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Published April 21, 2022 | Submitted
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An approximate line attractor in the hypothalamus that encodes an aggressive internal state


The hypothalamus plays a key role in regulating innate behaviors. It is widely believed to function as a system of 'labeled lines', containing behavior-specific neurons with characteristic transcriptomic and connectomic profiles. This view however fails to explain why, although activation of estrogen receptor-1 (Esr1) expressing neurons in the ventromedial hypothalamus (VMHvl) promotes aggression, few VMHvl neurons are tuned to attack. To address this paradox, we adopted an unsupervised dynamical systems framework to analyze population activity among VMHvlEsr1 neurons during aggression. We discovered that this activity contains an "integration" dimension exhibiting slow-ramping dynamics and persistent activity that correlates with escalating aggressiveness. These dynamics are implemented as an approximate line attractor in state space. Our analysis suggests a function for VMHvl to encode the intensity of behavior-relevant motive states using line attractors. This view reconciles observational and perturbational studies of VMHvl, and reveals a new mode of neural computation in the hypothalamus.

Additional Information

The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This version posted April 19, 2022. We thank S. Ganguli and M. Schnitzer for discussions on conceptualizing this project at its inception. We thank H. Inagaki and L.F. Abbott for critical feedback on this manuscript, C. Chiu for laboratory management and G. Mancuso for administrative assistance, and members of the Anderson and Kennedy labs for helpful comments on this project. A. N. is supported by a National Science Scholarship from the Agency of Science, Technology and Research, Singapore. D.J.A. is an Investigator of the Howard Hughes Medical Institute. A.K. is supported by NIH R00MH117264. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Author contributions: D.J.A, A.K and A.N conceived of the project and wrote the manuscript, with input from T.K, B.Y and S.L. A.K performed the clustering analysis of single neurons and A.N performed all dynamical system modelling.

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August 20, 2023
December 22, 2023