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BDNF–TrkB signaling in striatopallidal neurons controls inhibition of locomotor behavior

The physiology of brain-derived neurotrophic factor signaling in enkephalinergic striatopallidal neurons is poorly understood. Changes in cortical Bdnf expression levels, and/or impairment in brain-derived neurotrophic factor anterograde transport induced by mutant huntingtin (mHdh) are believed to...

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Autores principales: Besusso, Dario, Geibel, Mirjam, Kramer, Dana, Schneider, Tomasz, Pendolino, Valentina, Picconi, Barbara, Calabresi, Paolo, Bannerman, David M., Minichiello, Liliana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Pub. Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3940866/
https://www.ncbi.nlm.nih.gov/pubmed/23774276
http://dx.doi.org/10.1038/ncomms3031
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author Besusso, Dario
Geibel, Mirjam
Kramer, Dana
Schneider, Tomasz
Pendolino, Valentina
Picconi, Barbara
Calabresi, Paolo
Bannerman, David M.
Minichiello, Liliana
author_facet Besusso, Dario
Geibel, Mirjam
Kramer, Dana
Schneider, Tomasz
Pendolino, Valentina
Picconi, Barbara
Calabresi, Paolo
Bannerman, David M.
Minichiello, Liliana
author_sort Besusso, Dario
collection PubMed
description The physiology of brain-derived neurotrophic factor signaling in enkephalinergic striatopallidal neurons is poorly understood. Changes in cortical Bdnf expression levels, and/or impairment in brain-derived neurotrophic factor anterograde transport induced by mutant huntingtin (mHdh) are believed to cause striatopallidal neuron vulnerability in early-stage Huntington’s disease. Although several studies have confirmed a link between altered cortical brain-derived neurotrophic factor signaling and striatal vulnerability, it is not known whether the effects are mediated via the brain-derived neurotrophic factor receptor TrkB, and whether they are direct or indirect. Using a novel genetic mouse model, here, we show that selective removal of brain-derived neurotrophic factor–TrkB signaling from enkephalinergic striatal targets unexpectedly leads to spontaneous and drug-induced hyperlocomotion. This is associated with dopamine D2 receptor-dependent increased striatal protein kinase C and MAP kinase activation, resulting in altered intrinsic activation of striatal enkephalinergic neurons. Therefore, brain-derived neurotrophic factor/TrkB signaling in striatopallidal neurons controls inhibition of locomotor behavior by modulating neuronal activity in response to excitatory input through the protein kinase C/MAP kinase pathway.
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spelling pubmed-39408662014-03-04 BDNF–TrkB signaling in striatopallidal neurons controls inhibition of locomotor behavior Besusso, Dario Geibel, Mirjam Kramer, Dana Schneider, Tomasz Pendolino, Valentina Picconi, Barbara Calabresi, Paolo Bannerman, David M. Minichiello, Liliana Nat Commun Article The physiology of brain-derived neurotrophic factor signaling in enkephalinergic striatopallidal neurons is poorly understood. Changes in cortical Bdnf expression levels, and/or impairment in brain-derived neurotrophic factor anterograde transport induced by mutant huntingtin (mHdh) are believed to cause striatopallidal neuron vulnerability in early-stage Huntington’s disease. Although several studies have confirmed a link between altered cortical brain-derived neurotrophic factor signaling and striatal vulnerability, it is not known whether the effects are mediated via the brain-derived neurotrophic factor receptor TrkB, and whether they are direct or indirect. Using a novel genetic mouse model, here, we show that selective removal of brain-derived neurotrophic factor–TrkB signaling from enkephalinergic striatal targets unexpectedly leads to spontaneous and drug-induced hyperlocomotion. This is associated with dopamine D2 receptor-dependent increased striatal protein kinase C and MAP kinase activation, resulting in altered intrinsic activation of striatal enkephalinergic neurons. Therefore, brain-derived neurotrophic factor/TrkB signaling in striatopallidal neurons controls inhibition of locomotor behavior by modulating neuronal activity in response to excitatory input through the protein kinase C/MAP kinase pathway. Nature Pub. Group 2013-06-18 /pmc/articles/PMC3940866/ /pubmed/23774276 http://dx.doi.org/10.1038/ncomms3031 Text en Copyright © 2013, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/3.0/ This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. To view a copy of this licence visit http://creativecommons.org/licenses/by/3.0/.
spellingShingle Article
Besusso, Dario
Geibel, Mirjam
Kramer, Dana
Schneider, Tomasz
Pendolino, Valentina
Picconi, Barbara
Calabresi, Paolo
Bannerman, David M.
Minichiello, Liliana
BDNF–TrkB signaling in striatopallidal neurons controls inhibition of locomotor behavior
title BDNF–TrkB signaling in striatopallidal neurons controls inhibition of locomotor behavior
title_full BDNF–TrkB signaling in striatopallidal neurons controls inhibition of locomotor behavior
title_fullStr BDNF–TrkB signaling in striatopallidal neurons controls inhibition of locomotor behavior
title_full_unstemmed BDNF–TrkB signaling in striatopallidal neurons controls inhibition of locomotor behavior
title_short BDNF–TrkB signaling in striatopallidal neurons controls inhibition of locomotor behavior
title_sort bdnf–trkb signaling in striatopallidal neurons controls inhibition of locomotor behavior
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3940866/
https://www.ncbi.nlm.nih.gov/pubmed/23774276
http://dx.doi.org/10.1038/ncomms3031
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