Group Leader

Albert Cardona

Experimental and comparative connectomics

Albert Cardona
Group Members
  • Elizabeth Barsotti
  • Jiaqi Chen
  • Marc Corrales
  • Daniel Franco Barranco
  • Peter Hague
  • Ana Jesus Correia Da Silva
  • Shi Yan Lee
  • Ishan Makkar
  • Samia Mohinta
  • Lily Pfaffenzeller
  • Ishika Samanta
  • Scott Wilson
  • Yudi Wu
  • Yijie Yin

Animals integrate multiple sensory inputs with memories to select an appropriate behavioural response. Being modularly organised, the output of local signal processing within a brain module is but one of the inputs into another. Hence, to understand how the brain works, we must first map its complete synaptic wiring diagram, the connectome. Then, together with observations of neural activity and behaviour, computational models can capture the known circuit dynamics to tell us how neural circuits implement behaviour.

Whole CNS connectome visualized with 3D neuron reconstructions in brain and nerve cord, illustrating four synaptic connection types and their comprehensive matrix.
Left: A rendering of all neurons in the larval brain reconstructed from electron microscopy using CATMAID software. Right: Most neurons exhibit both an axon and a dendrite (top). While the majority of synapses in brain circuits connect axons to dendrites, approximately 25% occur between axons, a smaller fraction between dendrites, and very few from dendrites to axons. These rare dendrite-to-axon synapses are most notably found in the input neuropil of the insect’s learning and memory centre—the calyx of the mushroom body. Consequently, the synaptic wiring diagram, or connectome, is visualised as four distinct connectivity matrices (bottom).

We are interested in studying connectomes of complete nervous systems, or at the very least of complete brains. We image them with dense labelling techniques such as volume electron microscopy (eFIB-SEM, GridTape TEM and others), to comprehensibly map their complete connectomes with both computer-assisted and automated techniques. We develop computational methods using computer vision and machine learning techniques, and implement them as open source software to assemble continuous volumes, identify synapses and segment neuronal arbors (Fiji/TrakEM2, CATMAID, CATENA). Through cross-modal registration, we bridge the resolution gap to relate neuronal activity imaged with light-sheet microscopes to EM-mapped connectomes. With these data, we formulate neural circuit models to study brain function in silico, dissecting the contribution to behaviour across the scales, from brain modules to circuit motifs and sub-neuron interactions such as axo-axonic synapses.

While our primary focus is on the larval fruit fly, Drosophila, where genetic techniques, prior knowledge, reduced dimensions and numerically-reduced complexity offer outstanding experimental accessibility and reproducibility, we also study the nervous system of pygmy squids (Idiosepius sp.), simple chordates such as the lancelet (Amphioxus sp.), the flour beetle (Tribolium castaneum), small lizards (Sphaerodactylus sp.) and others. Particular emphasis is given to neural circuits for learning and memory, and for vision and olfaction, in the context of both the wild-type and disease models.

Phylogenetic tree illustrating the evolutionary relationships and diversity of six model organisms with representative images.
The group aims to map, analyse and compare the connectomes, or synaptic wiring diagrams, of suitably small animals sampled across the entire animal phylogenetic tree, including nematodes, arthropods, cephalopods, cephalochordates, and reptiles.

Selected Publications

The connectome of an insect brain.Winding M, Pedigo BD, Barnes CL, Patsolic HG, Park Y, Kazimiers T, Fushiki A, Andrade IV, Khandelwal A, Valdes-Aleman J, Li F, Randel N, Barsotti E, Correia A, Fetter RD, Hartenstein V, Priebe CE, Vogelstein JT, Cardona A, Zlatic MScience 379(6636): eadd9330 (2023)
Comparative Connectomics Reveals How Partner Identity, Location, and Activity Specify Synaptic Connectivity in Drosophila.Valdes-Aleman J, Fetter RD, Sales EC, Heckman EL, Venkatasubramanian L, Doe CQ, Landgraf M, Cardona A, Zlatic MNeuron 109(1): 105-122.e7 (2021)
The complete connectome of a learning and memory centre in an insect brain.Eichler K, Li F, Litwin-Kumar A, Park Y, Andrade I, Schneider-Mizell CM, Saumweber T, Huser A, Eschbach C, Gerber B, Fetter RD, Truman JW, Priebe CE, Abbott LF, Thum AS, Zlatic M, Cardona ANature 548(7666): 175-182 (2017)
Quantitative neuroanatomy for connectomics in Drosophila.Schneider-Mizell CM, Gerhard S, Longair M, Kazimiers T, Li F, Zwart MF, Champion A, Midgley FM, Fetter RD, Saalfeld S, Cardona AElife 5: (2016) Epub