A systems analysis of neural connectivity and functionality in Caenorhabditis elegans

Part I considers the stereotypic patterns of synaptic connectivity in neural circuits, referred to as wiring specificity. Two aspects of wiring specificity are lamina specificity - placing synaptic partners in close spatial proximity - and synaptic specificity - making the appropriate synaptic connections among many physically adjacent neurons. Combinatorial expression patterns of surface proteins could be used to uniquely label neurons for the purposes of synaptic specificity. To test this model in the worm, the C. elegans nerve ring was volumetrically reconstructed from serial sectioned legacy electron micrographs, which provides detailed spatial and morphological information of neural processes in the nerve ring. Comparing the spatial data with the synaptic wiring diagram shows that the C. elegans nerve ring exhibits both lamina-like specificity and synaptic specificity. Combinatorial expression patterns of CAM genes in nerve ring neurons were analyzed. If a few key conditions regarding gene expression are satisfied, then the number of known combinatorial CAM expression patterns is sufficient to uniquely label neurons and can account for more than 90% of the observed synaptic specificity. Part II develops a new rotatable microfluidic device for simultaneously imaging calcium activity in bilateral neuron pairs within the same animal. Typically when imaging calcium activity in C. elegans, only the left or right side of the animal is imaged. This is due to the natural orientation of the worm which places neurons on the left and right side in different focal planes. Our new device allows the animal to be rotated, placing cells on the right and left side of the animal in the same focal plane.