The estrous cycle modulates hippocampal spine dynamics, dendritic processing, and spatial coding

doi:10.1016/j.neuron.2025.04.014

. 2025 Jul 23;113(14):2297-2309.e7.

doi: 10.1016/j.neuron.2025.04.014. Epub 2025 May 13.

The estrous cycle modulates hippocampal spine dynamics, dendritic processing, and spatial coding

Nora S Wolcott¹, William T Redman², Marie Karpinska³, Emily G Jacobs⁴, Michael J Goard⁵

Affiliations

¹ Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
² Interdepartmental Graduate Program in Dynamical Neuroscience, University of California, Santa Barbara, Santa Barbara, CA 93106, USA; Intelligent Systems Center, Johns Hopkins University Applied Physics Laboratory, Laurel, MD 20723, USA.
³ Department of Computer Science, University of California, Santa Barbara, Santa Barbara, CA 93106, USA; Department of Psychological & Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
⁴ Department of Psychological & Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA 93106, USA; Ann S. Bowers Women's Brain Health Initiative, University of California, Santa Barbara, Santa Barbara, CA 93106, USA; Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
⁵ Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA; Department of Psychological & Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA 93106, USA; Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA 93106, USA. Electronic address: michaelgoard@ucsb.edu.

PMID: 40367943
PMCID: PMC12289434 (available on 2026-05-13)
DOI: 10.1016/j.neuron.2025.04.014

The estrous cycle modulates hippocampal spine dynamics, dendritic processing, and spatial coding

Nora S Wolcott et al. Neuron. 2025.

. 2025 Jul 23;113(14):2297-2309.e7.

doi: 10.1016/j.neuron.2025.04.014. Epub 2025 May 13.

Authors

Nora S Wolcott¹, William T Redman², Marie Karpinska³, Emily G Jacobs⁴, Michael J Goard⁵

Affiliations

¹ Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
² Interdepartmental Graduate Program in Dynamical Neuroscience, University of California, Santa Barbara, Santa Barbara, CA 93106, USA; Intelligent Systems Center, Johns Hopkins University Applied Physics Laboratory, Laurel, MD 20723, USA.
³ Department of Computer Science, University of California, Santa Barbara, Santa Barbara, CA 93106, USA; Department of Psychological & Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
⁴ Department of Psychological & Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA 93106, USA; Ann S. Bowers Women's Brain Health Initiative, University of California, Santa Barbara, Santa Barbara, CA 93106, USA; Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
⁵ Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA; Department of Psychological & Brain Sciences, University of California, Santa Barbara, Santa Barbara, CA 93106, USA; Neuroscience Research Institute, University of California, Santa Barbara, Santa Barbara, CA 93106, USA. Electronic address: michaelgoard@ucsb.edu.

PMID: 40367943
PMCID: PMC12289434 (available on 2026-05-13)
DOI: 10.1016/j.neuron.2025.04.014

Abstract

Histological evidence suggests that the estrous cycle exerts a powerful influence on CA1 neurons in the mammalian hippocampus. Decades have passed since this landmark observation, yet how the estrous cycle shapes dendritic spine dynamics and hippocampal spatial coding in vivo remains a mystery. Here, we used a custom hippocampal microperiscope and two-photon calcium imaging to track CA1 pyramidal neurons in female mice across multiple cycles. Estrous cycle stage had a potent effect on spine dynamics, with spine density peaking during proestrus when estradiol levels are highest. These morphological changes coincided with greater somatodendritic coupling and increased infiltration of back-propagating action potentials into the apical dendrite. Finally, tracking CA1 response properties during navigation revealed greater place field stability during proestrus, evident at both the single-cell and population levels. These findings demonstrate that the estrous cycle drives large-scale structural and functional plasticity in hippocampal neurons essential for learning and memory.

Keywords: dendritic integration; estradiol; estrous cycle; hippocampus; multiphoton imaging; neuroendocrine; place cells; spine morphology.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Update of

The estrous cycle modulates hippocampal spine dynamics, dendritic processing, and spatial coding.
Wolcott NS, Redman WT, Karpinska M, Jacobs EG, Goard MJ. Wolcott NS, et al. bioRxiv [Preprint]. 2024 Aug 3:2024.08.02.606418. doi: 10.1101/2024.08.02.606418. bioRxiv. 2024. Update in: Neuron. 2025 Jul 23;113(14):2297-2309.e7. doi: 10.1016/j.neuron.2025.04.014. PMID: 39131375 Free PMC article. Updated. Preprint.

References

1. Taxier LR, Gross KS & Frick KM (2020). Oestradiol as a neuromodulator of learning and memory. Nat. Rev. Neurosci 21, 535–550. 10.1038/s41583-020-0362-7. - DOI - PMC - PubMed
1. Brinton RD et al. (2008). Progesterone receptors: Form and function in brain. Front. Neuroendocrinol 29, 313–339. 10.1016/j.yfrne.2008.02.001. - DOI - PMC - PubMed
1. McEwen B et al. (2001). Tracking the estrogen receptor in neurons: Implications for estrogen-induced synapse formation. Proc. Natl. Acad. Sci 98, 7093–7100. 10.1073/pnas.121146898. - DOI - PMC - PubMed
1. O’Keefe J & Nadel L (1978). The Hippocampus as a Cognitive Map. (Clarendon Press; Oxford University Press; ).
1. Nieh EH et al. (2021). Geometry of abstract learned knowledge in the hippocampus. Nature 595, 80–84. 10.1038/s41586-021-03652-7. - DOI - PMC - PubMed

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[1] Taxier LR, Gross KS & Frick KM (2020). Oestradiol as a neuromodulator of learning and memory. Nat. Rev. Neurosci 21, 535–550. 10.1038/s41583-020-0362-7. - DOI - PMC - PubMed

[2] Taxier LR, Gross KS & Frick KM (2020). Oestradiol as a neuromodulator of learning and memory. Nat. Rev. Neurosci 21, 535–550. 10.1038/s41583-020-0362-7. - DOI - PMC - PubMed

[3] Brinton RD et al. (2008). Progesterone receptors: Form and function in brain. Front. Neuroendocrinol 29, 313–339. 10.1016/j.yfrne.2008.02.001. - DOI - PMC - PubMed

[4] Brinton RD et al. (2008). Progesterone receptors: Form and function in brain. Front. Neuroendocrinol 29, 313–339. 10.1016/j.yfrne.2008.02.001. - DOI - PMC - PubMed

[5] McEwen B et al. (2001). Tracking the estrogen receptor in neurons: Implications for estrogen-induced synapse formation. Proc. Natl. Acad. Sci 98, 7093–7100. 10.1073/pnas.121146898. - DOI - PMC - PubMed

[6] McEwen B et al. (2001). Tracking the estrogen receptor in neurons: Implications for estrogen-induced synapse formation. Proc. Natl. Acad. Sci 98, 7093–7100. 10.1073/pnas.121146898. - DOI - PMC - PubMed

[7] O’Keefe J & Nadel L (1978). The Hippocampus as a Cognitive Map. (Clarendon Press; Oxford University Press; ).

[8] O’Keefe J & Nadel L (1978). The Hippocampus as a Cognitive Map. (Clarendon Press; Oxford University Press; ).

[9] Nieh EH et al. (2021). Geometry of abstract learned knowledge in the hippocampus. Nature 595, 80–84. 10.1038/s41586-021-03652-7. - DOI - PMC - PubMed

[10] Nieh EH et al. (2021). Geometry of abstract learned knowledge in the hippocampus. Nature 595, 80–84. 10.1038/s41586-021-03652-7. - DOI - PMC - PubMed

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The estrous cycle modulates hippocampal spine dynamics, dendritic processing, and spatial coding

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The estrous cycle modulates hippocampal spine dynamics, dendritic processing, and spatial coding

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Affiliations

Abstract

Conflict of interest statement

Update of

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MeSH terms

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