Neurotransmitter classification from electron microscopy images at synaptic sites in Drosophila melanogaster.


Journal

Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066

Informations de publication

Date de publication:
09 May 2024
Historique:
received: 02 04 2023
revised: 04 10 2023
accepted: 13 03 2024
medline: 11 5 2024
pubmed: 11 5 2024
entrez: 10 5 2024
Statut: ppublish

Résumé

High-resolution electron microscopy of nervous systems has enabled the reconstruction of synaptic connectomes. However, we do not know the synaptic sign for each connection (i.e., whether a connection is excitatory or inhibitory), which is implied by the released transmitter. We demonstrate that artificial neural networks can predict transmitter types for presynapses from electron micrographs: a network trained to predict six transmitters (acetylcholine, glutamate, GABA, serotonin, dopamine, octopamine) achieves an accuracy of 87% for individual synapses, 94% for neurons, and 91% for known cell types across a D. melanogaster whole brain. We visualize the ultrastructural features used for prediction, discovering subtle but significant differences between transmitter phenotypes. We also analyze transmitter distributions across the brain and find that neurons that develop together largely express only one fast-acting transmitter (acetylcholine, glutamate, or GABA). We hope that our publicly available predictions act as an accelerant for neuroscientific hypothesis generation for the fly.

Identifiants

pubmed: 38729112
pii: S0092-8674(24)00307-6
doi: 10.1016/j.cell.2024.03.016
pii:
doi:

Substances chimiques

Neurotransmitter Agents 0
gamma-Aminobutyric Acid 56-12-2

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

2574-2594.e23

Informations de copyright

Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Nils Eckstein (N)

HHMI Janelia Research Campus, Ashburn, VA, USA; Institute of Neuroinformatics UZH/ETHZ, Zurich, Switzerland.

Alexander Shakeel Bates (AS)

Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, UK; Centre for Neural Circuits and Behaviour, The University of Oxford, Tinsley Building, Mansfield Road, Oxford OX1 3SR, UK; Department of Neurobiology and Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, USA.

Andrew Champion (A)

Drosophila Connectomics Group, Department of Zoology, University of Cambridge, Cambridge, UK.

Michelle Du (M)

HHMI Janelia Research Campus, Ashburn, VA, USA.

Yijie Yin (Y)

Drosophila Connectomics Group, Department of Zoology, University of Cambridge, Cambridge, UK.

Philipp Schlegel (P)

Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, UK; Drosophila Connectomics Group, Department of Zoology, University of Cambridge, Cambridge, UK.

Alicia Kun-Yang Lu (AK)

HHMI Janelia Research Campus, Ashburn, VA, USA.

Thomson Rymer (T)

HHMI Janelia Research Campus, Ashburn, VA, USA.

Samantha Finley-May (S)

HHMI Janelia Research Campus, Ashburn, VA, USA.

Tyler Paterson (T)

HHMI Janelia Research Campus, Ashburn, VA, USA.

Ruchi Parekh (R)

HHMI Janelia Research Campus, Ashburn, VA, USA.

Sven Dorkenwald (S)

Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA.

Arie Matsliah (A)

Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA.

Szi-Chieh Yu (SC)

Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA.

Claire McKellar (C)

Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA.

Amy Sterling (A)

Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA.

Katharina Eichler (K)

Drosophila Connectomics Group, Department of Zoology, University of Cambridge, Cambridge, UK.

Marta Costa (M)

Drosophila Connectomics Group, Department of Zoology, University of Cambridge, Cambridge, UK.

Sebastian Seung (S)

Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA.

Mala Murthy (M)

Princeton Neuroscience Institute, Princeton University, Princeton, NJ, USA.

Volker Hartenstein (V)

Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, USA.

Gregory S X E Jefferis (GSXE)

Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, UK; Drosophila Connectomics Group, Department of Zoology, University of Cambridge, Cambridge, UK. Electronic address: jefferis@mrc-lmb.cam.ac.uk.

Jan Funke (J)

HHMI Janelia Research Campus, Ashburn, VA, USA. Electronic address: funkej@janelia.hhmi.org.

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