Our current research is focussed on uncovering the scope and functional impacts of synapse diversity throughout the brain. We have developed methods for brain-wide mapping of protein composition at single-synapse resolution. These ‘synaptome’ maps, which reveal the molecular and morphological features of a billion synapses, have uncovered unprecedented spatiotemporal synapse diversity organised into an architecture that correlates with the structural and functional connectomes. We have characterised how the synaptome architecture of the brain changes throughout the lifespan, with phases of rapid expansion followed by slow decline in old age that may inform on natural ageing and windows of disease susceptibility. Importantly, we have shown that mutations that cause cognitive disorders such as autism reorganise synaptome maps.

These new findings on synapse diversity have important implications for brain function in terms of learning and memory, leading to new models of how information is stored and recalled. We are now investigating the dynamics of the synaptome – the extent to which synapses change in the short term, during daily sleep cycles, and how rapidly synapse proteins are replaced; and, in the longer term, how sensory inputs from the environment and activity-dependent behaviour influence synaptome development. We are also unlocking brain complexity by characterising synapse diversity in the fundamental unit of the brain – the individual neuron. A major effort is progressing our laboratory, image analysis and computational tools to the direct study of the human brain, revealing the progressive impacts on the synaptome of dysfunctions such as Alzheimer’s disease, schizophrenia and ALS-FTD. Synaptome mapping also has the potential to complement clinical techniques, uncovering what diagnostic imaging approaches such as PET tell us about damage to the synaptome. A key aim going forwards is to integrate all these synaptome data within existing large-scale international brain data resources to maximize their health discovery value.