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SUN-247 GABA Receptor-Dependent Inhibition and Excitation of GnRH Neuron Dendrons near the Median Eminence in Mice
The gonadotrophin-releasing hormone (GnRH) neuron cell bodies are scattered throughout the basal forebrain but funnel their projections to the median eminence to control fertility in all mammals. In mice, these long projections, termed “dendrons”, have characteristics of both dendrites and axons and...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7208841/ http://dx.doi.org/10.1210/jendso/bvaa046.407 |
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author | Liu, Xinhuai Porteous, Robert Herbison, Allan Edward |
author_facet | Liu, Xinhuai Porteous, Robert Herbison, Allan Edward |
author_sort | Liu, Xinhuai |
collection | PubMed |
description | The gonadotrophin-releasing hormone (GnRH) neuron cell bodies are scattered throughout the basal forebrain but funnel their projections to the median eminence to control fertility in all mammals. In mice, these long projections, termed “dendrons”, have characteristics of both dendrites and axons and are found to receive large numbers of synaptic inputs just prior to entering the median eminence. While the effects of many neurotransmitters have been documented at the GnRH neuron cell body, very little is known about the neural control of the distal dendron. To examine the role of amino acid neurotransmitters in the regulation of the thin GnRH neuron distal dendrons, we used confocal microscopy in combination with real-time GCaMP6 calcium imaging in acute horizontal brain slices. Adult male and female GnRH-Cre mice were given stereotaxic injections of a Cre-dependent AAV expressing GCaMP6s and, > 3 weeks later, the brain removed and a single thick horizontal brain slice prepared that included the base of the brain and median eminence. The intracellular calcium levels of multiple dendrons were monitored simultaneously while puffs of amino acid receptor agonists were applied. Surprisingly, GABA exhibited a dual action on calcium concentrations with an initial transient increase followed by a prolonged decrease and subsequent rebound. The administration of GABA(A) and GABA(B) receptor agonist and antagonists revealed that the transient increase resulted from a quickly desensitizing activation of GABA(A) receptors while the decrease and subsequent rebound was dependent upon the slower kinetics of the GABA(B) receptor. Kisspeptin exerts a potent long-lasting elevation of calcium levels in GnRH dendrons and this was robustly inhibited by subsequent GABA(B) receptor activation. In contrast to GABA, glutamate was not found to have any impact on intracellular calcium levels in the distal dendrons and, similarly, the activation of NMDA or AMPA receptors was found to be ineffective. The results show that GABA exerts particularly potent modulatory actions upon basal and evoked calcium concentrations within the GnRH neuron distal dendron. This suggests that acute brief activation of the dendron by GABA would facilitate GnRH release through GABA(A) receptor activation whereas prolonged GABA release would suppress activity through the GABA(B) receptor. As such, GABA inputs to the distal dendron appear likely to play a major role in the control of GnRH secretion in the mouse. |
format | Online Article Text |
id | pubmed-7208841 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-72088412020-05-13 SUN-247 GABA Receptor-Dependent Inhibition and Excitation of GnRH Neuron Dendrons near the Median Eminence in Mice Liu, Xinhuai Porteous, Robert Herbison, Allan Edward J Endocr Soc Neuroendocrinology and Pituitary The gonadotrophin-releasing hormone (GnRH) neuron cell bodies are scattered throughout the basal forebrain but funnel their projections to the median eminence to control fertility in all mammals. In mice, these long projections, termed “dendrons”, have characteristics of both dendrites and axons and are found to receive large numbers of synaptic inputs just prior to entering the median eminence. While the effects of many neurotransmitters have been documented at the GnRH neuron cell body, very little is known about the neural control of the distal dendron. To examine the role of amino acid neurotransmitters in the regulation of the thin GnRH neuron distal dendrons, we used confocal microscopy in combination with real-time GCaMP6 calcium imaging in acute horizontal brain slices. Adult male and female GnRH-Cre mice were given stereotaxic injections of a Cre-dependent AAV expressing GCaMP6s and, > 3 weeks later, the brain removed and a single thick horizontal brain slice prepared that included the base of the brain and median eminence. The intracellular calcium levels of multiple dendrons were monitored simultaneously while puffs of amino acid receptor agonists were applied. Surprisingly, GABA exhibited a dual action on calcium concentrations with an initial transient increase followed by a prolonged decrease and subsequent rebound. The administration of GABA(A) and GABA(B) receptor agonist and antagonists revealed that the transient increase resulted from a quickly desensitizing activation of GABA(A) receptors while the decrease and subsequent rebound was dependent upon the slower kinetics of the GABA(B) receptor. Kisspeptin exerts a potent long-lasting elevation of calcium levels in GnRH dendrons and this was robustly inhibited by subsequent GABA(B) receptor activation. In contrast to GABA, glutamate was not found to have any impact on intracellular calcium levels in the distal dendrons and, similarly, the activation of NMDA or AMPA receptors was found to be ineffective. The results show that GABA exerts particularly potent modulatory actions upon basal and evoked calcium concentrations within the GnRH neuron distal dendron. This suggests that acute brief activation of the dendron by GABA would facilitate GnRH release through GABA(A) receptor activation whereas prolonged GABA release would suppress activity through the GABA(B) receptor. As such, GABA inputs to the distal dendron appear likely to play a major role in the control of GnRH secretion in the mouse. Oxford University Press 2020-05-08 /pmc/articles/PMC7208841/ http://dx.doi.org/10.1210/jendso/bvaa046.407 Text en © Endocrine Society 2020. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Neuroendocrinology and Pituitary Liu, Xinhuai Porteous, Robert Herbison, Allan Edward SUN-247 GABA Receptor-Dependent Inhibition and Excitation of GnRH Neuron Dendrons near the Median Eminence in Mice |
title | SUN-247 GABA Receptor-Dependent Inhibition and Excitation of GnRH Neuron Dendrons near the Median Eminence in Mice |
title_full | SUN-247 GABA Receptor-Dependent Inhibition and Excitation of GnRH Neuron Dendrons near the Median Eminence in Mice |
title_fullStr | SUN-247 GABA Receptor-Dependent Inhibition and Excitation of GnRH Neuron Dendrons near the Median Eminence in Mice |
title_full_unstemmed | SUN-247 GABA Receptor-Dependent Inhibition and Excitation of GnRH Neuron Dendrons near the Median Eminence in Mice |
title_short | SUN-247 GABA Receptor-Dependent Inhibition and Excitation of GnRH Neuron Dendrons near the Median Eminence in Mice |
title_sort | sun-247 gaba receptor-dependent inhibition and excitation of gnrh neuron dendrons near the median eminence in mice |
topic | Neuroendocrinology and Pituitary |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7208841/ http://dx.doi.org/10.1210/jendso/bvaa046.407 |
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