Horizons in Molecular Biology 2017: C. Elegans: The Hydrogen Atom of Systems Neuroscience?

What would a satisfyingly complete understanding of how behavior arises from of the internal processing of an organism’s nervous system look like? The closest example we have is how the internal molecular life of E. coli drives the effective but frenetic dance of chemotaxis, a story elucidated over many decades as a beautiful combination of experiment and theory. There is a growing consensus that we must “look under the hood” in great detail and at high density to make real strides-- to that end, we recently achieved brain-wide cellular-resolution neuronal imaging in the worm using volumetric microscopy and genetic engineering. It turns out that the worm has a very rich internal mental life in the form of highly structured intrinsic brain dynamics. We have been able to decode the behavioral intent of the animal at all times during these trials, effectively reading the mind of the worm. Our work is now focused on two key areas: (1) how are these organized brain dynamics set up by the anatomical structure and signaling properties of neurons and their connections? And (2) how do these brain dynamics produce the computations that underlie appropriate behavior, such as action selection? For these questions we are developing technologies – using software, hardware, and genomic engineering- to interrogate and perturb cellular properties and network dynamics during a live recording… and formulate and test theories of how a nervous system computes behavior via structured network dynamics.

Reference: Kato S, Kaplan HS, Schrödel T, Skora S, Lindsay TH, Yemini E, Lockery S, Zimmer M. Global brain dynamics embed the motor command sequence of Caenorhabditis elegans. Cell. 2015 Oct 22; 163(3):656-69. PMID: 26478179.

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