Wiring Economy and Volume Exclusion Determine Neuronal Placement in the Drosophila Brain

Wiring economy has successfully explained the individual placement of neurons in simple nervous systems like that of Caenorhabditis elegans [ [1] , [2] and [3] ] and the locations of coarser structures like cortical areas in complex vertebrate brains [4]. However, it remains unclear whether wiring economy can explain the placement of individual neurons in brains larger than that of C. elegans. Indeed, given the greater number of neuronal interconnections in larger brains, simply minimizing the length of connections results in unrealistic configurations, with multiple neurons occupying the same position in space. Avoiding such configurations, or volume exclusion, repels neurons from each other, thus counteracting wiring economy. Here we test whether wiring economy together with volume exclusion can explain the placement of neurons in a module of the Drosophila melanogaster brain known as lamina cartridge [ [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] and [13] ]. We used newly developed techniques for semiautomated reconstruction from serial electron microscopy (EM) [14] to obtain the shapes of neurons, the location of synapses, and the resultant synaptic connectivity. We show that wiring length minimization and volume exclusion together can explain the structure of the lamina microcircuit. Therefore, even in brains larger than that of C. elegans, at least for some circuits, optimization can play an important role in individual neuron placement.
We are grateful to Richard Fetter for assistance in EM imaging and Janelia FlyEM Project Team and Aljoshcha Nern for helpful comparisons with images from Gal4-driven expression of green fluorescent protein in lamina cells. M.R.-A. acknowledges a Formación del Personal de Investigación (FPI) fellowship from Ministerio de Ciencia e Innovación (MICINN) and support from the Janelia Farm Research Campus (JFRC) (Howard Hughes Medical Institute [HHMI]) visitor program; G.G.d.P. acknowledges funding by MICINN (Spain) as Plan Nacional, including a FPI fellowship, and as partners of the ERASysBio+ initiative supported under the EU ERA-NET Plus scheme in FP7, and support from the JFRC (HHMI) visitor program. I.A.M. also acknowledges support from the JFRC (HHMI) visitor program.