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Muskelin regulates actin-dependent synaptic changes and intrinsic brain activity relevant to behavioral and cognitive processes

Muskelin (Mkln1) is implicated in neuronal function, regulating plasma membrane receptor trafficking. However, its influence on intrinsic brain activity and corresponding behavioral processes remains unclear. Here we show that murine Mkln1 knockout causes non-habituating locomotor activity, increase...

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Autores principales: Muhia, Mary, YuanXiang, PingAn, Sedlacik, Jan, Schwarz, Jürgen R., Heisler, Frank F., Gromova, Kira V., Thies, Edda, Breiden, Petra, Pechmann, Yvonne, Kreutz, Michael R., Kneussel, Matthias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9200775/
https://www.ncbi.nlm.nih.gov/pubmed/35705737
http://dx.doi.org/10.1038/s42003-022-03446-1
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author Muhia, Mary
YuanXiang, PingAn
Sedlacik, Jan
Schwarz, Jürgen R.
Heisler, Frank F.
Gromova, Kira V.
Thies, Edda
Breiden, Petra
Pechmann, Yvonne
Kreutz, Michael R.
Kneussel, Matthias
author_facet Muhia, Mary
YuanXiang, PingAn
Sedlacik, Jan
Schwarz, Jürgen R.
Heisler, Frank F.
Gromova, Kira V.
Thies, Edda
Breiden, Petra
Pechmann, Yvonne
Kreutz, Michael R.
Kneussel, Matthias
author_sort Muhia, Mary
collection PubMed
description Muskelin (Mkln1) is implicated in neuronal function, regulating plasma membrane receptor trafficking. However, its influence on intrinsic brain activity and corresponding behavioral processes remains unclear. Here we show that murine Mkln1 knockout causes non-habituating locomotor activity, increased exploratory drive, and decreased locomotor response to amphetamine. Muskelin deficiency impairs social novelty detection while promoting the retention of spatial reference memory and fear extinction recall. This is strongly mirrored in either weaker or stronger resting-state functional connectivity between critical circuits mediating locomotor exploration and cognition. We show that Mkln1 deletion alters dendrite branching and spine structure, coinciding with enhanced AMPAR-mediated synaptic transmission but selective impairment in synaptic potentiation maintenance. We identify muskelin at excitatory synapses and highlight its role in regulating dendritic spine actin stability. Our findings point to aberrant spine actin modulation and changes in glutamatergic synaptic function as critical mechanisms that contribute to the neurobehavioral phenotype arising from Mkln1 ablation.
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spelling pubmed-92007752022-06-17 Muskelin regulates actin-dependent synaptic changes and intrinsic brain activity relevant to behavioral and cognitive processes Muhia, Mary YuanXiang, PingAn Sedlacik, Jan Schwarz, Jürgen R. Heisler, Frank F. Gromova, Kira V. Thies, Edda Breiden, Petra Pechmann, Yvonne Kreutz, Michael R. Kneussel, Matthias Commun Biol Article Muskelin (Mkln1) is implicated in neuronal function, regulating plasma membrane receptor trafficking. However, its influence on intrinsic brain activity and corresponding behavioral processes remains unclear. Here we show that murine Mkln1 knockout causes non-habituating locomotor activity, increased exploratory drive, and decreased locomotor response to amphetamine. Muskelin deficiency impairs social novelty detection while promoting the retention of spatial reference memory and fear extinction recall. This is strongly mirrored in either weaker or stronger resting-state functional connectivity between critical circuits mediating locomotor exploration and cognition. We show that Mkln1 deletion alters dendrite branching and spine structure, coinciding with enhanced AMPAR-mediated synaptic transmission but selective impairment in synaptic potentiation maintenance. We identify muskelin at excitatory synapses and highlight its role in regulating dendritic spine actin stability. Our findings point to aberrant spine actin modulation and changes in glutamatergic synaptic function as critical mechanisms that contribute to the neurobehavioral phenotype arising from Mkln1 ablation. Nature Publishing Group UK 2022-06-15 /pmc/articles/PMC9200775/ /pubmed/35705737 http://dx.doi.org/10.1038/s42003-022-03446-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Muhia, Mary
YuanXiang, PingAn
Sedlacik, Jan
Schwarz, Jürgen R.
Heisler, Frank F.
Gromova, Kira V.
Thies, Edda
Breiden, Petra
Pechmann, Yvonne
Kreutz, Michael R.
Kneussel, Matthias
Muskelin regulates actin-dependent synaptic changes and intrinsic brain activity relevant to behavioral and cognitive processes
title Muskelin regulates actin-dependent synaptic changes and intrinsic brain activity relevant to behavioral and cognitive processes
title_full Muskelin regulates actin-dependent synaptic changes and intrinsic brain activity relevant to behavioral and cognitive processes
title_fullStr Muskelin regulates actin-dependent synaptic changes and intrinsic brain activity relevant to behavioral and cognitive processes
title_full_unstemmed Muskelin regulates actin-dependent synaptic changes and intrinsic brain activity relevant to behavioral and cognitive processes
title_short Muskelin regulates actin-dependent synaptic changes and intrinsic brain activity relevant to behavioral and cognitive processes
title_sort muskelin regulates actin-dependent synaptic changes and intrinsic brain activity relevant to behavioral and cognitive processes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9200775/
https://www.ncbi.nlm.nih.gov/pubmed/35705737
http://dx.doi.org/10.1038/s42003-022-03446-1
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