Sequencing the Connectome
Connectivity determines the function of neural circuits. Historically, circuit mapping has usually been viewed as a problem of microscopy, but no current method can achieve high-throughput mapping of entire circuits with single neuron precision. Here we describe a novel approach to determining connectivity. We propose BOINC (“barcoding of individual neuronal connections”), a method for converting the problem of connectivity into a form that can be read out by high-throughput DNA sequencing. The appeal of using sequencing is that its scale—sequencing billions of nucleotides per day is now routine—is a natural match to the complexity of neural circuits. An inexpensive high-throughput technique for establishing circuit connectivity at single neuron resolution could transform neuroscience research.
Neuroscientists seek neural explanations of perception, thought, and behavior. What does such an explanation look like? One of the earliest examples is Descartes' account [1] of the reflex withdrawal of a foot from a fire (Figure 1A ). Descartes hypothesized that small particles of the fire displace the skin of the foot, which pulls on a tiny thread and thereby opens a pore in the pineal gland, releasing animal spirits, which flow back via a hollow tube into the foot to cause retraction. Although more modern accounts of the spinal reflex arc differ in important mechanistic and anatomical details, the kernel of Descartes' explanation is both correct and intellectually satisfying: the neural circuit he describes immediately implies the causal relationship between the stimulus and the resultant action. Circuit-level explanations of computation and behavior represent the gold standard.
