Sequencing the Connectome

Understanding how the billions of neurons of the brain are connected – the brain's wiring diagram – would transform neuroscience research. It would bring to light not only possible malformation of these connections that can, early in life, lead to mental retardation, autism or schizophrenia but also the loss of the connections which, later in life, is associated with neurodegenerative diseases such as Alzheimer's. Microscopy presents considerable challenges in such brain research. This Allen Distinguished Investigator and his team is developing a novel approach based on high-throughput DNA sequencing technology. This sequencing technology is the same as that used to sequence the genome, but it has not previously been applied in the context to neural connectivity. Sequencing is already fast – sequencing billions of individual pieces of DNA in a single day is now routine – and, like microprocessor technology, getting faster and cheaper exponentially. Thus by converting brain connectivity from a problem of microscopy to a problem of sequencing, it is rendered tractable using current techniques. The research project has succeeded in generating all the molecular components needed for a proof-of-concept for this revolutionary endeavor.

Affiliated Investigators

Tony Zador, Ph.D.

Cold Spring Harbor Laboratory

Dr. Anthony Zador is the Alle Davis Harris Professor of Biology and Program Chair in Neuroscience at Cold Spring Harbor Laboratory. Dr. Zador uses a combination of computational, electrophysiological and imaging techniques at the molecular, synaptic, cellular, circuit and behavioral levels to study how neural circuits underlie decision making, particularly in the auditory cortex. He has been on the faculty at Cold Spring Harbor Laboratory since 1999. As a M.D.-Ph.D. student at Yale, he trained in theoretical neuroscience and neural networks; this training led him to think about all problems from a mathematical and computational perspective. During this time Dr. Zador collaborated with Christof Koch, who was then at Caltech. He then completed postdoctoral work on synaptic physiology with Chuck Stevens at the Salk Institute. As a postdoc he also organized a series of workshops on Neural Information and Coding. He then broadened the scope of these and co-founded the annual Computational and Systems Neuroscience (COSYNE) meeting, which now draws over 600 participants, and is arguably the leading meeting on theoretical and systems neuroscience.