You are invited to join the UK Dementia Research Institute at Imperial College London for the first instalment of their newly-launched seminar series.
A light lunch will be available from 1pm.
Synaptome mapping: new technical approaches for unravelling the molecular architecture of synapses and the brain
Prof. Seth Grant, FRSE, FMedSci Centre for Clinical Brain Sciences University of Edinburgh
Synapses are hallmarks of brain complexity – they are found in vast numbers and contain over 1,000 protein types. What is the purpose of this molecular complexity, how did it arise, and is there any logic to its organization?
We have addressed these issues using large-scale molecular approaches focused on the postsynaptic terminal of excitatory synapses. We found that postsynaptic proteins are hierarchically assembled into signaling complexes and supercomplexes, and these are distributed between synapses to generate synapse types. Whole-brain synapse maps revealed striking synaptic diversity and a “synaptome architecture” of the brain. Synaptome maps correlate with the structural and functional connectome, indicating that maps of synapse molecular diversity are features of systems-level organization.
We also analyzed the postsynaptic responses to elementary patterns of neural activity and a repertoire of innate and learned behaviors in mice with mutations in >50 postsynaptic proteins. The results of these experiments, together with the synaptome map data indicate that synapse diversity is a means of storing and recalling information in the brain. Synapse proteome complexity may generate a virtually limitless number of synapse types and synaptome maps offering immense information storage that can be accessed by patterns of activity. Autism and schizophrenia mutations disrupted the hierarchical assembly of supercomplexes and synaptome map architecture, the responses to sequences of activity and the behavioral repertoire.
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