Using ephaptic coupling to estimate the synaptic cleft resistivity of the calyx of Held synapse.

At synapses, the pre- and postsynaptic cells get so close that currents entering the cleft do not flow exclusively along its conductance, gcl. A prominent example is found in the calyx of Held synapse in the medial nucleus of the trapezoid body (MNTB), where the presynaptic action potential can be r...

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Autores principales:	Martijn C Sierksma, J Gerard G Borst
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/84fdac5b770142f1b49a1fbb9b75ed78
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spelling	oai:doaj.org-article:84fdac5b770142f1b49a1fbb9b75ed782021-12-02T19:57:41ZUsing ephaptic coupling to estimate the synaptic cleft resistivity of the calyx of Held synapse.1553-734X1553-735810.1371/journal.pcbi.1009527https://doaj.org/article/84fdac5b770142f1b49a1fbb9b75ed782021-10-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1009527https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358At synapses, the pre- and postsynaptic cells get so close that currents entering the cleft do not flow exclusively along its conductance, gcl. A prominent example is found in the calyx of Held synapse in the medial nucleus of the trapezoid body (MNTB), where the presynaptic action potential can be recorded in the postsynaptic cell in the form of a prespike. Here, we developed a theoretical framework for ephaptic coupling via the synaptic cleft, and we tested its predictions using the MNTB prespike recorded in voltage-clamp. The shape of the prespike is predicted to resemble either the first or the second derivative of the inverted presynaptic action potential if cleft currents dissipate either mostly capacitively or resistively, respectively. We found that the resistive dissipation scenario provided a better description of the prespike shape. Its size is predicted to scale with the fourth power of the radius of the synapse, explaining why intracellularly recorded prespikes are uncommon in the central nervous system. We show that presynaptic calcium currents also contribute to the prespike shape. This calcium prespike resembled the first derivative of the inverted calcium current, again as predicted by the resistive dissipation scenario. Using this calcium prespike, we obtained an estimate for gcl of ~1 μS. We demonstrate that, for a circular synapse geometry, such as in conventional boutons or the immature calyx of Held, gcl is scale-invariant and only defined by extracellular resistivity, which was ~75 Ωcm, and by cleft height. During development the calyx of Held develops fenestrations. We show that these fenestrations effectively minimize the cleft potentials generated by the adult action potential, which might otherwise interfere with calcium channel opening. We thus provide a quantitative account of the dissipation of currents by the synaptic cleft, which can be readily extrapolated to conventional, bouton-like synapses.Martijn C SierksmaJ Gerard G BorstPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 17, Iss 10, p e1009527 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Martijn C Sierksma J Gerard G Borst Using ephaptic coupling to estimate the synaptic cleft resistivity of the calyx of Held synapse.
description	At synapses, the pre- and postsynaptic cells get so close that currents entering the cleft do not flow exclusively along its conductance, gcl. A prominent example is found in the calyx of Held synapse in the medial nucleus of the trapezoid body (MNTB), where the presynaptic action potential can be recorded in the postsynaptic cell in the form of a prespike. Here, we developed a theoretical framework for ephaptic coupling via the synaptic cleft, and we tested its predictions using the MNTB prespike recorded in voltage-clamp. The shape of the prespike is predicted to resemble either the first or the second derivative of the inverted presynaptic action potential if cleft currents dissipate either mostly capacitively or resistively, respectively. We found that the resistive dissipation scenario provided a better description of the prespike shape. Its size is predicted to scale with the fourth power of the radius of the synapse, explaining why intracellularly recorded prespikes are uncommon in the central nervous system. We show that presynaptic calcium currents also contribute to the prespike shape. This calcium prespike resembled the first derivative of the inverted calcium current, again as predicted by the resistive dissipation scenario. Using this calcium prespike, we obtained an estimate for gcl of ~1 μS. We demonstrate that, for a circular synapse geometry, such as in conventional boutons or the immature calyx of Held, gcl is scale-invariant and only defined by extracellular resistivity, which was ~75 Ωcm, and by cleft height. During development the calyx of Held develops fenestrations. We show that these fenestrations effectively minimize the cleft potentials generated by the adult action potential, which might otherwise interfere with calcium channel opening. We thus provide a quantitative account of the dissipation of currents by the synaptic cleft, which can be readily extrapolated to conventional, bouton-like synapses.
format	article
author	Martijn C Sierksma J Gerard G Borst
author_facet	Martijn C Sierksma J Gerard G Borst
author_sort	Martijn C Sierksma
title	Using ephaptic coupling to estimate the synaptic cleft resistivity of the calyx of Held synapse.
title_short	Using ephaptic coupling to estimate the synaptic cleft resistivity of the calyx of Held synapse.
title_full	Using ephaptic coupling to estimate the synaptic cleft resistivity of the calyx of Held synapse.
title_fullStr	Using ephaptic coupling to estimate the synaptic cleft resistivity of the calyx of Held synapse.
title_full_unstemmed	Using ephaptic coupling to estimate the synaptic cleft resistivity of the calyx of Held synapse.
title_sort	using ephaptic coupling to estimate the synaptic cleft resistivity of the calyx of held synapse.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/84fdac5b770142f1b49a1fbb9b75ed78
work_keys_str_mv	AT martijncsierksma usingephapticcouplingtoestimatethesynapticcleftresistivityofthecalyxofheldsynapse AT jgerardgborst usingephapticcouplingtoestimatethesynapticcleftresistivityofthecalyxofheldsynapse
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Using ephaptic coupling to estimate the synaptic cleft resistivity of the calyx of Held synapse.

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