Plasticity of synaptopodin and the spine apparatus in cortical neurons
Final Report Abstract
The ability of telencephalic neurons to undergo synaptic plasticity is the cellular basis for learning and memory. Studies leading to this proposal have shown that the actinbinding molecule Synaptopodin (SP) plays an important role in this context. It is required for the formation of the spine apparatus organelle, a putative intracellular Ca2+ store, and regulates Ca2+ store-dependent glutamate-receptor (GluA1) trafficking in spines. We have generated SP-transgenic mice, which express GFP-SP or CFP-SP in neurons under the Thy1.2-promoter. During the funding period we crossed these mice with SP-deficient mice and generated animals which only express the transgenic SP but not the endogenous protein. These mice were used to study the function of SP in synaptic plasticity in vitro and in vivo using a combination of genetic, pharmacological, imaging and molecular biological approaches. In a first set of experiments GFP-SP transgenic mice were used to generate organotypic slice cultures of the entorhinal cortex and the hippocampus and employed to study the role of SP in synaptic plasticity. Since a role for SP in GluA1 trafficking had already been described, we wondered whether SP could also be involved in another form of plasticity requiring insertion of GluA1-subunits, i.e. homeostatic synaptic plasticity. We could show that this form of plasticity is induced in hippocampal granule cells following removal of their entorhinal afferents and that changes in synaptic strength inversely correlate with the number of dendritic spines of these cells. The induction of homeostatic synaptic plasticity required SP/spine apparatus since SP-deficient mice did not show this form of plasticity. By crossing SP-deficient mice with the GFP-SP transgenic mice we could rescue this deficit. In a second series of experiments we studied the role of SP/spine apparatus in adult animals. In these studies a role of SP/spine apparatus in synaptic function was suggested. These studies are currently ongoing. In a third set of experiments (collaboration project with Dr. McKinney, Montreal), we found evidence for a role of SP in structural spine plasticity and the formation of spine head protrusions. These studies are ongoing and hold the promise to better understand the molecular players involved in functional and structural plasticity of spines and excitatory synapses in the central nervous system.
Publications
- (2012) Entorhinal denervation induces homeostatic synaptic scaling of excitatory postsynapses of dentate granule cells in mouse organotypic slice cultures. Plos One 7: e32883
Vlachos A, Becker D, Jedlicka P, Winkels R, Roeper J, Deller T
(See online at https://doi.org/10.1371/journal.pone.0032883) - (2012) Functional and Structural properties of dentate granule cells with hilar basal dendrites in mouse entorhino-hippocampal slice cultures. Plos one (11) e48500
Becker D, Willems L, Vnencak M, Zahn N, Schuldt G, Jedlicka P, Maggio N, Deller T, Vlachos A
(See online at https://doi.org/10.1371/journal.pone.0048500) - (2012) Homeostatic Regulation of Gephyrin Scaffolds and Synaptic Strength at Mature Hippocampal GABAergic Postsynapses. Cereb Cortex Aug 23 [Epub ahead of print]
Vlachos A, Reddy-Alla S, Papadopoulos T, Deller T, Betz H
(See online at https://doi.org/10.1093/cercor/bhs260) - (2012) SpineLab: tool for three-dimensional reconstruction of neuronal cell morphology. J Biomed Opt 17: 076007
Jungblut D, Vlachos A, Schuldt G, Zahn N, Deller T, Wittum G
(See online at https://doi.org/10.1117/1.JBO.17.7.076007) - (2012) Time-lapse imaging of granule cells in mouse entorhino-hippocampal slice cultures reveals changes in spine stability after entorhinal denervation. J Comp Neurol 520: 1891-902
Vlachos A, Orth CB, Schneider G, Deller T
(See online at https://doi.org/10.1002/cne.23017)
