Ann Anat 189 (2007) 5—16 A role for synaptopodin and the spine apparatus in hippocampal synaptic plasticity $ Thomas Deller a,Ã , Carlos Bas Orth a , Domenico Del Turco a , Andreas Vlachos a , Guido J. Burbach a , Alexander Drakew b , Sophie Chabanis c , Martin Korte d , Herbert Schwegler e , Carola A. Haas f , Michael Frotscher b a Institute of Clinical Neuroanatomy, J. W. Goethe-University, Theodor-Stern-Kai 7, D-60590 Frankfurt/Main, Germany b Institute of Anatomy and Cell Biology, Albert Ludwigs-University, P. O. Box 111, D-79001, Freiburg, Germany c Structural and Computational Biology Unit, European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany d Institute of Zoology, Mendelssohnstraße 4, Technical University Braunschweig, D-38106, Braunschweig, Germany e Institute of Anatomy, University of Magdeburg, Leipzigerstr. 44, D-39120 Magdeburg, Germany f Department of Neurosurgery, Albert Ludwigs-University, P. O. Box 111, D-79001 Freiburg, Germany Received 6 June 2006; accepted 19 June 2006 KEYWORDS Dendritic plasticity; Cytoskeleton; Actin; Calcium stores; Excitatory synapse Summary Spines are considered sites of synaptic plasticity in the brain and are capable of remodeling their shape and size. A molecule that has been implicated in spine plasticity is the actin-associated protein synaptopodin. This article will review a series of studies aimed at elucidating the role of synaptopodin in the rodent brain. First, the developmental expression of synaptopodin mRNA and protein were studied; secondly, the subcellular localization of synaptopodin in hippocampal principal neurons was analyzed using confocal microscopy as well as electron microscopy and immunogold labelling; and, finally, the functional role of synaptopodin was investigated using a synaptopodin-deficient mouse. The results of these studies are: (1) synaptopodin expression by hippocampal principal neurons develops during the first postnatal weeks and increases in parallel with the maturation of spines in the hippocampus. (2) Synaptopodin is sorted to the spine compartment, where it is tightly associated with the spine apparatus, an enigmatic organelle believed to be involved in calcium storage or local protein synthesis. (3) Synaptopodin-deficient mice generated by gene targeting are viable but lack the spine apparatus organelle. These mice show deficits in synaptic plasticity as well as impaired learning and memory. Taken together, these data implicate synaptopodin ARTICLE IN PRESS www.elsevier.de/aanat 0940-9602/$ - see front matter & 2006 Elsevier GmbH. All rights reserved. doi:10.1016/j.aanat.2006.06.013 $ Lecture at the 101st meeting of the Anatomische Gesellschaft in Freiburg, April 7–10, 2006. Ã Corresponding author. Tel.: +49 69 6301 6361; fax: +49 69 6301 6425. E-mail address: T.Deller@em.uni-frankfurt.de (T. Deller).