Ome sweet ome: what can the genome tell us about the connectome?

Abstract

Some neuroscientists argue that detailed maps of synaptic connectivity--wiring diagrams--will be needed if we are to understand how the brain underlies behavior and how brain malfunctions underlie behavioral disorders. Such large-scale circuit reconstruction, which has been called connectomics, may soon be possible, owing to numerous advances in technologies for image acquisition and processing. Yet, the community is divided on the feasibility and value of the enterprise. Remarkably similar objections were voiced when the Human Genome Project, now widely viewed as a success, was first proposed. We revisit that controversy to ask if it holds any lessons for proposals to map the connectome.

Figure 1

Scaffolds on which a connectome can be built. (a) A schematic wiring diagram. The best known are Cajal's. An example is his diagram showing the flow of information from peripheral sensory receptors to the spinal cord and brain, then back to motoneurons and muscles. He used arrows to `indicate the direction of descending motor impulses and ascending sensory impressions'. This wiring diagram was pieced together from observations on multiple samples and the direction of current flow was inferred from the structure [35]. (b) A projectome. A well-known example is Van Essen and Felleman's summary of connections among cortical areas associated with vision and some other modalities. Their diagram was compiled from results of tracing and physiological studies by several groups [25].

Figure 2

A connectome. Wiring diagram for the tail of C. Elegans, reconstructed from serial electron micrographs. The width of individual lines is proportional to the relative frequency of synaptic contacts. Lines that end in arrowheads show chemical synapses; lines that end in bars show electrical synapses. Connections to other parts of the nervous system are not included in this diagram, but were reconstructed [36, 3••].