A Complete Electron Microscopy Volume of the Brain of Adult Drosophila melanogaster

Zhihao Zheng,Davi D Bock,Steven A Calle-Schuler,Corey B Fisher,Iqbal J Ali,Bill Karsh,Matthew Nichols,J Scott Lauritzen,Michael Kazhdan,Nadiya Sharifi,Eric Perlman,Camenzind G Robinson,Omar Torrens,Lucia Kmecova,John A Bogovic,Stephan Saalfeld,Philipp Hanslovsky,Khaled Khairy,Eric T Trautman,Richard D Fetter,Gregory Jefferis ,J W Price ,Daniel E Milkie

doi:10.1016/j.cell.2018.06.019

Abstract

SummaryDrosophila melanogaster has a rich repertoire of innate and learned behaviors. Its 100,000-neuron brain is a large but tractable target for comprehensive neural circuit mapping. Only electron microscopy (EM) enables complete, unbiased mapping of synaptic connectivity; however, the fly brain is too large for conventional EM. We developed a custom high-throughput EM platform and imaged the entire brain of an adult female fly at synaptic resolution. To validate the dataset, we traced brain-spanning circuitry involving the mushroom body (MB), which has been extensively studied for its role in learning. All inputs to Kenyon cells (KCs), the intrinsic neurons of the MB, were mapped, revealing a previously unknown cell type, postsynaptic partners of KC dendrites, and unexpected clustering of olfactory projection neurons. These reconstructions show that this freely available EM volume supports mapping of brain-spanning circuits, which will significantly accelerate Drosophila neuroscience.Video

Highlights

How brain circuits allow animals to implement complex behavior remains a central mystery of neurobiology
We built new hardware and software for high-speed acquisition and processing of serial section transmission electron microscopy (EM) (TEM) images and used this infrastructure to image a whole-fly brain at synaptic resolution (Figure 1)
Retrograde tracing from Kenyon cells (KCs) dendrites provided a complete enumeration of olfactory PN input to the mushroom body (MB) and yielded an improved map of local circuitry in the calyx, the initial site for sampling and processing of sensory information in the MB. This revealed principles of coordinated organization that were invisible in previous work using light level data assembled from many different brains; for example we found a high degree of clustering of PN inputs, which may generate biases in PN-to-KC connectivity and shape how olfactory PN input to the MB is sampled

Summary

Introduction

How brain circuits allow animals to implement complex behavior remains a central mystery of neurobiology. At $8 3 107 mm and $100,000 neurons (Simpson, 2009), the brain of an adult fly is two orders of magnitude larger than that of the fruit fly larva, the next-largest brain imaged at synaptic resolution (Ohyama et al, 2015). This combination of scale and resolution has heretofore been unattainable by volume electron microscopy (EM), the only method capable of simultaneously resolving all neuronal branches and synapses in a given volume of brain tissue (Helmstaedter et al, 2008). We built new hardware and software for high-speed acquisition and processing of serial section transmission EM (TEM) images and used this infrastructure to image a whole-fly brain at synaptic resolution (Figure 1)

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Conclusion