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Department of Physiology, Development and Neuroscience

 

Research

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.

Collaborators

Marta Zlatic (Zoology, Cambridge Univ & HHMI Janelia, USA)
James W. Truman (HHMI Janelia and University of Washington)
Harald Hess (HHMI Janelia)
Philipp Keller (HHMI Janelia)
Carey E. Priebe (Johns Hopkins University, USA)
Ashok Litwin-Kumar (Columbia University, USA)
Larry Abbott (Columbia University, USA)
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 S. Thum (University of Leipzig, Germany)
Bertram Gerber (Leibniz Institute for Neurobiolgy, Magdeburg, Germany)
Chris Q. Doe (University of Oregon at Eugene, USA)
Simon Sprecher (University of Friburg, Switzerland)
Matthieu Louis (UCSB, USA)

Publications

Key publications: 

Barnes CL, Bonnéry D, Cardona A. Synaptic counts approximate synaptic contact area in Drosophila. bioRxiv. 2020 Jan 1.

Valdes-Aleman J, Fetter RD, Sales EC, Doe CQ, Landgraf M, Cardona A, Zlatic M.Comparative connectomics reveals how partner identity, location, and activity specify synaptic connectivity in Drosophila. Neuron 2020, 109 (1), 105-122. e7

Eschbach C, Fushiki A, Winding M, Afonso B, Andrade IV, Cocanougher BT, Eichler K, Gepner R, Si G, Valdes-Aleman J, Gershow M. Circuits for integrating learnt and innate valences in the fly brain. bioRxiv. 2020 Jan 1.

Cocanougher BT, Wittenbach JD, Long X, Kohn AB, Norekian TP, Yan J, Colonell J, Masson JB, Truman JW, Cardona A, Turaga S, Singer RH, Moroz L, Zlatic M. Comparative single-cell transcriptomics of complete insect nervous systems. bioRxiv. 2019 Jan 1:785931.

Eschbach C, Fushiki A, Winding M, Schneider-Mizell CM, Shao M, Arruda R, Eichler K, Valdes-Aleman J, Ohyama T, Thum AS, Gerber B. Recurrent architecture for adaptive regulation of learning in the insect brain. Nature neuroscience. 2020 Apr;23(4):544-55.

Eichler K, Li F, Litwin-Kumar A, Park Y, Andrade I, Schneider-Mizell CM, Saumweber T, Huser A, Eschbach C, Gerber B, Fetter RD. The complete connectome of a learning and memory centre in an insect brain. Nature. 2017 Aug 9;548(7666):175. doi: 10.1038/nature23455

Gerhard S, Andrade I, Fetter RD, Cardona A, Schneider-Mizell CM. Conserved neural circuit structure across Drosophila larval development revealed by comparative connectomics. eLife. 2017 Oct 23;6:e29089.

Jovanic T, Schneider-Mizell C, Shao M, Masson JB, Denisov G, Fetter RD, Mensh BD, Truman JW, 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

Teaching and Supervisions

Teaching: 

Module N3, neuroscience, lectures on "Control of Action".

Professor
MRC Investigator (Programme Leader) at the MRC LMB
Wellcome Trust Investigator
Picture of Dr Albert  Cardona

Contact Details

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