Original Research Article
Select overexpression of homer1a in dorsal hippocampus impairs spatial working memory
Tansu Celikel 1, Verena Marx 2, Florian Freudenberg 2, Aleksander Zivkovic 3, Evgeny Resnik 1, Mazahir T. Hasan 4, Pawel Licznerski 2, Pavel Osten 2, Andrej Rozov 3, Peter H. Seeburg 2* and Martin K. Schwarz 2
1 Department of Cell Physiology , Max-Planck-Institute for Medical Research, Germany
2 Department of Molecular Neurobiology, Max-Planck-Institute for Medical Research, Germany
3 IZN and Department of Clinical Neurobiology, University Hospital of Neurology, Germany
4 Department of Biomedical Optics, Max-Planck-Institute for Medical Research, Germany
2 Department of Molecular Neurobiology, Max-Planck-Institute for Medical Research, Germany
3 IZN and Department of Clinical Neurobiology, University Hospital of Neurology, Germany
4 Department of Biomedical Optics, Max-Planck-Institute for Medical Research, Germany
Long Homer proteins forge assemblies of signaling components involved in glutamate receptor signaling in postsynaptic excitatory neurons, including those underlying synaptic transmission and plasticity. The short immediate-early gene (IEG) Homer1a can dynamically uncouple these physical associations by functional competition with long Homer isoforms. To examine the consequences of Homer1amediated "uncoupling" for synaptic plasticity and behavior, we generated forebrain-specific tetracycline (tet) controlled expression of Venus-tagged Homer1a (H1aV) in mice. We report that sustained overexpression of H1aV impaired spatial working but not reference memory. Most notably, a similar impairment was observed when H1aV expression was restricted to the dorsal hippocampus (HP), which identifies this structure as the principal cortical area for spatial working memory. Interestingly, H1aV overexpression also abolished maintenance of CA3-CA1 long-term potentiation (LTP). These impairments, generated by sustained high Homer1a levels, identify a requirement for long Homer forms in synaptic plasticity and temporal encoding of spatial memory.
Keywords: hippocampus, spatial working memory, spatial reference memory, immediate early gene, Homer1a, synaptic plasticity, viral expression
Copyright: © 2007 Celikel, Marx, Freudenberg, Zivkovic, Resnik, Hasan, Licznerski, Osten, Rozov, Seeburg and Schwarz. This is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.
*Correspondence: Peter H. Seeburg, Department of Molecular Neurobiology, Max-Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany. e-mail: seeburg@mpimf-heidelberg.mpg.de
Citation: Celikel T, Marx V, Freudenberg F, Zivkovic A, Resnik E, Hasan MT, Licznerski P, Osten P, Rozov A, Seeburg PH and Schwarz MK (2007) Select overexpression of homer1a in dorsal hippocampus impairs spatial working memory. Front. Neurosci. 1,1:97-110. doi:10.3389/neuro.01.1.1.007.2007
Received: 15 August 2007; paper pending published: 01 September 2007; accepted: 01 September 2007; published online: 15 October 2007.
Edited by:
Henry Markram, Brain Mind Institute, Ecole Polytechnique Fédéral de Lausanne, Switzerland
Reviewed by:
Seth G N . Grant, The Wellcome Trust Sanger Institure, UK
Henry Markram, Brain Mind Institute, Ecole Polytechnique Fédéral de Lausanne, Switzerland
Henry Markram, Brain Mind Institute, Ecole Polytechnique Fédéral de Lausanne, Switzerland
*Correspondence: Peter H. Seeburg, Department of Molecular Neurobiology, Max-Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany. e-mail: seeburg@mpimf-heidelberg.mpg.de
