Sequencing the Connectome

A team of neuroscientists led by Professor Anthony Zador, Ph.D., of Cold Spring Harbor Laboratory have proposed a revolutionary new way to create a connectivity map (“connectome”) of the whole brain of the mouse at the resolution of single neurons: high-throughput DNA sequencing.
The only current method for obtaining the connectome with high precision relies on laboriously examining individual cell-to-cell contacts (synapses) in electron microscopes, which is slow, expensive and labor-intensive. (See A circuit diagram of the mouse brain.)
This reconstruction of serial electron micrographs has yielded what to date is the only complete connectome, that of C. elegans (a nemotode or roundworm). However, even for this simple nervous system, the reconstruction required a heroic effort — more than 50 person-years of labor to collect and analyze the images.
The appeal of using sequencing is that its scale and speed — sequencing billions of nucleotides per day is now routine — is a natural match to the complexity of neural circuits. And it’s getting faster exponentially.
An inexpensive high-throughput technique for establishing circuit connectivity at single neuron resolution could transform neuroscience research, the open-access PLoS Biology paper says.