all 25 synapses had an overlap in VGAT and GFP signals > 0.23 mm (Figure 1—figure supplement 1A)

Summary

Introduction

The gonadotropin-releasing hormone (GnRH) neurons represent the final output cells of a complex neuronal network that integrates a wide variety of internal and external factors to control the fertility of the individual (Herbison, 2016). Recent studies in the mouse have highlighted that one or both of the dendritic processes arising from a GnRH neuron can project for over 4000 mm before terminating in short neurosecretory axons within the secretory zone of the median eminence (Herde et al, 2013; Moore et al, 2018b) These processes conduct action potentials from the soma-dendritic zone and receive synaptic inputs, with their blended dendritic/axonal properties leading them to be termed ‘dendrons’ (Herde et al, 2013). These morphological studies have raised the possibility that synaptic inputs directed at GnRH

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Results

Conclusion