The reconstruction of entire nervous systems jump started with the completion of the work by Sydney Brenner and collaborators in describing the entire nervous system of the nematode Caenorhabditis elegans. This involved reconstructing every neuron in the worm from thousands of 50 nm serial sections. Since then, any further attempts to reconstruct neuronal tissue have used small stacks of serial sections (20-50 sections) and have focused on specific dendrites or axons, i.e., parts of neurons. It was difficult or impossible to determine to what extent the characteristics of a specific set of neurites in such small samples could be generalized to other regions of the brain, or what type of neurons gave rise to such profiles. The main innovation with which these problems can be overcome now is the progress made in digital image handling: in acquisition speed, in storage capacity, and in processing power for their assembly and analysis.
In my lab, we are examining once again very large volumes of neuronal tissue using serial section transmission electron microscopy. We focus on an organism, the fruit fly Drosophila melanogaster, that provides us with an enormous genetic toolkit for the targeted manipulation and labeling of its cells and tissues.
In the larva of the fruit fly we have the opportunity to reconstruct at least complete functional units of the nervous system, and learn important general principles about wiring patterns and the function of individual components. With the extraordinary toolkit provided by the GAL4/UAS system and the numerous GAL4 driver lines generated over decades by the fly research community, we have now the ability to specifically label single neurons whose identity is unique, and which are morphologically and genetically identifiable from animal to animal. The unique identity of neuron enables us to perform reproducible functional and behavioral assays in the context of known circuitry, in collaboration with the Zlatic lab at HHMI's Janelia Farm Research Campus.
Our model system of choice is the first order sensory processing centers in the abdominal segments of the larval ventral nerve cord, particularly well characterized at the optical microscopy level. Each abdominal hemisegment receives a total of 44 sensory axons, of stereotyped projection. By reconstructing the arborization and synapses of the sensory axons and their interneuron targets, and performing functional assays, we aim at elucidating important principles about the function and capabilities of neural circuits.
As of April 10, 2012