5-HT7 receptor modulates GABAergic transmission in the rat dorsal raphe nucleus and controls cortical release of serotonin

The 5-HT7 receptor is one of the several serotonin (5-HT) receptor subtypes that are expressed in the dorsal raphe nucleus (DRN). Some earlier findings suggested that 5-HT7 receptors in the DRN were localized on GABAergic interneurons modulating the activity of 5-HT projection neurons. The aim of th...

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Main Authors: Magdalena Kusek, Joanna Sowa, Katarzyna Kamińska, Krystyna Gołembiowska, Krzysztof Tokarski, Grzegorz Hess
Format: Article
Language:English
Published: Frontiers Media S.A. 2015-08-01
Series:Frontiers in Cellular Neuroscience
Subjects:
Online Access:http://journal.frontiersin.org/article/10.3389/fncel.2015.00324/full
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author Magdalena Kusek
Joanna Sowa
Katarzyna Kamińska
Krystyna Gołembiowska
Krzysztof Tokarski
Grzegorz Hess
Grzegorz Hess
author_facet Magdalena Kusek
Joanna Sowa
Katarzyna Kamińska
Krystyna Gołembiowska
Krzysztof Tokarski
Grzegorz Hess
Grzegorz Hess
author_sort Magdalena Kusek
collection DOAJ
description The 5-HT7 receptor is one of the several serotonin (5-HT) receptor subtypes that are expressed in the dorsal raphe nucleus (DRN). Some earlier findings suggested that 5-HT7 receptors in the DRN were localized on GABAergic interneurons modulating the activity of 5-HT projection neurons. The aim of the present study was to find out how the 5-HT7 receptor modulates the GABAergic synaptic input to putative 5-HT DRN neurons, and whether blockade of the 5-HT7 receptor would affect the release of 5-HT in the target structure. Male Wistar rats with microdialysis probes implanted in the prefrontal cortex (PFC) received injections of the 5-HT7 receptor antagonist (2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine hydrochloride (SB 269970), which induced an increase in the levels of 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA) in the PFC. In another set of experiments whole-cell recordings from presumed projection neurons were carried out using DRN slices. SB 269970 application resulted in depolarization and in an increase in the firing frequency of the cells. In order to activate 5-HT7 receptors, 5-carboxamidotryptamine (5-CT) was applied in the presence of N-[2-[4-(2-methoxyphenyl)-1piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide (WAY100635). Hyperpolarization of cells and a decrease in the firing frequency were observed after activation of the 5-HT7 receptor. Blockade of 5-HT7 receptors caused a decrease in the mean frequency of spontaneous inhibitory postsynaptic currents (sIPSCs), while its activation induced an increase. The mechanism of these effects appears to involve tonically-active 5-HT7 receptors modulating firing and/or GABA release from inhibitory interneurons which regulate the activity of DRN serotonergic projection neurons.
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spelling doaj.art-4d283609313540a7af8985f3914116742022-12-22T02:58:39ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022015-08-01910.3389/fncel.2015.003241540595-HT7 receptor modulates GABAergic transmission in the rat dorsal raphe nucleus and controls cortical release of serotoninMagdalena Kusek0Joanna Sowa1Katarzyna Kamińska2Krystyna Gołembiowska3Krzysztof Tokarski4Grzegorz Hess5Grzegorz Hess6Department of Physiology, Institute of Pharmacology, Polish Academy of SciencesKrakow, PolandDepartment of Physiology, Institute of Pharmacology, Polish Academy of SciencesKrakow, PolandDepartment of Pharmacology, Institute of Pharmacology, Polish Academy of SciencesKrakow, PolandDepartment of Pharmacology, Institute of Pharmacology, Polish Academy of SciencesKrakow, PolandDepartment of Physiology, Institute of Pharmacology, Polish Academy of SciencesKrakow, PolandDepartment of Physiology, Institute of Pharmacology, Polish Academy of SciencesKrakow, PolandInstitute of Zoology, Jagiellonian UniversityKrakow, PolandThe 5-HT7 receptor is one of the several serotonin (5-HT) receptor subtypes that are expressed in the dorsal raphe nucleus (DRN). Some earlier findings suggested that 5-HT7 receptors in the DRN were localized on GABAergic interneurons modulating the activity of 5-HT projection neurons. The aim of the present study was to find out how the 5-HT7 receptor modulates the GABAergic synaptic input to putative 5-HT DRN neurons, and whether blockade of the 5-HT7 receptor would affect the release of 5-HT in the target structure. Male Wistar rats with microdialysis probes implanted in the prefrontal cortex (PFC) received injections of the 5-HT7 receptor antagonist (2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine hydrochloride (SB 269970), which induced an increase in the levels of 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA) in the PFC. In another set of experiments whole-cell recordings from presumed projection neurons were carried out using DRN slices. SB 269970 application resulted in depolarization and in an increase in the firing frequency of the cells. In order to activate 5-HT7 receptors, 5-carboxamidotryptamine (5-CT) was applied in the presence of N-[2-[4-(2-methoxyphenyl)-1piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide (WAY100635). Hyperpolarization of cells and a decrease in the firing frequency were observed after activation of the 5-HT7 receptor. Blockade of 5-HT7 receptors caused a decrease in the mean frequency of spontaneous inhibitory postsynaptic currents (sIPSCs), while its activation induced an increase. The mechanism of these effects appears to involve tonically-active 5-HT7 receptors modulating firing and/or GABA release from inhibitory interneurons which regulate the activity of DRN serotonergic projection neurons.http://journal.frontiersin.org/article/10.3389/fncel.2015.00324/fullbrain slicesHPLCmicrodialysisprefrontal cortexwhole-cell recording
spellingShingle Magdalena Kusek
Joanna Sowa
Katarzyna Kamińska
Krystyna Gołembiowska
Krzysztof Tokarski
Grzegorz Hess
Grzegorz Hess
5-HT7 receptor modulates GABAergic transmission in the rat dorsal raphe nucleus and controls cortical release of serotonin
Frontiers in Cellular Neuroscience
brain slices
HPLC
microdialysis
prefrontal cortex
whole-cell recording
title 5-HT7 receptor modulates GABAergic transmission in the rat dorsal raphe nucleus and controls cortical release of serotonin
title_full 5-HT7 receptor modulates GABAergic transmission in the rat dorsal raphe nucleus and controls cortical release of serotonin
title_fullStr 5-HT7 receptor modulates GABAergic transmission in the rat dorsal raphe nucleus and controls cortical release of serotonin
title_full_unstemmed 5-HT7 receptor modulates GABAergic transmission in the rat dorsal raphe nucleus and controls cortical release of serotonin
title_short 5-HT7 receptor modulates GABAergic transmission in the rat dorsal raphe nucleus and controls cortical release of serotonin
title_sort 5 ht7 receptor modulates gabaergic transmission in the rat dorsal raphe nucleus and controls cortical release of serotonin
topic brain slices
HPLC
microdialysis
prefrontal cortex
whole-cell recording
url http://journal.frontiersin.org/article/10.3389/fncel.2015.00324/full
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