article published yes Mary W Muhia author ab7ed20f-09f7-11eb-909c-d5d0b443ee9d PingAn YuanXiang author Jan Sedlacik author Jürgen R. Schwarz author Frank F. Heisler author Kira V. Gromova author Edda Thies author Petra Breiden author Yvonne Pechmann author Michael R. Kreutz author Matthias Kneussel author PreCl department 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 <jats:italic>Mkln1</jats:italic> 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 <jats:italic>Mkln1</jats:italic> 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 <jats:italic>Mkln1</jats:italic> ablation. https://research-explorer.ista.ac.at/download/12224/12417/2022_CommBiology_Muhia.pdf application/pdfno https://creativecommons.org/licenses/by/4.0/ Springer Nature2022 eng General Agricultural and Biological SciencesGeneral BiochemistryGenetics and Molecular BiologyMedicine (miscellaneous) 2399-3642 00081177790000310.1038/s42003-022-03446-1 5 Muhia, Mary W, PingAn YuanXiang, Jan Sedlacik, Jürgen R. Schwarz, Frank F. Heisler, Kira V. Gromova, Edda Thies, et al. “Muskelin Regulates Actin-Dependent Synaptic Changes and Intrinsic Brain Activity Relevant to Behavioral and Cognitive Processes.” <i>Communications Biology</i>. Springer Nature, 2022. <a href="https://doi.org/10.1038/s42003-022-03446-1">https://doi.org/10.1038/s42003-022-03446-1</a>. Muhia MW, YuanXiang P, Sedlacik J, et al. Muskelin regulates actin-dependent synaptic changes and intrinsic brain activity relevant to behavioral and cognitive processes. <i>Communications Biology</i>. 2022;5. doi:<a href="https://doi.org/10.1038/s42003-022-03446-1">10.1038/s42003-022-03446-1</a> Muhia, Mary W., et al. “Muskelin Regulates Actin-Dependent Synaptic Changes and Intrinsic Brain Activity Relevant to Behavioral and Cognitive Processes.” <i>Communications Biology</i>, vol. 5, 589, Springer Nature, 2022, doi:<a href="https://doi.org/10.1038/s42003-022-03446-1">10.1038/s42003-022-03446-1</a>. Muhia MW, YuanXiang P, Sedlacik J, Schwarz JR, Heisler FF, Gromova KV, Thies E, Breiden P, Pechmann Y, Kreutz MR, Kneussel M. 2022. Muskelin regulates actin-dependent synaptic changes and intrinsic brain activity relevant to behavioral and cognitive processes. Communications Biology. 5, 589. M. W. Muhia <i>et al.</i>, “Muskelin regulates actin-dependent synaptic changes and intrinsic brain activity relevant to behavioral and cognitive processes,” <i>Communications Biology</i>, vol. 5. Springer Nature, 2022. Muhia, M. W., YuanXiang, P., Sedlacik, J., Schwarz, J. R., Heisler, F. F., Gromova, K. V., … Kneussel, M. (2022). Muskelin regulates actin-dependent synaptic changes and intrinsic brain activity relevant to behavioral and cognitive processes. <i>Communications Biology</i>. Springer Nature. <a href="https://doi.org/10.1038/s42003-022-03446-1">https://doi.org/10.1038/s42003-022-03446-1</a> M.W. Muhia, P. YuanXiang, J. Sedlacik, J.R. Schwarz, F.F. Heisler, K.V. Gromova, E. Thies, P. Breiden, Y. Pechmann, M.R. Kreutz, M. Kneussel, Communications Biology 5 (2022). 122242023-01-16T09:48:19Z2024-10-09T21:03:48Z