A novel role for Synaptopodin in learning and memory: somatic expression of Synaptopodin in dentate granule cells activated by exploration behavior

• Applicants: Domenico Del Turco, Ph.D.; Professor Dr. Thomas Deller
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2016 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 324940093

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, i.e. spine apparatus and cisternal organelle. We now discovered an activity-dependent third cellular location for SP in the somata of granule cells activated by exploration behavior. Preliminary investigations have revealed that this somatic expression of SP is associated with somatic ER-cisterns and that most of the granule cells expressing somatic SP also express Arc. Similar to Arc, the number of SP-positive cells in the mouse dentate gyrus increased after behavioral exploration in a novel environment. These preliminary data link SP to the fast activation of granule cells in novel environments and the formation of environmental representations in this brain region.Using a combination of methods from genetics, electrophysiology, and cell biology, we will study the role of somatic SP in the dentate gyrus and will address the following questions: (1) Which cellular structures and IEGs are associated with somatic SP? (2) How is SP sorted into the somatic subcompartment? (3) Which signals induce somatic SP in granule cells? (4) What is the functional role of SP in the soma? (5) What is the relevance of somatic SP for exploration behavior? Our studies will provide new insights into the unexpected and novel biological role of SP in the encoding of different environments in the mature CNS.

• DFG Programme: Research Grants