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Local kisspeptin excitation of rat oxytocin neurones in late pregnancy
ABSTRACT: The hormone, oxytocin, is synthesised by magnocellular neurones of the supraoptic and paraventricular nuclei and is released from the posterior pituitary gland into the circulation to trigger uterine contractions during parturition. Kisspeptin fibre density increases around the supraoptic...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303251/ https://www.ncbi.nlm.nih.gov/pubmed/35045190 http://dx.doi.org/10.1113/JP282531 |
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author | Abbasi, Mehwish Perkinson, Michael R. Seymour, Alexander J. Piet, Richard Campbell, Rebecca E. Iremonger, Karl J. Brown, Colin H. |
author_facet | Abbasi, Mehwish Perkinson, Michael R. Seymour, Alexander J. Piet, Richard Campbell, Rebecca E. Iremonger, Karl J. Brown, Colin H. |
author_sort | Abbasi, Mehwish |
collection | PubMed |
description | ABSTRACT: The hormone, oxytocin, is synthesised by magnocellular neurones of the supraoptic and paraventricular nuclei and is released from the posterior pituitary gland into the circulation to trigger uterine contractions during parturition. Kisspeptin fibre density increases around the supraoptic nucleus over pregnancy and intracerebroventricular kisspeptin excites oxytocin neurones only in late pregnancy. However, the mechanism of this excitation is unknown. Here, we found that microdialysis administration of kisspeptin into the supraoptic nucleus consistently increased the action potential (spike) firing rate of oxytocin neurones in urethane‐anaesthetised late‐pregnant rats (gestation day 18–21) but not in non‐pregnant rats. Hazard analysis of action potential firing showed that kisspeptin specifically increased the probability of another action potential firing immediately after each action potential (post‐spike excitability) in late‐pregnant rats. Patch‐clamp electrophysiology in hypothalamic slices showed that bath application of kisspeptin did not affect action potential frequency or baseline membrane potential in supraoptic nucleus neurones. Moreover, kisspeptin superfusion did not affect the frequency or amplitude of excitatory postsynaptic currents or inhibitory postsynaptic currents in supraoptic nucleus neurones. Taken together, these studies suggest that kisspeptin directly activates oxytocin neurones in late pregnancy, at least in part, via increased post‐spike excitability. KEY POINTS: Oxytocin secretion is triggered by action potential firing in magnocellular neurones of the hypothalamic supraoptic and paraventricular nuclei to induce uterine contractions during birth. In late pregnancy, kisspeptin expression increases in rat periventricular nucleus neurones that project to the oxytocin system. Here, we show that intra‐supraoptic nucleus administration of kisspeptin increases the action potential firing rate of oxytocin neurones in anaesthetised late‐pregnant rats, and that the increased firing rate is associated with increased oxytocin neurone excitability immediately after each action potential. By contrast, kisspeptin superfusion of hypothalamic slices did not affect the activity of supraoptic nucleus neurones or the strength of local synaptic inputs to supraoptic nucleus neurones. Hence, kisspeptin might activate oxytocin neurons in late pregnancy by transiently increasing oxytocin neuron excitability after each action potential. |
format | Online Article Text |
id | pubmed-9303251 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93032512022-07-22 Local kisspeptin excitation of rat oxytocin neurones in late pregnancy Abbasi, Mehwish Perkinson, Michael R. Seymour, Alexander J. Piet, Richard Campbell, Rebecca E. Iremonger, Karl J. Brown, Colin H. J Physiol Neuroscience ABSTRACT: The hormone, oxytocin, is synthesised by magnocellular neurones of the supraoptic and paraventricular nuclei and is released from the posterior pituitary gland into the circulation to trigger uterine contractions during parturition. Kisspeptin fibre density increases around the supraoptic nucleus over pregnancy and intracerebroventricular kisspeptin excites oxytocin neurones only in late pregnancy. However, the mechanism of this excitation is unknown. Here, we found that microdialysis administration of kisspeptin into the supraoptic nucleus consistently increased the action potential (spike) firing rate of oxytocin neurones in urethane‐anaesthetised late‐pregnant rats (gestation day 18–21) but not in non‐pregnant rats. Hazard analysis of action potential firing showed that kisspeptin specifically increased the probability of another action potential firing immediately after each action potential (post‐spike excitability) in late‐pregnant rats. Patch‐clamp electrophysiology in hypothalamic slices showed that bath application of kisspeptin did not affect action potential frequency or baseline membrane potential in supraoptic nucleus neurones. Moreover, kisspeptin superfusion did not affect the frequency or amplitude of excitatory postsynaptic currents or inhibitory postsynaptic currents in supraoptic nucleus neurones. Taken together, these studies suggest that kisspeptin directly activates oxytocin neurones in late pregnancy, at least in part, via increased post‐spike excitability. KEY POINTS: Oxytocin secretion is triggered by action potential firing in magnocellular neurones of the hypothalamic supraoptic and paraventricular nuclei to induce uterine contractions during birth. In late pregnancy, kisspeptin expression increases in rat periventricular nucleus neurones that project to the oxytocin system. Here, we show that intra‐supraoptic nucleus administration of kisspeptin increases the action potential firing rate of oxytocin neurones in anaesthetised late‐pregnant rats, and that the increased firing rate is associated with increased oxytocin neurone excitability immediately after each action potential. By contrast, kisspeptin superfusion of hypothalamic slices did not affect the activity of supraoptic nucleus neurones or the strength of local synaptic inputs to supraoptic nucleus neurones. Hence, kisspeptin might activate oxytocin neurons in late pregnancy by transiently increasing oxytocin neuron excitability after each action potential. John Wiley and Sons Inc. 2022-02-03 2022-04-01 /pmc/articles/PMC9303251/ /pubmed/35045190 http://dx.doi.org/10.1113/JP282531 Text en © 2022 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Neuroscience Abbasi, Mehwish Perkinson, Michael R. Seymour, Alexander J. Piet, Richard Campbell, Rebecca E. Iremonger, Karl J. Brown, Colin H. Local kisspeptin excitation of rat oxytocin neurones in late pregnancy |
title | Local kisspeptin excitation of rat oxytocin neurones in late pregnancy |
title_full | Local kisspeptin excitation of rat oxytocin neurones in late pregnancy |
title_fullStr | Local kisspeptin excitation of rat oxytocin neurones in late pregnancy |
title_full_unstemmed | Local kisspeptin excitation of rat oxytocin neurones in late pregnancy |
title_short | Local kisspeptin excitation of rat oxytocin neurones in late pregnancy |
title_sort | local kisspeptin excitation of rat oxytocin neurones in late pregnancy |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303251/ https://www.ncbi.nlm.nih.gov/pubmed/35045190 http://dx.doi.org/10.1113/JP282531 |
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