PSD95 Lifetime Synaptome Atlas of the mouse brain.

Where memories are stored in the brain and how the capacity to learn and remember changes with age are poorly understood. Synapse proteins are necessary for all behaviour and their lifetime may instruct us on how memories are stored in synapses and how diseases cause cognitive and behavioural impairments. We have developed methods to visualise and quantify the lifetime of proteins in individual synapses across the mouse brain and lifespan. We mapped the lifetime of PSD95, a postsynaptic protein required for writing and maintenance of memories, in individual synapses across the brain of young, mature and old mice. Synapses with diverse protein lifetimes form a special architecture in dendrites, circuits and brain regions that changes across the lifespan. The spatiotemporal distribution of synapses with different memory durations may explain normal and pathological features of memory.