Relating structure and function in synapse-level wiring diagrams

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PI: Litwin-Kumar, Ashok  


Institution: Columbia University

Title: Relating structure and function in synapse-level wiring diagrams  

Grant #: EB029858

Status: Active


Modern electron-microscopy (EM) imaging and analysis methods now permit the comprehensive reconstruction of all neurons and synapses in large volumes of brain tissue or the entire brains of individual organisms. However, relating this structure to function is difficult. The rapidly increasing scale of these datasets requires the development of new quantitative techniques to address this challenge. We take a combined data analysis and modeling approach that is informed by large-scale EM datasets collected by our experimental collaborators.

Our methods extend state of the art by incorporating multiple sources of information about neuronal connectivity and function to explain structure in EM wiring diagrams. They also leverage recent advances in recurrent neural network optimization to use this structure to constrain models of neural dynamics. The methods will be of interest for researchers working across many model organisms for which EM reconstruction efforts have been completed or are currently underway. We expect that the methods will provide a template for integrating structural information into modeling efforts across these varied systems.

A github repository containing tools for loading, visualizing, and analyzing connectome data from the recent Janelia hemibrain (Scheffer et al. 2020), larval connectome (Winding et al. 2023), and FlyWire (Dorkenwald et al. 2022) datasets can be found at:

Project overview slide:


Associated publications:

S. Muscinelli, M. Wagner & A. Litwin-Kumar (2023). Optimal routing to cerebellum-like structures. Nature Neuroscience, in press.

D. Yamada, D. Bushey, F. Li, K. L. Hibbard, M. Sammons, J. Funke, A. Litwin-Kumar, T. Hige & Y. Aso (2023). Hierarchical architecture of dopaminergic circuits enables second-order conditioning in Drosophila. eLife 12: e79042.

T. T. Hayashi, A. J. MacKenzie, I. Ganguly, K. E. Ellis, H. M. Smihula, M. S. Jacob, A. Litwin-Kumar & S. J. C. Caron (2022). Mushroom body input connections form independently of sensory activity in Drosophila melanogaster. Current Biology 32(18): 4000–4012.

L. Jiang & A. Litwin-Kumar (2021). Models of heterogeneous dopamine signaling in an insect learning and memory center. PLOS Computational Biology 17(8): e1009205.

B. Mark, S. Lai, A. A. Zarin, L. Manning, H. Q. Pollington, A. Litwin-Kumar, A. Cardona, J. W. Truman & C. Q. Doe (2021). A developmental framework linking neurogenesis and circuit formation in the Drosophila CNS. eLife 10: e67510.

F. Li, J. W. Lindsey, E. C. Marin, N. Otto, M. Dreher, G. Dempsey, I. Stark, A. S. Bates, M. W. Pleijzier, P. Schlegel, A. Nern, S. Takemura, N. Eckstein, T. Yang, A. Francis, A. Braun, R. Parekh, M. Costa, L. K. Scheffer, Y. Aso, G. S. X. E. Jefferis, L. F. Abbott, A. Litwin-Kumar, S. Waddell & G. M. Rubin (2020). The connectome of the adult Drosophila mushroom body provides insights into function. eLife 9: e62576.

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