Abstract

Sustained changes in mood or action require persistent changes in neural activity, but it has been difficult to identify the neural circuit mechanisms that underlie persistent activity and contribute to long-lasting changes in behavior. Here, we show that a subset of Doublesex+ pC1 neurons in the Drosophila female brain, called pC1d/e, can drive minutes-long changes in female behavior in the presence of males. Using automated reconstruction of a volume electron microscopic (EM) image of the female brain, we map all inputs and outputs to both pC1d and pC1e. This reveals strong recurrent connectivity between, in particular, pC1d/e neurons and a specific subset of Fruitless+ neurons called aIPg. We additionally find that pC1d/e activation drives long-lasting persistent neural activity in brain areas and cells overlapping with the pC1d/e neural network, including both Doublesex+ and Fruitless+ neurons. Our work thus links minutes-long persistent changes in behavior with persistent neural activity and recurrent circuit architecture in the female brain.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. David S Deutsch

    Princeton Neuroscience Institute, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8587-2435
  2. Diego A Pacheco

    Princeton Neuroscience Institute, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Lucas Encarnacion-Rivera

    Princeton Neuroscience Institute, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Talmo D Pereira

    Princeton Neuroscience Institute, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9075-8365
  5. Ramie Fathy

    Princeton Neuroscience Institute, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Jan Clemens

    European Neuroscience Institute, Göttingen, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4200-8097
  7. Cyrille Girardin

    Neuroscience, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Adam J Calhoun

    Princeton Neuroscience Institute, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Elise C Ireland

    Princeton Neuroscience Institute, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Austin T Burke

    Princeton Neuroscience Institute, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Sven Dorkenwald

    Princeton Neuroscience Institute and Department of Computer Science, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Claire E McKellar

    Princeton Neuroscience Institute, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3580-7336
  13. Thomas Macrina

    Princeton Neuroscience Institute and Department of Computer Science, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Ran Lu

    Princeton Neuroscience Institute, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. Kisuk Lee

    Princeton Neuroscience Institute, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  16. Nico Kemnitz

    Princeton Neuroscience Institute, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  17. Dodham Ih

    Princeton Neuroscience Institute, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  18. Manuel Castro

    Princeton Neuroscience Institute, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  19. Akhilesh Halageri

    Princeton Neuroscience Institute, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  20. Chris Jordan

    Princeton Neuroscience Institute, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  21. William Silversmith

    Princeton Neuroscience Institute, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  22. Jingpeng Wu

    Princeton Neuroscience Institute, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  23. H Sebastian Seung

    Princeton Neuroscience Institute and Department of Computer Science, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  24. Mala Murthy

    Princeton Neuroscience Institute, Princeton University, Princeton, United States
    For correspondence
    mmurthy@princeton.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3063-3389

Funding

National Institutes of Health (RF1 MH117815-01)

  • Mala Murthy

National Institutes of Health (R01 NS104899)

  • Mala Murthy

Howard Hughes Medical Institute (Faculty Scholar)

  • Mala Murthy

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

Copyright

© 2020, Deutsch 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

  • 6,523
    views
  • 648
    downloads
  • 78
    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. David S Deutsch
  2. Diego A Pacheco
  3. Lucas Encarnacion-Rivera
  4. Talmo D Pereira
  5. Ramie Fathy
  6. Jan Clemens
  7. Cyrille Girardin
  8. Adam J Calhoun
  9. Elise C Ireland
  10. Austin T Burke
  11. Sven Dorkenwald
  12. Claire E McKellar
  13. Thomas Macrina
  14. Ran Lu
  15. Kisuk Lee
  16. Nico Kemnitz
  17. Dodham Ih
  18. Manuel Castro
  19. Akhilesh Halageri
  20. Chris Jordan
  21. William Silversmith
  22. Jingpeng Wu
  23. H Sebastian Seung
  24. Mala Murthy
(2020)
The neural basis for a persistent internal state in Drosophila females
eLife 9:e59502.
https://doi.org/10.7554/eLife.59502

Share this article

https://doi.org/10.7554/eLife.59502

Further reading

    1. Neuroscience
    Muad Y Abd El Hay, Gretel B Kamm ... Jan Siemens
    Research Article

    The perception of innocuous temperatures is crucial for thermoregulation. The TRP ion channels TRPV1 and TRPM2 have been implicated in warmth detection, yet their precise roles remain unclear. A key challenge is the low prevalence of warmth-sensitive sensory neurons, comprising fewer than 10% of rodent dorsal root ganglion (DRG) neurons. Using calcium imaging of >20,000 cultured mouse DRG neurons, we uncovered distinct contributions of TRPV1 and TRPM2 to warmth sensitivity. TRPV1’s absence – and to a lesser extent absence of TRPM2 – reduces the number of neurons responding to warmth. Additionally, TRPV1 mediates the rapid, dynamic response to a warmth challenge. Behavioural tracking in a whole-body thermal preference assay revealed that these cellular differences shape nuanced thermal behaviours. Drift diffusion modelling of decision-making in mice exposed to varying temperatures showed that TRPV1 deletion impairs evidence accumulation, reducing the precision of thermal choice, while TRPM2 deletion increases overall preference for warmer environments that wildtype mice avoid. It remains unclear whether TRPM2 in DRG sensory neurons or elsewhere mediates thermal preference. Our findings suggest that different aspects of thermal information, such as stimulation speed and temperature magnitude, are encoded by distinct TRP channel mechanisms.

    1. Neuroscience
    Haowen Liu, Lei Li ... Zhitao Hu
    Research Article

    Munc13 plays a crucial role in short-term synaptic plasticity by regulating synaptic vesicle (SV) exocytosis and neurotransmitter release at the presynaptic terminals. However, the intricate mechanisms governing these processes have remained elusive due to the presence of multiple functional domains within Munc13, each playing distinct roles in neurotransmitter release. Here, we report a coordinated mechanism in the Caenorhabditis elegans Munc13 homolog UNC-13 that controls the functional switch of UNC-13 during synaptic transmission. Mutations disrupting the interactions of C1 and C2B with diacylglycerol (DAG) and phosphatidylinositol 4,5-bisphosphate (PIP2) on the plasma membrane induced the gain-of-function state of UNC-13L, the long UNC-13 isoform, resulting in enhanced SV release. Concurrent mutations in both domains counteracted this enhancement, highlighting the functional interdependence of C1 and C2B. Intriguingly, the individual C1 and C2B domains exhibited significantly stronger facilitation of SV release compared to the presence of both domains, supporting a mutual inhibition of C1 and C2B under basal conditions. Moreover, the N-terminal C2A and X domains exhibited opposite regulation on the functional switch of UNC-13L. Furthermore, we identified the polybasic motif in the C2B domain that facilitates SV release. Finally, we found that disruption of C1 and C2B membrane interaction in UNC-13S, the short isoform, leads to functional switch between gain-of-function and loss-of-function. Collectively, our findings provide a novel mechanism for SV exocytosis wherein UNC-13 undergoes functional switches through the coordination of its major domains, thereby regulating synaptic transmission and short-term synaptic plasticity.