Eine neue Rolle für Synaptopodin bei Lernvorgängen im Gehirn: aktivitätsabhängige somatische Expression von Synaptopodin in Körnerzellen des Gyrus dentatus nach Explorationsverhalten
Zusammenfassung der Projektergebnisse
The actin-modulating protein Synaptopodin (SP) plays an important role in neuronal plasticity processes. In earlier work, we have focused on the role of SP in spines and the axon initial segment and could show that SP is an essential component of two cellular organelles associated with the endoplasmic reticulum (ER), i.e. the spine apparatus and the cisternal organelle of the axon initial segment. We now discovered a third cellular location for SP in the somata of granule cells (GC) in the dentate gyrus and, again, found SP tightly associated with ER ("somatic SP"). Within the dentate gyrus, somatic SP was selectively expressed by a subpopulation of Arc-positive GCs. Work by others has shown that these Arc-positive GCs are connected, form a so-called "ensemble", and form representations of the environment of the mouse in its brain. We, therefore, proposed to study (1) whether SP is induced in GC ensembles in a novel environment, (2) whether SP is essential for the stacking of somatic cisterns, and (3) whether SP upregulation in the activated GCs affects other SP-containing compartments. Using a combination of genetic, high-end imaging, electrophysiology, and cell biology techniques we could show that (1) SP is robustly induced within 2 hours in activated ensemble cells and co-localizes with Arc and alpha-actinin-2. This induction depends on an intact entorhino-hippocampal pathway. (2) SP is required for the stacking of somatic cisterns, since SP-deficient mice do not form ER stacks in Arcpositive ensembles. (3) Somatic SP-positive neurons strongly upregulated SP mRNA and protein. Accordingly, we investigated the effects of an upregulation of SP in GCs overexpressing the protein. This revealed that higher levels of SP result in more SP-positive spines, more active synapses, and more stable spines. We are now proposing a working model: Behaviorally activated GCs upregulate SP mRNA and protein. This results in changes in the soma and in the dendrites. In the soma, SP reorganizes the ER into stacks, which may modify calcium signaling from the synapse to the nucleus. In the dendrites, the number of SP-positive spines is increased, which may make the GCs more plastic and may promote their integration into new context-specific ensembles. During the funding period, we generated all necessary tools, i.e. developed a method to induce somatic SP-cisterns in vitro, generated a tool-box of SP-deletion constructs, established high-resolution calcium imaging, to test our working model in a renewal project.
Projektbezogene Publikationen (Auswahl)
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Granule Cell Ensembles in Mouse Dentate Gyrus Rapidly Upregulate the Plasticity-Related Protein Synaptopodin after Exploration Behavior. Cerebral Cortex, 30(4), 2185-2198.
Paul, Mandy H.; Choi, Myoung; Schlaudraff, Jessica; Deller, Thomas & Del, Turco Domenico
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The actin-modulating protein synaptopodin mediates long-term survival of dendritic spines. eLife, 9.
Yap, Kenrick; Drakew, Alexander; Smilovic, Dinko; Rietsche, Michael; Paul, Mandy H.; Vuksic, Mario; Del Turco, Domenico & Deller, Thomas
