Completed Brain & Nervous System Genetics & Molecular Biology

The Human Brain Synaptome Project

In plain English

AI plain-English summary

The first atlas of the human brain’s synapses will map the location, molecular makeup, and physical structure of trillions of individual connections across the whole organ. Synapses are the junctions where neurons communicate, and their disruption underlies countless brain disorders—from Alzheimer’s to schizophrenia to traumatic injury. Until now, no one has mapped the human brain’s full complement of synapse subtypes at scale. This project fills that gap by creating the Human Synaptome Atlas, initially profiling all major brain regions in three individuals and the prefrontal cortex in 100 people aged 20 to 80. The team has already built a breakthrough pipeline for mapping billions of synapses in the mouse brain; here they scale that technology—called SYNSTAR—to handle the human brain’s vastly greater size and complexity. If successful, the atlas will become a fundamental reference for understanding how synapse diversity shapes normal brain function and how it goes wrong in disease. This is primarily fundamental science—curiosity-driven work to describe the brain’s basic wiring. But it lays essential groundwork: future studies of genetic disorders, neurodegeneration, and brain injury will use the atlas to pinpoint exactly which synapse types are lost or altered, potentially guiding new diagnostic tools or therapies.

View original technical description
We will create the first atlas of the human brain showing the location, molecular composition and physical features of trillions of single synapses at the whole-brain scale. The Human Synaptome Atlas will reveal the distribution of excitatory and inhibitory synapse subtypes in all major areas of the brain in three normal individuals and in the prefrontal cortex of 100 normal individuals (20-80 years of age). Toward this, we have reported a breakthrough technology pipeline enabling mapping of billions of individual synapses to generate the mouse brain synaptome (PMC6117470). To address the challenges and opportunities presented by the human brain, we will: 1. Establish the next-generation synaptome mapping pipeline – SYNSTAR – scalable to the size and complexity of the human synaptome. 2. Generate novel reference resources and tools for analysis and interactive visualisation of human synaptomes. 3. Integrate the atlas with international strategic programmes mapping human brain anatomy and function from the molecular and cellular scale to whole-brain networks. The Human Synaptome Atlas and SYNSTAR will provide a foundation for the study of the normal and diseased brain including the many genetic disorders, neurodegenerative conditions and brain injuries that damage synapses. Keywords: Human, Brain, Synapse, Synaptome, Postsynaptic, Proteome, Atlas

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Researchers

Colin Smith (EPMC Awardee)Michael Hawrylycz (EPMC Awardee)Seth Grant (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Molecular synapse imaging technology and resources
Defining the Human Synapse Proteome
Synaptome architecture of the single neuron
The synaptome architecture of the mammalian brain
Molecular organization and dynamics of synapse diversity: novel genetic, imaging and computational approaches

Original classification

Technology Development Grant

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