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Homer1 gene products orchestrate Ca(2+)-permeable AMPA receptor distribution and LTP expression

We studied the role of Homer1 gene products on the presence of synaptic Ca(2+)-permeable AMPA receptors (AMPARs) and long-term potentiation (LTP) generation in hippocampal CA1 pyramidal neurons, using mice either lacking all Homer1 isoforms (Homer1 KO) or overexpressing the immediate early gene (IEG...

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Autores principales: Rozov, Andrei, Zivkovic, Aleksandar R., Schwarz, Martin K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3489244/
https://www.ncbi.nlm.nih.gov/pubmed/23133416
http://dx.doi.org/10.3389/fnsyn.2012.00004
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author Rozov, Andrei
Zivkovic, Aleksandar R.
Schwarz, Martin K.
author_facet Rozov, Andrei
Zivkovic, Aleksandar R.
Schwarz, Martin K.
author_sort Rozov, Andrei
collection PubMed
description We studied the role of Homer1 gene products on the presence of synaptic Ca(2+)-permeable AMPA receptors (AMPARs) and long-term potentiation (LTP) generation in hippocampal CA1 pyramidal neurons, using mice either lacking all Homer1 isoforms (Homer1 KO) or overexpressing the immediate early gene (IEG) product Homer1a (H1aTG). We found that Homer1 KO caused a significant redistribution of the AMPAR subunit GluA2 from the dendritic compartment to the soma. Furthermore, deletion of Homer1 enhanced the AMPAR-mediated component of glutamatergic currents at Schaffer collateral synapses as demonstrated by increased AMPA/NMDA current ratios. Meanwhile, LTP generation appeared to be unaffected. Conversely, sustained overexpression of Homer1a strongly reduced AMPA/NMDA current ratios and polyamine sensitivity of synaptic AMPAR, indicating that the proportion of synaptic GluA2-containing AMPAR increased relative to WT. LTP maintenance was abolished in H1aTG. Notably, overexpression of Homer1a in Homer1 KO or GluA2 KO mice did not affect LTP expression, suggesting activity-dependent interaction between Homer1a and long Homer1 isoforms with GluA2-containing AMPAR. Thus, Homer1a is essential for the activity-dependent regulation of excitatory synaptic transmission.
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spelling pubmed-34892442012-11-06 Homer1 gene products orchestrate Ca(2+)-permeable AMPA receptor distribution and LTP expression Rozov, Andrei Zivkovic, Aleksandar R. Schwarz, Martin K. Front Synaptic Neurosci Neuroscience We studied the role of Homer1 gene products on the presence of synaptic Ca(2+)-permeable AMPA receptors (AMPARs) and long-term potentiation (LTP) generation in hippocampal CA1 pyramidal neurons, using mice either lacking all Homer1 isoforms (Homer1 KO) or overexpressing the immediate early gene (IEG) product Homer1a (H1aTG). We found that Homer1 KO caused a significant redistribution of the AMPAR subunit GluA2 from the dendritic compartment to the soma. Furthermore, deletion of Homer1 enhanced the AMPAR-mediated component of glutamatergic currents at Schaffer collateral synapses as demonstrated by increased AMPA/NMDA current ratios. Meanwhile, LTP generation appeared to be unaffected. Conversely, sustained overexpression of Homer1a strongly reduced AMPA/NMDA current ratios and polyamine sensitivity of synaptic AMPAR, indicating that the proportion of synaptic GluA2-containing AMPAR increased relative to WT. LTP maintenance was abolished in H1aTG. Notably, overexpression of Homer1a in Homer1 KO or GluA2 KO mice did not affect LTP expression, suggesting activity-dependent interaction between Homer1a and long Homer1 isoforms with GluA2-containing AMPAR. Thus, Homer1a is essential for the activity-dependent regulation of excitatory synaptic transmission. Frontiers Media S.A. 2012-09-27 /pmc/articles/PMC3489244/ /pubmed/23133416 http://dx.doi.org/10.3389/fnsyn.2012.00004 Text en Copyright © 2012 Rozov, Zivkovic and Schwarz. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
spellingShingle Neuroscience
Rozov, Andrei
Zivkovic, Aleksandar R.
Schwarz, Martin K.
Homer1 gene products orchestrate Ca(2+)-permeable AMPA receptor distribution and LTP expression
title Homer1 gene products orchestrate Ca(2+)-permeable AMPA receptor distribution and LTP expression
title_full Homer1 gene products orchestrate Ca(2+)-permeable AMPA receptor distribution and LTP expression
title_fullStr Homer1 gene products orchestrate Ca(2+)-permeable AMPA receptor distribution and LTP expression
title_full_unstemmed Homer1 gene products orchestrate Ca(2+)-permeable AMPA receptor distribution and LTP expression
title_short Homer1 gene products orchestrate Ca(2+)-permeable AMPA receptor distribution and LTP expression
title_sort homer1 gene products orchestrate ca(2+)-permeable ampa receptor distribution and ltp expression
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3489244/
https://www.ncbi.nlm.nih.gov/pubmed/23133416
http://dx.doi.org/10.3389/fnsyn.2012.00004
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