The selective neurotoxin DSP-4 impairs the noradrenergic projections from the locus coeruleus to the inferior colliculus in rats
Autor(a) principal: | |
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Data de Publicação: | 2012 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.3389/fncir.2012.00041 http://hdl.handle.net/11449/42441 |
Resumo: | The inferior colliculus (IC) and the locus coeruleus (LC) are two midbrain nuclei that integrate multimodal information and play a major role in novelty detection to elicit an orienting response. Despite the reciprocal connections between these two structures, the projection pattern and target areas of the LC within the subdivisions of the rat IC are still unknown. Here, we used tract-tracing approaches combined with immunohistochemistry, densitometry, and confocal microscopy (CM) analysis to describe a projection from the LC to the IC. Biotinylated dextran amine (BDA) injections into the LC showed that the LC-IC projection is mainly ipsilateral (90%) and reaches, to a major extent, the dorsal and lateral part of the IC and the intercollicular commissure. Additionally, some LC fibers extend into the central nucleus of the IC. The neurochemical nature of this projection is noradrenergic, given that tyrosine hydroxylase (TH) and dopamine beta hydroxylase (DBH) colocalize with the BDA-Iabeled fibers from the LC. To determine the total field of the LC innervations in the IC, we destroyed the LC neurons and fibers using a highly selective neurotoxin, DSP-4, and then studied the distribution and density of TH- and DBH-immunolabeled axons in the IC. In the DSP-4 treated animals, the number of axonal fibers immunolabeled for TH and DBH were deeply decreased throughout the entire rostrocaudal extent of the IC and its subdivisions compared to controls. Our densitometry results showed that the IC receives up to 97% of its noradrenergic innervations from the LC neurons and only 3% from non-coeruleus neurons. Our results also indicate that TH immunoreactivity in the IC was less impaired than the immunoreactivity for DBH after DSP-4 administration. This is consistent with the existence of an important dopaminergic projection from the substantia nigra to the IC. In conclusion, our study demonstrates and quantifies the noradrenergic projection from the LC to the IC and its subdivisions. The re-examination of the TH and DBH immunoreactivity after DSP-4 treatment provides insights into the source, extent, and topographic distribution of the LC efferent network in the IC, and hence, contributes to our understanding of the role of the noradrenaline (NA) system in auditory processing. |
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The selective neurotoxin DSP-4 impairs the noradrenergic projections from the locus coeruleus to the inferior colliculus in ratsbiotinylated dextran aminedopamine beta hydroxylase deficiencyimmunohistochemistrydensitometryneurotoxicitynoradrenergic efferentsnoradrenergic modulationtyrosine hydroxylaseThe inferior colliculus (IC) and the locus coeruleus (LC) are two midbrain nuclei that integrate multimodal information and play a major role in novelty detection to elicit an orienting response. Despite the reciprocal connections between these two structures, the projection pattern and target areas of the LC within the subdivisions of the rat IC are still unknown. Here, we used tract-tracing approaches combined with immunohistochemistry, densitometry, and confocal microscopy (CM) analysis to describe a projection from the LC to the IC. Biotinylated dextran amine (BDA) injections into the LC showed that the LC-IC projection is mainly ipsilateral (90%) and reaches, to a major extent, the dorsal and lateral part of the IC and the intercollicular commissure. Additionally, some LC fibers extend into the central nucleus of the IC. The neurochemical nature of this projection is noradrenergic, given that tyrosine hydroxylase (TH) and dopamine beta hydroxylase (DBH) colocalize with the BDA-Iabeled fibers from the LC. To determine the total field of the LC innervations in the IC, we destroyed the LC neurons and fibers using a highly selective neurotoxin, DSP-4, and then studied the distribution and density of TH- and DBH-immunolabeled axons in the IC. In the DSP-4 treated animals, the number of axonal fibers immunolabeled for TH and DBH were deeply decreased throughout the entire rostrocaudal extent of the IC and its subdivisions compared to controls. Our densitometry results showed that the IC receives up to 97% of its noradrenergic innervations from the LC neurons and only 3% from non-coeruleus neurons. Our results also indicate that TH immunoreactivity in the IC was less impaired than the immunoreactivity for DBH after DSP-4 administration. This is consistent with the existence of an important dopaminergic projection from the substantia nigra to the IC. In conclusion, our study demonstrates and quantifies the noradrenergic projection from the LC to the IC and its subdivisions. The re-examination of the TH and DBH immunoreactivity after DSP-4 treatment provides insights into the source, extent, and topographic distribution of the LC efferent network in the IC, and hence, contributes to our understanding of the role of the noradrenaline (NA) system in auditory processing.Spanish Ministry of Science and Innovation (MICINN)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)AUIP (Programa de Becas de Movilidad Academica)Univ Salamanca, INCYL, Salamanca 37007, SpainUniv Salamanca, Inst Biomed Res Salamanca, Salamanca 37007, SpainSão Paulo State Univ UNESP, Biosci Inst, São Paulo, BrazilUniv Salamanca, Dept Cellular Biol & Pathol, Salamanca 37007, SpainSão Paulo State Univ UNESP, Biosci Inst, São Paulo, BrazilMICINN: BFU2010-17754FAPESP: 08/02771-6Frontiers Research FoundationUniv SalamancaUniversidade Estadual Paulista (Unesp)Hormigo, Sebastiande Castro e Horta Junior, Jose de Anchieta [UNESP]Gomez-Nieto, RicardoLopez, Dolores E.2014-05-20T15:34:09Z2014-05-20T15:34:09Z2012-06-28info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article14application/pdfhttp://dx.doi.org/10.3389/fncir.2012.00041Frontiers In Neural Circuits. Lausanne: Frontiers Research Foundation, v. 6, p. 14, 2012.1662-5110http://hdl.handle.net/11449/4244110.3389/fncir.2012.00041WOS:000305800800001WOS000305800800001.pdfWeb of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengFrontiers In Neural Circuits3.1312,175info:eu-repo/semantics/openAccess2024-01-14T06:19:10Zoai:repositorio.unesp.br:11449/42441Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-01-14T06:19:10Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
The selective neurotoxin DSP-4 impairs the noradrenergic projections from the locus coeruleus to the inferior colliculus in rats |
title |
The selective neurotoxin DSP-4 impairs the noradrenergic projections from the locus coeruleus to the inferior colliculus in rats |
spellingShingle |
The selective neurotoxin DSP-4 impairs the noradrenergic projections from the locus coeruleus to the inferior colliculus in rats Hormigo, Sebastian biotinylated dextran amine dopamine beta hydroxylase deficiency immunohistochemistry densitometry neurotoxicity noradrenergic efferents noradrenergic modulation tyrosine hydroxylase |
title_short |
The selective neurotoxin DSP-4 impairs the noradrenergic projections from the locus coeruleus to the inferior colliculus in rats |
title_full |
The selective neurotoxin DSP-4 impairs the noradrenergic projections from the locus coeruleus to the inferior colliculus in rats |
title_fullStr |
The selective neurotoxin DSP-4 impairs the noradrenergic projections from the locus coeruleus to the inferior colliculus in rats |
title_full_unstemmed |
The selective neurotoxin DSP-4 impairs the noradrenergic projections from the locus coeruleus to the inferior colliculus in rats |
title_sort |
The selective neurotoxin DSP-4 impairs the noradrenergic projections from the locus coeruleus to the inferior colliculus in rats |
author |
Hormigo, Sebastian |
author_facet |
Hormigo, Sebastian de Castro e Horta Junior, Jose de Anchieta [UNESP] Gomez-Nieto, Ricardo Lopez, Dolores E. |
author_role |
author |
author2 |
de Castro e Horta Junior, Jose de Anchieta [UNESP] Gomez-Nieto, Ricardo Lopez, Dolores E. |
author2_role |
author author author |
dc.contributor.none.fl_str_mv |
Univ Salamanca Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Hormigo, Sebastian de Castro e Horta Junior, Jose de Anchieta [UNESP] Gomez-Nieto, Ricardo Lopez, Dolores E. |
dc.subject.por.fl_str_mv |
biotinylated dextran amine dopamine beta hydroxylase deficiency immunohistochemistry densitometry neurotoxicity noradrenergic efferents noradrenergic modulation tyrosine hydroxylase |
topic |
biotinylated dextran amine dopamine beta hydroxylase deficiency immunohistochemistry densitometry neurotoxicity noradrenergic efferents noradrenergic modulation tyrosine hydroxylase |
description |
The inferior colliculus (IC) and the locus coeruleus (LC) are two midbrain nuclei that integrate multimodal information and play a major role in novelty detection to elicit an orienting response. Despite the reciprocal connections between these two structures, the projection pattern and target areas of the LC within the subdivisions of the rat IC are still unknown. Here, we used tract-tracing approaches combined with immunohistochemistry, densitometry, and confocal microscopy (CM) analysis to describe a projection from the LC to the IC. Biotinylated dextran amine (BDA) injections into the LC showed that the LC-IC projection is mainly ipsilateral (90%) and reaches, to a major extent, the dorsal and lateral part of the IC and the intercollicular commissure. Additionally, some LC fibers extend into the central nucleus of the IC. The neurochemical nature of this projection is noradrenergic, given that tyrosine hydroxylase (TH) and dopamine beta hydroxylase (DBH) colocalize with the BDA-Iabeled fibers from the LC. To determine the total field of the LC innervations in the IC, we destroyed the LC neurons and fibers using a highly selective neurotoxin, DSP-4, and then studied the distribution and density of TH- and DBH-immunolabeled axons in the IC. In the DSP-4 treated animals, the number of axonal fibers immunolabeled for TH and DBH were deeply decreased throughout the entire rostrocaudal extent of the IC and its subdivisions compared to controls. Our densitometry results showed that the IC receives up to 97% of its noradrenergic innervations from the LC neurons and only 3% from non-coeruleus neurons. Our results also indicate that TH immunoreactivity in the IC was less impaired than the immunoreactivity for DBH after DSP-4 administration. This is consistent with the existence of an important dopaminergic projection from the substantia nigra to the IC. In conclusion, our study demonstrates and quantifies the noradrenergic projection from the LC to the IC and its subdivisions. The re-examination of the TH and DBH immunoreactivity after DSP-4 treatment provides insights into the source, extent, and topographic distribution of the LC efferent network in the IC, and hence, contributes to our understanding of the role of the noradrenaline (NA) system in auditory processing. |
publishDate |
2012 |
dc.date.none.fl_str_mv |
2012-06-28 2014-05-20T15:34:09Z 2014-05-20T15:34:09Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.3389/fncir.2012.00041 Frontiers In Neural Circuits. Lausanne: Frontiers Research Foundation, v. 6, p. 14, 2012. 1662-5110 http://hdl.handle.net/11449/42441 10.3389/fncir.2012.00041 WOS:000305800800001 WOS000305800800001.pdf |
url |
http://dx.doi.org/10.3389/fncir.2012.00041 http://hdl.handle.net/11449/42441 |
identifier_str_mv |
Frontiers In Neural Circuits. Lausanne: Frontiers Research Foundation, v. 6, p. 14, 2012. 1662-5110 10.3389/fncir.2012.00041 WOS:000305800800001 WOS000305800800001.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Frontiers In Neural Circuits 3.131 2,175 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
14 application/pdf |
dc.publisher.none.fl_str_mv |
Frontiers Research Foundation |
publisher.none.fl_str_mv |
Frontiers Research Foundation |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
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1803650252669976576 |