Spike triggered hormone secretion in vasopressin cells; a model investigation of mechanism and heterogeneous population function.

Vasopressin neurons generate distinctive phasic patterned spike activity in response to elevated extracellular osmotic pressure. These spikes are generated in the cell body and are conducted down the axon to the axonal terminals where they trigger Ca²⁺ entry and subsequent exocytosis of hormone-cont...

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Autores principales:	Duncan J MacGregor, Gareth Leng
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/c6029b66602d4b3f846810ebcb902642
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spelling	oai:doaj.org-article:c6029b66602d4b3f846810ebcb9026422021-11-18T05:53:40ZSpike triggered hormone secretion in vasopressin cells; a model investigation of mechanism and heterogeneous population function.1553-734X1553-735810.1371/journal.pcbi.1003187https://doaj.org/article/c6029b66602d4b3f846810ebcb9026422013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23966850/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Vasopressin neurons generate distinctive phasic patterned spike activity in response to elevated extracellular osmotic pressure. These spikes are generated in the cell body and are conducted down the axon to the axonal terminals where they trigger Ca²⁺ entry and subsequent exocytosis of hormone-containing vesicles and secretion of vasopressin. This mechanism is highly non-linear, subject to both frequency facilitation and fatigue, such that the rate of secretion depends on both the rate and patterning of the spike activity. Here we used computational modelling to investigate this relationship and how it shapes the overall response of the neuronal population. We generated a concise single compartment model of the secretion mechanism, fitted to experimentally observed profiles of facilitation and fatigue, and based on representations of the hypothesised underlying mechanisms. These mechanisms include spike broadening, Ca²⁺ channel inactivation, a Ca²⁺ sensitive K⁺ current, and releasable and reserve pools of vesicles. We coupled the secretion model to an existing integrate-and-fire based spiking model in order to study the secretion response to increasing synaptic input, and compared phasic and non-phasic spiking models to assess the functional value of the phasic spiking pattern. The secretory response of individual phasic cells is very non-linear, but the response of a heterogeneous population of phasic cells shows a much more linear response to increasing input, matching the linear response we observe experimentally, though in this respect, phasic cells have no apparent advantage over non-phasic cells. Another challenge for the cells is maintaining this linear response during chronic stimulation, and we show that the activity-dependent fatigue mechanism has a potentially useful function in helping to maintain secretion despite depletion of stores. Without this mechanism, secretion in response to a steady stimulus declines as the stored content declines.Duncan J MacGregorGareth LengPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 9, Iss 8, p e1003187 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Duncan J MacGregor Gareth Leng Spike triggered hormone secretion in vasopressin cells; a model investigation of mechanism and heterogeneous population function.
description	Vasopressin neurons generate distinctive phasic patterned spike activity in response to elevated extracellular osmotic pressure. These spikes are generated in the cell body and are conducted down the axon to the axonal terminals where they trigger Ca²⁺ entry and subsequent exocytosis of hormone-containing vesicles and secretion of vasopressin. This mechanism is highly non-linear, subject to both frequency facilitation and fatigue, such that the rate of secretion depends on both the rate and patterning of the spike activity. Here we used computational modelling to investigate this relationship and how it shapes the overall response of the neuronal population. We generated a concise single compartment model of the secretion mechanism, fitted to experimentally observed profiles of facilitation and fatigue, and based on representations of the hypothesised underlying mechanisms. These mechanisms include spike broadening, Ca²⁺ channel inactivation, a Ca²⁺ sensitive K⁺ current, and releasable and reserve pools of vesicles. We coupled the secretion model to an existing integrate-and-fire based spiking model in order to study the secretion response to increasing synaptic input, and compared phasic and non-phasic spiking models to assess the functional value of the phasic spiking pattern. The secretory response of individual phasic cells is very non-linear, but the response of a heterogeneous population of phasic cells shows a much more linear response to increasing input, matching the linear response we observe experimentally, though in this respect, phasic cells have no apparent advantage over non-phasic cells. Another challenge for the cells is maintaining this linear response during chronic stimulation, and we show that the activity-dependent fatigue mechanism has a potentially useful function in helping to maintain secretion despite depletion of stores. Without this mechanism, secretion in response to a steady stimulus declines as the stored content declines.
format	article
author	Duncan J MacGregor Gareth Leng
author_facet	Duncan J MacGregor Gareth Leng
author_sort	Duncan J MacGregor
title	Spike triggered hormone secretion in vasopressin cells; a model investigation of mechanism and heterogeneous population function.
title_short	Spike triggered hormone secretion in vasopressin cells; a model investigation of mechanism and heterogeneous population function.
title_full	Spike triggered hormone secretion in vasopressin cells; a model investigation of mechanism and heterogeneous population function.
title_fullStr	Spike triggered hormone secretion in vasopressin cells; a model investigation of mechanism and heterogeneous population function.
title_full_unstemmed	Spike triggered hormone secretion in vasopressin cells; a model investigation of mechanism and heterogeneous population function.
title_sort	spike triggered hormone secretion in vasopressin cells; a model investigation of mechanism and heterogeneous population function.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/c6029b66602d4b3f846810ebcb902642
work_keys_str_mv	AT duncanjmacgregor spiketriggeredhormonesecretioninvasopressincellsamodelinvestigationofmechanismandheterogeneouspopulationfunction AT garethleng spiketriggeredhormonesecretioninvasopressincellsamodelinvestigationofmechanismandheterogeneouspopulationfunction
_version_	1718424692980711424

Spike triggered hormone secretion in vasopressin cells; a model investigation of mechanism and heterogeneous population function.

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