The cellular architecture of memory modules in Drosophila supports stochastic input integration

  1. Omar A Hafez
  2. Benjamin Escribano
  3. Rouven L Ziegler
  4. Jan J Hirtz
  5. Ernst Niebur  Is a corresponding author
  6. Jan Pielage  Is a corresponding author
  1. Johns Hopkins University, United States
  2. University of Kaiserslautern, Germany

Abstract

The ability to associate neutral stimuli with valence information and to store these associations as memories forms the basis for decision making. To determine the underlying computational principles, we build a realistic computational model of a central decision module within the Drosophila mushroom body (MB), the fly's center for learning and memory. Our model combines the electron microscopy-based architecture of one MB output neuron (MBON-α3), the synaptic connectivity of its 948 presynaptic Kenyon cells (KCs), and its membrane properties obtained from patch-clamp recordings. We show that this neuron is electrotonically compact and that synaptic input corresponding to simulated odor input robustly drives its spiking behavior. Therefore, sparse innervation by KCs can efficiently control and modulate MBON activity in response to learning with minimal requirements on the specificity of synaptic localization. This architecture allows efficient storage of large numbers of memories using the flexible stochastic connectivity of the circuit.

Data availability

All data generated or analysed in this study are included in the manuscript.All simulation files and the code and data files needed to replicate the simulations are available as a permanent and freely accessible data collection at the Johns Hopkins University Data Archive:https://doi.org/10.7281/T1/HRK27V.This includes the simulation code itself (python), the structural EM reconstruction of MBON-alpha3 (swc), the EM reconstruction of the related MBON used to model the axon and synaptic terminal structures (swc), the synapse locations as coordinate data (json), and the synapse locations by MBON section (json). Parameter values for model definition and individual simulations are specified within the code files and outlined in each figure legend where appropriate.

Article and author information

Author details

  1. Omar A Hafez

    Zanvyl Krieger Mind/Brain Institute, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Benjamin Escribano

    Department of Biology, University of Kaiserslautern, Kaiserslautern, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Rouven L Ziegler

    Department of Biology, University of Kaiserslautern, Kaiserslautern, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3050-7692
  4. Jan J Hirtz

    Department of Biology, University of Kaiserslautern, Kaiserslautern, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Ernst Niebur

    Zanvyl Krieger Mind/Brain Institute, Johns Hopkins University, Baltimore, United States
    For correspondence
    niebur@jhu.edu
    Competing interests
    The authors declare that no competing interests exist.
  6. Jan Pielage

    Department of Biology, University of Kaiserslautern, Kaiserslautern, Germany
    For correspondence
    pielage@bio.uni-kl.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5115-5884

Funding

National Institutes of Health (R01DC020123)

  • Ernst Niebur

National Institutes of Health (R01DA040990)

  • Ernst Niebur

National Institutes of Health (R01EY027544)

  • Ernst Niebur

National Institutes of Health (Medical Scientist Training Program 708 Training Grant T32GM136651)

  • Ernst Niebur

National Science Foundation (1835202)

  • Ernst Niebur

Bundesministerium für Bildung und Forschung (FKZ 01GQ2105)

  • Jan Pielage

Deutsche Forschungsgemeinschaft (INST 248/293-1)

  • Jan Pielage

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2023, Hafez et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,804
    views
  • 223
    downloads
  • 5
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Omar A Hafez
  2. Benjamin Escribano
  3. Rouven L Ziegler
  4. Jan J Hirtz
  5. Ernst Niebur
  6. Jan Pielage
(2023)
The cellular architecture of memory modules in Drosophila supports stochastic input integration
eLife 12:e77578.
https://doi.org/10.7554/eLife.77578

Share this article

https://doi.org/10.7554/eLife.77578

Further reading

    1. Neuroscience
    Bhanu Priya Somashekar, Upinder Singh Bhalla
    Research Article

    Co-active or temporally ordered neural ensembles are a signature of salient sensory, motor, and cognitive events. Local convergence of such patterned activity as synaptic clusters on dendrites could help single neurons harness the potential of dendritic nonlinearities to decode neural activity patterns. We combined theory and simulations to assess the likelihood of whether projections from neural ensembles could converge onto synaptic clusters even in networks with random connectivity. Using rat hippocampal and cortical network statistics, we show that clustered convergence of axons from three to four different co-active ensembles is likely even in randomly connected networks, leading to representation of arbitrary input combinations in at least 10 target neurons in a 100,000 population. In the presence of larger ensembles, spatiotemporally ordered convergence of three to five axons from temporally ordered ensembles is also likely. These active clusters result in higher neuronal activation in the presence of strong dendritic nonlinearities and low background activity. We mathematically and computationally demonstrate a tight interplay between network connectivity, spatiotemporal scales of subcellular electrical and chemical mechanisms, dendritic nonlinearities, and uncorrelated background activity. We suggest that dendritic clustered and sequence computation is pervasive, but its expression as somatic selectivity requires confluence of physiology, background activity, and connectomics.

    1. Neuroscience
    Geoffrey W Meissner, Allison Vannan ... FlyLight Project Team
    Research Article

    Techniques that enable precise manipulations of subsets of neurons in the fly central nervous system (CNS) have greatly facilitated our understanding of the neural basis of behavior. Split-GAL4 driver lines allow specific targeting of cell types in Drosophila melanogaster and other species. We describe here a collection of 3060 lines targeting a range of cell types in the adult Drosophila CNS and 1373 lines characterized in third-instar larvae. These tools enable functional, transcriptomic, and proteomic studies based on precise anatomical targeting. NeuronBridge and other search tools relate light microscopy images of these split-GAL4 lines to connectomes reconstructed from electron microscopy images. The collections are the result of screening over 77,000 split hemidriver combinations. Previously published and new lines are included, all validated for driver expression and curated for optimal cell-type specificity across diverse cell types. In addition to images and fly stocks for these well-characterized lines, we make available 300,000 new 3D images of other split-GAL4 lines.