The increase in the number of spines on the gonadotropin-releasing hormone neuron across pubertal development in rats

Abstract

The onset of puberty is initiated by an increase in the release of the gonadotropin-releasing hormone (GnRH) from GnRH neurons in the hypothalamus. However, the precise mechanism that leads to the activation of GnRH neurons at puberty remains controversial. Spines are small protrusions on the surface of dendrites that normally receive excitatory inputs. In this study, we analyzed the number and morphology of spines on GnRH neurons to investigate changes in synaptic inputs across puberty in rats. For morphological estimation, we measured the diameter of the head (DH) of each spine and classified them into small-type (DH < 0.65 μm), large-type (DH > 0.65 μm) and giant-type (DH > 0.9 μm). The greatest number of spines was observed at the proximal dendrite within 50 μm of the soma. At the soma and proximal dendrite, the number of spines was greater in adults than in juveniles in both male and female individuals. Classification of spines revealed that the increase in spine number was due to increases in large- and giant-type spines. To further explore the relationship between spines on GnRH neurons and pubertal development, we next analyzed adult rats neonatally exposed to estradiol benzoate, in which puberty onset and reproductive functions are disrupted. We found a decrease in the number of all types of spines. These results suggest that GnRH neurons become to receive more and greater excitatory inputs on the soma and proximal dendrites as a result of the changes that occur at puberty and that alteration to spines plays a pivotal role in normal pubertal development.

Altered GnRH neuron and ovarian innervation characterize reproductive dysfunction linked to the Fragile X messenger ribonucleoprotein (Fmr1) gene mutation

“…We determined that GABAg2 puncta numbers increased significantly in the GnRH neuron soma and in the first 15 mm of the process proximal to the soma (Figure 9C quantification, Figure 9B, representative images, top WT, bottom Fmr1 KO). The increase in GABAergic inputs in this area is significant, since this region of the neuron is the region where action potentials are initiated (88), and it exhibits synaptic plasticity during development and in different hormonal milieu (89)(90)(91). Since GABA is excitatory for GnRH neurons (20,(26)(27)(28), the alteration of the receptor levels may enhance GnRH neuron responsiveness and neuropeptide secretion, which in turn would cause changes in gonadotropin levels.…”

α4βδ GABAA Receptors Trigger Synaptic Pruning and Reduce Dendritic Length of Female Mouse CA3 Hippocampal Pyramidal Cells at Puberty

“…A number of recent studies have also pinpointed puberty onset as the trigger for synapse loss in medial amygdala (Zancan et al, 2018), medial prefrontal cortex (Drzewiecki et al, 2016) and dorsomedial frontal cortex (Boivin et al, 2018). Interestingly, puberty onset is associated with an increase in spine density of gonadotropic hormone-containing neurons in the hypothalamus (Li et al, 2016).…”

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

“…The GnRH neurons exhibit a bipolar morphology with synaptic inputs clustered around the soma and proximal dendrites ( Campbell et al, 2005 ; Li et al, 2016 ; Moore et al, 2015 ) and the action potential initiation site located 50–100 μm down one of the dendritic processes ( Herde and Herbison, 2015 ; Iremonger and Herbison, 2012 ; Roberts et al, 2008 ). To date, synaptic integration within this soma-dendritic zone of the GnRH neuron has been the prime focus of attention in understanding how these cells generate pulse and surge modes of GnRH release.…”