The role of synaptopodin, the spine apparatus and the axonal cisternal organelle in activity-dependent synaptic and network plasticity in the dentate gyrus

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Learning and memory formation are accompanied by changes of synaptic strength (plasticity) in the hippocampus. Synaptopodin is an actin-associated protein that is located at both the spine apparatuses of dendritic spines (targets of synaptic excitation) and the cisternal organelles of axon initial segments (targets of GABAergic synaptic inhibition) in hippocampal neurons. Activity-dependent changes in the actin cytoskeleton and its associated proteins, including synaptopodin, play a crucial role in structural synaptic plasticity in hippocampal neurons (Fukazawa et al. 2003, Ouyang et al. 2005). Synaptopodin-deficient mice lack spine apparatuses and cisternal organelles (Deller et al. 2003; Bas Orth et al., unpublished). We plan to study short-term plasticity, long-term plasticity (LTP) and recurrent inhibition in wildtype and synaptopodin-deficient mice on hippocampal granule cells following stimulation of their main afferent input (perforant-path), under in vivo and in vitro conditions. Whereas an impaired LTP may be associated with the lack of dendritic spine apparatuses, an altered recurrent inhibition might be related to the lack of cisternal organelles at axon initial segment. Structural changes will be studied histologically with markers for the cisternal organelle (synaptopodin), the axon initial segment (ß-IV-spectrin), and GABA and GABAA receptors. We will use a computational model to analyse the balance of hippocampal inhibition and excitation. Our work will lead to a better understanding of the structural changes underlying synaptic plasticity in the hippocampus.