We have made substantial progress towards characterising and unlocking the functional significance of synapse diversity in the mammalian brain. A key finding in the context of learning and memory is that synaptome maps can be used as a mechanism for storing information. Disease mutations, such as those seen in schizophrenia and autism, alter these maps, potentially affecting information storage/recall and how the external world is represented. Olanzapine, a commonly prescribed antipsychotic medication, can also change the synaptome maps, opening up opportunities of using synaptome mapping for drug development to treat brain disease. A second key finding is that synaptome maps are not fixed even in normal life, but change (‘plasticity’) throughout the lifespan (see figure) and in a characteristic way that mirrors natural changes in cognitive ability during development and ageing. These lifespan changes may also help to explain why we are susceptible to certain brain disorders at particular ages. A third key finding is that synaptome maps may help us to understood how and where memories of different durations are stored and why this capacity changes throughout life and in brain diseases. The synapse protein PSD95, which is required to write and store memories, seems to last longest in synapse types found in areas of the brain that store long-term memories. Sleep deprivation causes a decrease in short-protein-lifetime synapses, consistent with its effect on short-term memory. The schizophrenia mutation alters how long PSD95 lasts, which might contribute to the cognitive dysfunction of this condition. All the data that we have gathered during the project have been made freely available to the research community through online databases, together with tools that facilitate data discovery and analysis in order to maximise the reuse and potential health impact of our data.
