Correlated plasticity of synaptic structures and its relationship to the stabilization of synaptic enlargement

摘要: The ability to adapt environmental changes, learn and memorize information is one of the brain’s most extraordinary features. One important process underlying this considered be synaptic plasticity, i.e. the structural functional modification connections. Synaptic plasticity can occur either by genesis or elimination connections, at existing connections modifications in strength transmission. Synaptic connections are complex entities consisting different functional structures: majority hippocampal cortical excitatory synapses are made up a postsynaptic compartment called dendritic spine presynaptic compartment bouton. Within bouton dense molecular structures, which serve transmission between pre‐ postsynapse, exist, namely density (PSD) spine, active zone (AZ) in All these structures correlated size with synaptic strength. function correlation serves efficient fast transmission neuronal signals. During coordinated change in all expected, for maintenance their correlation. However, date, such have not been examined detail. Furthermore, mechanisms of structural changes after plasticity remain poorly understood. aim thesis was explore questions. To achieve this I carried out two complementing experimental approaches: In first set experiments, I studied PSD twophoton time‐lapse imaging two synaptic structures. induce structural stimulated single dendritic spines Schaffer collateral cultured slices by two‐photon glutamate uncaging. This shown previously accompanied by an increase strength. visualize plasticity of their PSD, cytosolic marker tdTomato EGFP‐tagged structural proteins PSD‐95 Homer1c, were co‐expressed. PSD‐95 Homer1c important abundant scaffolding the PSD, been used as markers size. found that both PSD‐95 levels increased stimulation. increased rather rapidly whereas did so delayed manner relative increase in volume. Thus, naive protein level spine volume only transiently disrupted induction, but was reestablished over time course 3 hours. only increased significantly persistent enlargement, spines with non‐persistent enlargement. On other hand, initially increased both without then decayed back original Because the delayed, investigated whether application of PKA activator forskolin, supports persistent enlargement uncaging, might promote therefore accelerate level. experiments led to unexpected results: forskolin application neither had effect on volume nor increase. Although scaffolding proteins, they represent multitude form the PSD. Consequently, does necessarily represent whole. Therefore, second experimental approach, applied electron microscopy displayed a stable enlargement hours Hereby, able to reconstruct entire also stimulated spine: matching dimensions hours after stimulation, similar naive, unstimulated spines. In summary, combining two‐photon uncaging time‐lapse imaging microscopy, bouton increase during these structures reestablished stimulation scale hours. Furthermore, correlates stabilization of plasticity. suggests model where the balancing hallmark stabilization structural modifications