It is widely believed that memories are encoded and stored in the pattern and strength of synaptic connections. Individual synapses, the elementary units of information transfer, encode and store new information in response to the environmental changes through structural and functional reorganization. The key mechanisms that normally maintain plasticity of synapses and initiate synapse loss in neurodegenerative diseases remain elusive. To target this question, we developed an integrative approach to correlate structure and function at the level of single synapses in hippocampal circuits. Utilizing FRET spectroscopy, optical imaging, electrophysiology and molecular biology we explore the casual relationship between the pattern of ongoing neuronal activity, structural rearrangements within the synaptic signaling complexes and plasticity of single synapses and whole networks. Our results suggest that ongoing background synaptic activity critically determines the number and plasticity of synapses in hippocampal circuits.
