The network and the synapse: 100 years after Cajal

Abstract

A century ago, Ram ón y Cajal proposed that the brain consisted of huge numbers of neurons that communicated with each other through junctions called synapses. Today we routinely monitor single neuron and single synapse responses, and we have elaborate maps of connections between different regions of the brain. What we lack is a way to bridge these two scales of representing neuronal circuits. The challenges in doing so are formidable: even a small mammalian neuronal circuit has many thousands of neurons and millions of synapses. Can we keep track of individual cells and synapses in this crowd? Here we examine how two recent techniques may complement each other to do so. The recent "Brainbow" method is a way to color-code cells and their projections, so we can see which cells come near each other, but cannot be sure they connect. Functional circuit mapping tells us about connections between cells, but we cannot identify more than a handful at a time. Together these methods may fill in each other's blanks and give us brain wiring diagrams that combine scale and precision.