title: Homer1 gene products orchestrate Ca(2+)-permeable AMPA receptor distribution and LTP expression.
abstract: 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.
authors.affiliation: IZN and Department of Clinical Neurobiology, University Hospital Heidelberg, Germany ; Division of Neuroscience, Medical Research Institute Ninewells Hospital and Medical School, Dundee University Dundee, UK.
authors.forename: Andrei
authors.initials: A
authors.lastname: Rozov
authors.forename: Aleksandar R
authors.initials: AR
authors.lastname: Zivkovic
authors.forename: Martin K
authors.initials: MK
authors.lastname: Schwarz
keywords: AMPA receptors; LTP; homer; receptor trafficking; transgenic mouse models