A line attractor encoding a persistent internal state requires neuropeptide signaling
Creators
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1.
California Institute of Technology
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2.
Stanford University
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3.
Howard Hughes Medical Institute
Abstract
Internal states drive survival behaviors, but their neural implementation is poorly understood. Recently, we identified a line attractor in the ventromedial hypothalamus (VMH) that represents a state of aggressiveness. Line attractors can be implemented by recurrent connectivity or neuromodulatory signaling, but evidence for the latter is scant. Here, we demonstrate that neuropeptidergic signaling is necessary for line attractor dynamics in this system by using cell-type-specific CRISPR-Cas9-based gene editing combined with single-cell calcium imaging. Co-disruption of receptors for oxytocin and vasopressin in adult VMH Esr1+ neurons that control aggression diminished attack, reduced persistent neural activity, and eliminated line attractor dynamics while only slightly reducing overall neural activity and sex- or behavior-specific tuning. These data identify a requisite role for neuropeptidergic signaling in implementing a behaviorally relevant line attractor in mammals. Our approach should facilitate mechanistic studies in neuroscience that bridge different levels of biological function and abstraction.
Copyright and License
© 2024 The Author(s). Published by Elsevier Inc.
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Acknowledgement
We thank H. Inagaki, A. Kennedy, B. Weissbourd, and M. Schnitzer for comments on this manuscript; C. Chiu for laboratory management; G. Mancuso and L. Chavarria for administrative assistance; and members of the Anderson lab for helpful comments on this project. We also thank Y. Li, L. Geng, and H. Wang for sharing their OXT-GRAB sensor in advance of publication. G.M. has been supported by post-doctoral fellowships from the Tianqio and Chrissy Chen Institute for Neuroscience, the Helen Hay Whitney Foundation, and the Della Martin Foundation. A.N. is supported by a National Science Scholarship from the Agency of Science, Technology, and Research, Singapore. This work was supported in part by NIH grants NS123916, MH1223612, and MH070053. D.J.A. is an Investigator of the Howard Hughes Medical Institute. The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We support inclusive, diverse, and equitable conduct of research. We acknowledge that this research was conducted at Caltech, which is located on the unceded land of the Indigenous Tongva people.
Funding
G.M. has been supported by post-doctoral fellowships from the Tianqio and Chrissy Chen Institute for Neuroscience, the Helen Hay Whitney Foundation, and the Della Martin Foundation. A.N. is supported by a National Science Scholarship from the Agency of Science, Technology, and Research, Singapore. This work was supported in part by NIH grants NS123916, MH1223612, and MH070053. D.J.A. is an Investigator of the Howard Hughes Medical Institute. The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Contributions
G.M. and D.J.A. conceived the project. G.M. and D.J.A. wrote and prepared the manuscript with input from A.N. G.M. performed all the experiments, with help from B.Y. for microendoscope imaging or from D.-W.K. and S.K. for two-photon slice imaging experiments. A.V. participated in the revision phase of the manuscript. G.M. and A.N. performed quantitative measurements of behavior and microendoscope imaging data. A.N., under the supervision of S.W.L., performed the dynamical system modeling and decoder analyses.
Data Availability
- The source data used in this paper will be deposited in DANDI: #001131 and can be shared by the lead contact upon reasonable request.
- Code used for analyses in this paper is publicly available in the following repositories: https://github.com/lindermanlab/ssm and https://github.com/DJALab/VMHvl_MPOA_dynamics.
- Any additional information required to reanalyze the data reported in the paper is available from the lead contact upon reasonable request.
Code Availability
Code used for analyses in this paper is publicly available in the following repositories: https://github.com/lindermanlab/ssm and https://github.com/DJALab/VMHvl_MPOA_dynamics.
Conflict of Interest
The authors declare no competing interests.
Files
PIIS0092867424009061.pdf
Additional details
Identifiers
- PMCID
- PMC11490375
- PMID
- 39191257
Funding
- Howard Hughes Medical Institute
- Helen Hay Whitney Foundation
- National Institutes of Health
- NS123916
- National Institutes of Health
- MH1223612
- National Institutes of Health
- MH070053
Dates
- Available
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2024-08-26Published online
Caltech Custom Metadata
- Caltech groups
- Division of Biology and Biological Engineering (BBE) , Tianqiao and Chrissy Chen Institute for Neuroscience
- Publication Status
- Published