Towards a Drosophila connectome

Chklovskii et al recently published a paper in Current Opinion in Neurobiology that discusses the problem of attempting to build a map of neural connections (a “connectome”) in the fruit fly. Here is a sweet image of their broad plan for attacking the problem:

Reconstruction pipeline at HHMI's Janelia Farm; red circle in top image is a synapse; doi:10.1016/j.conb.2010.08.002

Here’s how I understand how they reconstruct the sections: First the images are mapped globally using a software program like TrakEM2. Then, individual images are overlapped pairwise by different software on the basis of, e.g., image correlation. These overlapping images are transformed or “connected” together. Finally, transformed images are fit into a global coordinate system using the least squares method of linear regression.

This process is almost exactly how one might solve a jigsaw puzzle, if the puzzle was in 3d, there was no guarantee that you had all of the necessary images, and the results would be one of the most important breakthroughs in neuroscience in some time.

Once the images are built into a 3d image, they need to be segmented into biologically interesting portions, such as the axons and the synapses. This involves the choice of various algorithms for boundary detection, which are improving as the world pours more and more research into image recognition in general. Many of these approaches use the Rand index, which measures similarity between adjacent pixels.

Although it is less sexy, researchers still proofread and annotate these connections manually, and there is software designed specifically for that. Perhaps they could jump on the bandwagon of crowdsourcing and formulate this problem as a public and interactive computer game.

The researchers are currently in the processing of reconstructing 250 columns in the medulla neuropile optic lobe that fills a volume of 90 μm × 90 μm × 80 μm. One column of 250 has so far been reconstructed, and they note that it took two “person years” to do so. So let’s hope that we can get some Moore’s law-like advancement going in the area of neural circuit reconstruction!

Reference

Chklovskii DB, Vitaladevuni S, Scheffer LK. 2010 Semi-automated reconstruction of neural circuits using electron microscopy. Curr Opin Neurobiol. doi:10.1016/j.conb.2010.08.002