Natural events present multiple types of sensory cues, each detected by a specialized sensory modality. Combining information from several modalities is essential for the selection of appropriate actions. Key to understanding multimodal computations is determining the structural patterns of multimodal convergence and how these patterns contribute to behaviour. Modalities could converge early, late or at multiple levels in the sensory processing hierarchy. Here we show that combining mechanosensory and nociceptive cues synergistically enhances the selection of the fastest mode of escape locomotion in Drosophila larvae. In an electron microscopy volume that spans the entire insect nervous system, we reconstructed the multisensory circuit supporting the synergy, spanning multiple levels of the sensory processing hierarchy. The wiring diagram revealed a complex multilevel multimodal convergence architecture. Using behavioural and physiological studies, we identified functionally connected circuit nodes that trigger the fastest locomotor mode, and others that facilitate it, and we provide evidence that multiple levels of multimodal integration contribute to escape mode selection. We propose that the multilevel multimodal convergence architecture may be a general feature of multisensory circuits enabling complex input–output functions and selective tuning to ecologically relevant combinations of cues.
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We thank G. Rubin and the Janelia Fly EM Project for the gift of the comprehensive image dataset of the larval nervous system; S. Lauchie and A. Brothers for assistance with EM imaging; B. Arruda and T. Dang for assistance with behavioural screens; L. Herren, I. Andrade, K. Floria and A. Berthold van der Bourg for assistance with neuronal reconstruction; G. Rubin, H. Dionne and B. Pfeiffer for GAL4 and Split GAL4 lines; A. Nern and G. Rubin for the single cell FLP-out stocks; J.-M. Knapp for Tsh-LexA stock; H.-H. Li and Janelia Fly Light Project Team for images of neuronal lines; K. Hibbard, M. Mercer, T. Laverty and the rest of Janelia Fly Core for stock construction and fly crosses; G. Denisov for the roll and crawl detection LARA software; E. Trautman, R. Svirskas, C. Weaver and D. Olbris for data analysis pipelines; Y. Park, C. Priebe, D. Naiman and J.-B. Masson for advice on statistical analysis; V. Jayaraman for input on calcium imaging; and W. Denk, B. Dickson, S. Druckmann, B. Gerber, K. Svoboda and C. Zuker for helpful comments on the manuscript. We thank Janelia HHMI for funding. A.C. and C.M.S.-M. were also funded by the Institute of Neuroinformatics of the University of Zurich and ETH Zurich, the SNSF grant 31003A_132969, the Universität Zürich Forschungskredit, and the HHMI Visiting Scientist program at Janelia. The EM image data is available via the Open Connectome Project (http://www.openconnectomeproject.org).
Extended data figures
Contours of larvae automatically tracked with the MWT software in the presence of continuous MD IV activation alone in MD IV>dTRPA1 larvae (32oC). The activation onset was at 0 seconds, the video shows the period from 5 seconds to 20 seconds. Automatic detection of rolling using JAABA is shown. In all videos of larval behavior: pink contours indicate JAABA detected larva is rolling at the time; green contours, LARA software detected larva is crawling at that time; blue contours, larvae are neither rolling, nor crawling – they may be pausing or turning. Note some false negatives – blue contours in larvae that are rolling or crawling. Some larvae roll in response to MD IV activation. The majority of larvae are crawling forward.
Contours of larvae in the presence of continuous 1000 Hz, 6.7 m/s2 vibration alone in MD IV>+ larvae (32oC). The activation onset was at 0 sec, this video shows the period from 5 sec to 20 sec. Almost no rolling is observed in response to vibration. Instead most larvae are crawling forward or turning. Most larvae have blue contours indicating JAABA did not detect rolling events (correctly). Note an occasional pink contour in a non-rolling larva indicating a false positive.
Contours of larvae automatically tracked with the MWT software in the presence of continuous vibration (1000 Hz, 6.7 m/s2) and MD IV activation in MD IV>dTRPA1 larvae (32oC). The activation onset was at 0 sec, the video shows the period from 5 sec to 20 sec. A large number of larvae are rolling and the rolling events are correctly detected by JAABA (pink contours).
Contours of larvae automatically tracked with the MWT software in the presence of continuous thermogenetic activation of Basins in R72F11>dTRPA1 larvae (32oC). The activation onset was at 0 sec, the video shows the period from 5 sec to 20 sec. A large number of larvae are rolling and the rolling events are correctly detected by JAABA (pink contours).
Contours of larvae automatically tracked with the MWT software in control attp2>dTRPA1 larvae (32oC). The temperature was raised at 0 sec and this video shows the period from 5 sec to 20 sec. No larvae are rolling and no contours are pink.
Contours of larvae automatically tracked with the MWT software in the presence of continuous thermogenetic activation of Goro in R69F06>dTRPA1 larvae (32oC). The activation onset was at 0 sec, this video shows the period from 5 sec to 20 sec. A large number of larvae are rolling and the rolling events are correctly detected by JAABA (pink contours).
This video illustrates the complete central nervous system of the first instar larva of Drosophila melanogaster, imaged with transmission electron microscopy. The volume consists of 4840 serial sections of 50 nm in thickness, prepared by Rick D. Fetter and imaged at a resolution of 3.8 x 3.8 nanometers/pixel with the semi-automatic EM imaging software Leginon by Rick D. Fetter and two assistants, Shirley Launchie and Andrea Brothers. The resulting 144,953 image tiles of 4096x4096 pixels each were registered by Albert Cardona and Stephan Saalfeld using the elastic serial section registration methods available in the software TrakEM2.
Black lines indicate arbor, cyan marks show input synapses, red marks show presynaptic sites and the ball indicates the cell body. Dorsal is up.
About this article
Nature Neuroscience (2017)