A rise-to-threshold process for a relative-value decision
Abstract
Whereas progress has been made in the identification of neural signals related to rapid, cued decisions, less is known about how brains guide and terminate more ethologically relevant decisions in which an animal's own behaviour governs the options experienced over minutes. Drosophila search for many seconds to minutes for egg-laying sites with high relative value and have neurons, called oviDNs, whose activity fulfills necessity and sufficiency criteria for initiating the egg-deposition motor programme. Here we show that oviDNs express a calcium signal that (1) dips when an egg is internally prepared (ovulated), (2) drifts up and down over seconds to minutes—in a manner influenced by the relative value of substrates—as a fly determines whether to lay an egg and (3) reaches a consistent peak level just before the abdomen bend for egg deposition. This signal is apparent in the cell bodies of oviDNs in the brain and it probably reflects a behaviourally relevant rise-to-threshold process in the ventral nerve cord, where the synaptic terminals of oviDNs are located and where their output can influence behaviour. We provide perturbational evidence that the egg-deposition motor programme is initiated once this process hits a threshold and that subthreshold variation in this process regulates the time spent considering options and, ultimately, the choice taken. Finally, we identify a small recurrent circuit that feeds into oviDNs and show that activity in each of its constituent cell types is required for laying an egg. These results argue that a rise-to-threshold process regulates a relative-value, self-paced decision and provide initial insight into the underlying circuit mechanism for building this process.
Additional Information
© The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. We thank the Rockefeller University Precision Instrumentation Technologies facility for access to fabrication equipment; the Janelia FlyLight team for generating confocal images of oviDN-GAL4 (in Extended Data Fig. 3b), oviDN-SS1 (Fig. 1e,f) and oviDN input neuron split-GAL4s (Extended Data Fig. 11a–r); the Bloomington Drosophila Stock Center (NIH P400D018537) for various fly stocks; A. Siliciano and V. Ruta for GtACR1 effector flies; M. Wolfer for flies expressing GCaMP in eggs; M. Scanziani for pCAG-Kir2.1Mut-T2A-tdTomato and pCAG-Kir2.1-T2A-tdTomato plasmids (Addgene plasmid nos. 60644 and 60598); G. Rubin for plasmid pJFRC81-10XUAS-IVS-Syn21-GFP-p10 (Addgene plasmid no. 36432); A. DiAntonio for vGluT antibody; M. DeSouto for the template fly drawing that was modified and used throughout the manuscript; Z. Wang for help in developing the first iteration of the fly-tracking setup; K. Fonselius and S. Cohen for initial help in developing tools for computer-assisted manual annotation of egg-deposition events in free behaviour; J. Varikooty, J. Hirokawa and I. Ishida for ideas and help in developing the wheel; J. Weisman for sharing his design for delivery of optogenetic stimulation light; and C. Lyu and J. Green for two-photon and electrophysiology discussions. Research reported in this publication was supported by a Brain Initiative grant from the National Institute of Neurological Disorders and Stroke (no. R01NS121904 to G.M.) and a Leon Levy Foundation fellowship and the Kavli Neural Systems Institute grant to V.V. G.M. is a Howard Hughes Medical Institute Investigator. Data availability: All calcium imaging and fly behaviour time-course datasets analysed in the main figures are available on DANDI archive (calcium imaging data, 000247; fly choice tracking data, 000212; fly behavioural sequence tracking data, 000250). Technical documents (for example, CAD files and plasmid maps) and source data for all scatter plots and histograms are available on Figshare (https://doi.org/10.6084/m9.figshare.c.6505732). Code availability: Scripts for data processing and plotting are available on request. Contributions: V.V. and G.M. conceived the initial study and wrote the manuscript. V.V., with input from G.M., designed and performed experiments, analysed data, interpreted results and decided on new experiments. F.W., K.W. and B.J.D. created the oviDN and oviDN input genetic driver lines, shared preliminary data on oviDNs and provided helpful feedback on experiments and the manuscript. A.C. and A.A. created Kir2.1* and Kir2.1*Mut flies. H.A. developed code for computer-assisted manual annotation of egg-deposition events in free behaviour. The authors declare no competing interests.Attached Files
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Additional details
- PMCID
- PMC10356611
- Eprint ID
- 122465
- Resolver ID
- CaltechAUTHORS:20230725-857038000.36
- P400D018537
- NIH
- R01NS121904
- NIH
- Leon Levy Foundation
- Kavli Neural Systems Institute
- Howard Hughes Medical Institute (HHMI)
- Created
-
2023-08-14Created from EPrint's datestamp field
- Updated
-
2023-08-14Created from EPrint's last_modified field