Noradrenaline causes a spread of association in the hippocampal cognitive map

Koolschijn, Renée S.; Parthasarathy, Prakriti; Browning, Michael; Przygodda, Xenia; Capitão, Liliana P.; Clarke, William T.; Vogels, Tim P; O’Reilly, Jill X.; Barron, Helen C.

Noradrenaline causes a spread of association in the hippocampal cognitive map

Koolschijn RS, Parthasarathy P, Browning M, Przygodda X, Capitão LP, Clarke WT, Vogels TP, O’Reilly JX, Barron HC. 2026. Noradrenaline causes a spread of association in the hippocampal cognitive map. Nature Communications. 17, 3961.

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DOI

10.1038/s41467-026-70659-x

Journal Article | Published | English

Scopus indexed

Author

Koolschijn, Renée S.; Parthasarathy, Prakriti; Browning, Michael; Przygodda, Xenia; Capitão, Liliana P.; Clarke, William T.; Vogels, Tim P^ISTA ; O’Reilly, Jill X.; Barron, Helen C.

Department

Vogels Group

Abstract

The mammalian brain organises knowledge about entities in the world and relationships between them using cognitive maps. When forming a cognitive map, there is a necessary trade-off between extending the map to make novel inferences, and storing a veridical copy of past experience. However, the neural mechanisms that control this trade-off remain unknown. Using a cross-scale approach that combines a pharmacological intervention in humans with neural network modelling, we show that the neuromodulator noradrenaline elicits a significant ‘spread of association’ across hippocampal cognitive maps. This neural spread of association can be explained by changes in synaptic plasticity that predict overgeneralisation in behaviour. Thus, elevated noradrenaline during learning increases the ‘smoothing kernel’ for plasticity across the cognitive map, allowing disparate memories to become linked and distorted.

Publishing Year

2026

Date Published

2026-05-01

Journal Title

Nature Communications

Publisher

Springer Nature

Acknowledgement

We would like to thank Chamith Halahakoon, Phil Cowen, Angharad De Cates, Beata Godlewska, Riccardo De Giorgi, Katherine Smith and Edoardo Ostinelli for enabling this study by providing medical cover. We would like to thank Douglas F. Tomé and Everton J. Agnes for their guidance and advice with earlier versions of the neural network model. We would like to thank Rob Froemke for helpful discussion when preparing the experiments. We thank Leonie Glitz and Valentina Mancini for comments on an earlier version of the manuscript. R.S.K. was supported by an EPSRC/MRC-funded studentship (EP/L016052/1). P.P. was supported by the Cambridge Trust, Trinity Henry Barlow Scholarship and Trinity Hall Brockhouse Scholarship. L.C. is supported by the Foundation for Science and Technology (FCT) (Portuguese State Budget: UID/PSI/01662/2020; Research fellowship: 2021.00415.CEECIND). W.T.C. is funded by the Wellcome Trust [225924/Z/22/Z]. H.C.B. is supported by a UKRI Future Leaders Fellowship (MR/W008939/1) and the Wellcome Institutional Strategic Support Fund. H.C.B. and J.X.O. are supported by the Medical Research Council (MR/W01971X/1). The study was supported by the NIHR Oxford Health Biomedical Research Centre (NIHR203316). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. The Wellcome Centre for Integrative Neuroimaging is supported by core funding from the Wellcome Trust (203139/Z/16/Z and 203139/A/16/Z). This research was funded in part by the Wellcome Trust. For the purpose of open access, the author(s) have applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission.

Volume

Article Number

3961

eISSN

2041-1723

IST-REx-ID

21895

Cite this

Koolschijn RS, Parthasarathy P, Browning M, et al. Noradrenaline causes a spread of association in the hippocampal cognitive map. Nature Communications. 2026;17. doi:10.1038/s41467-026-70659-x

Koolschijn, R. S., Parthasarathy, P., Browning, M., Przygodda, X., Capitão, L. P., Clarke, W. T., … Barron, H. C. (2026). Noradrenaline causes a spread of association in the hippocampal cognitive map. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-026-70659-x

Koolschijn, Renée S., Prakriti Parthasarathy, Michael Browning, Xenia Przygodda, Liliana P. Capitão, William T. Clarke, Tim P Vogels, Jill X. O’Reilly, and Helen C. Barron. “Noradrenaline Causes a Spread of Association in the Hippocampal Cognitive Map.” Nature Communications. Springer Nature, 2026. https://doi.org/10.1038/s41467-026-70659-x.

R. S. Koolschijn et al., “Noradrenaline causes a spread of association in the hippocampal cognitive map,” Nature Communications, vol. 17. Springer Nature, 2026.

Koolschijn, Renée S., et al. “Noradrenaline Causes a Spread of Association in the Hippocampal Cognitive Map.” Nature Communications, vol. 17, 3961, Springer Nature, 2026, doi:10.1038/s41467-026-70659-x.

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