Encoding of female mating dynamics by a hypothalamic line attractor
Creators
-
1.
California Institute of Technology
-
2.
Howard Hughes Medical Institute
-
3.
Stanford University
Abstract
Females exhibit complex, dynamic behaviours during mating with variable sexual receptivity depending on hormonal status1,2,3,4. However, how their brains encode the dynamics of mating and receptivity remains largely unknown. The ventromedial hypothalamus, ventrolateral subdivision contains oestrogen receptor type 1-positive neurons that control mating receptivity in female mice5,6. Here, unsupervised dynamical system analysis of calcium imaging data from these neurons during mating uncovered a dimension with slow ramping activity, generating a line attractor in neural state space. Neural perturbations in behaving females demonstrated relaxation of population activity back into the attractor. During mating, population activity integrated male cues to ramp up along this attractor, peaking just before ejaculation. Activity in the attractor dimension was positively correlated with the degree of receptivity. Longitudinal imaging revealed that attractor dynamics appear and disappear across the oestrus cycle and are hormone dependent. These observations suggest that a hypothalamic line attractor encodes a persistent, escalating state of female sexual arousal or drive during mating. They also demonstrate that attractors can be reversibly modulated by hormonal status, on a timescale of days.
Copyright and License
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/.
Acknowledgement
We thank A. Kennedy for critical feedback on the manuscript; Y. Huang for genotyping; G. Mancuso and L. Chavarria for administrative assistance; C. Chiu for laboratory management; E. Carcamo for mouse colony management; the Caltech OLAR staff for animal care; and members of the Anderson Laboratory for helpful comments on this project. D.J.A. is an investigator of the Howard Hughes Medical Institute. This work was supported by grants from the NIH (RO1MH112593, RO1MH123612 and RO1NS123916). A.N. is supported by a National Science Scholarship from the Agency of Science, Technology and Research, Singapore.
Funding
D.J.A. is an investigator of the Howard Hughes Medical Institute. This work was supported by grants from the NIH (RO1MH112593, RO1MH123612 and RO1NS123916). A.N. is supported by a National Science Scholarship from the Agency of Science, Technology and Research, Singapore.
Contributions
These authors contributed equally: Mengyu Liu, Aditya Nair.
D.J.A., M.L. and A.N. conceptualized the study. M.L. conducted the experiments. M.L., A.N., N.C. and S.W.L. performed the data analysis. D.J.A. supervised the study. D.J.A., M.L., A.N. and S.W.L. wrote the manuscript.
Data Availability
Data pertaining to this Article have been deposited in the DANDI repository with the accession code 001097.
Code Availability
The code to analyse the rSLDS models is available at GitHub (https://github.com/lindermanlab/ssm). The rSLDS model weights and parameters have also been deposited in the DANDI with the accession code 001097.
Conflict of Interest
The authors declare no competing interests.
Errata
15 September 2025: This paper was originally published under Creative Commons Attribution 4.0 International license, CC-BY-NC-ND, © The Author(s). It is now available under a Creative Commons Attribution 4.0 International license, CC-BY, © The Author(s). The error has been corrected in the online version of the article.
Supplemental Material
Mating assay with intromission behaviour and high sexual receptivity in female mice. Mating assay where the female mouse exhibits high sexual receptivity which is accompanied by intromission behaviour by the male mouse.
Mating assay with intromission behaviour and low sexual receptivity in female mice. Mating assay where the female mouse exhibits low sexual receptivity which is accompanied by intromission behaviour by the male mouse.
Extended Data Fig. 1 Behavior dynamics and neural responses to conspecific sex
Extended Data Fig. 2 Neural tuning to conspecific sex and behavior
Extended Data Fig. 3 Additional example trials with rSLDS model fit, additional information for Fig. 3
Extended Data Fig. 4 Dynamics of single cell activity
Extended Data Fig. 5 Independent verification and neural perturbations of line attractor dynamics
Extended Data Fig. 6 Line attractor dynamics across the estrus cycle
Extended Data Fig. 7 Single cell persistence at receptive and unreceptive days
Extended Data Fig. 8 Mechanistic model for loss of line attractor dynamics in unreceptive states
Extended Data Fig. 9 Population dynamics before and after OVX in the same female
Extended Data Fig. 10 Longitudinal mating assay and correlation with attractor dynamics
Files
s41586-024-07916-w.pdf
Files
(157.7 MB)
| Name | Size | Download all |
|---|---|---|
|
md5:dee1d9ab0116582019e3b5eaaebaf4e6
|
77.5 MB | Download |
|
md5:b1552c5d09dd65784404341bcb859be6
|
65.1 MB | Download |
|
md5:44459361b8e7c73c7297f8b8bd798432
|
15.0 MB | Preview Download |
Additional details
Identifiers
- PMCID
- PMC11499253
- PMID
- 39142338
Related works
- Describes
- Journal Article: https://rdcu.be/eVwe5 (ReadCube)
- Journal Article: PMC11499253 (PMCID)
- Journal Article: 39142338 (PMID)
- Is supplemented by
- Dataset: 10.48324/dandi.001097/0.240814.1849 (DOI)
Funding
- National Institutes of Health
- RO1MH112593
- National Institutes of Health
- RO1MH123612
- National Institutes of Health
- RO1NS123916
- Agency for Science, Technology and Research
Dates
- Submitted
-
2023-03-30
- Accepted
-
2024-08-06
- Available
-
2024-08-14Published
- Available
-
2024-09-18Version of record