Wellcome Trust Investigator
Group Leader at the Howard Hughes Medical Institute at Janelia, USA
Our lab is interested in understanding how the brain works as a whole. We start from the realization that every area of the brain relays information to many others. Therefore, understanding any one aspect of brain function primarily associated with a particular area requires acquiring some understanding first about many other areas.
This impossible conundrum posed by the pervasive interconnectivity can be approached by first obtaining a map of all neuronal connections, as well as identifying individual neurons capable of eliciting or disrupting specific behaviors. The synaptic wiring diagram of small brains, such as that of the fruit fly larva, can be mapped with relative ease from serial electron microscopy, partly thanks to technology that we and others have developed. The circuits maps that we have obtained so far have proven extraordinarily useful in formulating hypotheses of circuit function and constructing computational models that can reproduce observed behaviors. The neural-behavior maps generated by our collaborators in the Zlatic lab enables us to prioritize specific neurons and areas for reconstruction.
Clear handles into the yarn ball that is the brain are its inputs and outputs, that is, its sensory and motor systems. As a first approximation, everything in between can be thought of as a black box that implements a history-dependent sensorimotor transformation. But in acquiring some structural and functional understanding of the first-order networks for sensation and motor control, the second-order neuronal layer becomes approachable. Therefore we concentrated first in mapping the wiring diagram of the optic, olfactory and somatosensory systems, among others, as well as the motor systems, and are now studying deeper areas of the nervous system such as the mushroom bodies, known to mediate associative memories, and the central complex, known to mediate spatial learning and motor planning.
In the context of known circuitry, and thanks to the genetic tools for the targeted manipulation and monitoring of neural function in Drosophila, we are unveiling the contribution of higher-order neurons to specific functions, one layer and one identified neuron at a time. In acquiring an understanding of some areas of the brain we complete the inputs and outputs of deeper areas, therefore enabling the study of their contributions to specific behaviors. In summary, by mapping the wiring diagram, observing behavior, monitoring and altering neural activity with electrophysiology and optophysiology, and modeling circuit function, we pry open the black box and acquire an understanding of how the nervous system works.
Marta Zlatic (Zoology, Cambridge Univ & HHMI Janelia, USA)
Harald Hess (HHMI Janelia)
Matthias Landgraf (Zoology, Cambridge Univ)
Greg SX Jefferis (MRC-LMB)
Stefan Pulver (University of St Andrews)
Akinao Nose (University of Tokyo, Japan)
Michael Pankratz (LIMES Institute, University of Bonn, Germany)
Andreas Thum (University of Konstanz, Germany)
Bertram Gerber (Leibniz Institute for Neurobiolgy, Magdeburg, Germany)
Chris Q. Doe (University of Oregon at Eugene, USA)
Simon Sprecher (Univesity of Friburg, Switzerland)
Matthieu Louis (UCSB, USA)
Module N3, neuroscience, lectures on "Control of Action".
Jovanic T, Schneider-Mizell CMartin, Shao M, Masson JB, Denisov G, Fetter RDoty, Mensh BDaren, Truman JWilliam, Cardona A, Zlatic M, (2016) Competitive disinhibition mediates behavioral choice and sequences in Drosophila. Cell. 2016 Oct 5;167(3):858-70. doi: 10.1016/j.cell.2016.09.009
Berck ME, Khandelwal A, Claus L, Hernandez-Nunez L, Si G, Tabone CJ, Li F, Truman JW, Fetter RD, Louis M, Samuel ADt, Cardona A, (2016), The wiring diagram of a glomerular olfactory system. eLife. 2016 May 13;5:. doi: 10.7554/eLife.14859
Schneider-Mizell CM, Gerhard S, Longair M, Kazimiers T, Li F, Zwart M, Champion A, Midgley F, Fetter RD, Saalfeld S, Cardona A, (2016), Quantitative neuroanatomy for connectomics in Drosophila eLife. 2016 Mar 18:e12059. doi: 10.7554/eLife.12059
Fushiki A, Zwart MF, Kohsaka H, Fetter RD, Cardona A, Nose A, (2016) A circuit mechanism for the propagation of waves of muscle contraction in Drosophila. eLife. 2016 Feb 18;5:. doi: 10.7554/eLife.13253
Ohyama T, Schneider-Mizell CM, Fetter RD, Aleman JValdes, Franconville R, Rivera-Alba M, Mensh BD, Branson KM, Simpson JH, Truman JW, Cardona A, Zlatic M (2015) A multilevel multimodal circuit enhances action selection in Drosophila. Nature. 2015 Apr 20;520(7549):633-9. doi: 10.1038/nature14297
Saalfeld S, Fetter RD, Cardona A, Tomancak P, (2012), Elastic volume reconstruction from series of ultra-thin microscopy sections. Nature Methods. 2012 Jul;9(7):717-20. doi: 10.1038/nmeth.2072
Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, Preibisch S, Rueden C, Saalfeld S, Schmid B, Tinevez JY, White DJames, Hartenstein V, Eliceiri K, Tomancak P, Cardona A, (2012), Fiji: an open-source platform for biological-image analysis. Nature Methods. 2012 Jul;9(7):676-82. doi: 10.1038/nmeth.2019