Journal article
Perinatal serotonin signalling dynamically influences the development of cortical GABAergic circuits with consequences for lifelong sensory encoding
- Abstract:
- Serotonin plays a prominent role in neurodevelopment, regulating processes from cell division to synaptic connectivity. Clinical studies suggest that alterations in serotonin signalling such as genetic polymorphisms or antidepressant exposure during pregnancy are risk factors for neurodevelopmental disorders. However, an understanding of how dysfunctional neuromodulation alters systems level activity over neocortical development is lacking. Here, we use a longitudinal imaging approach to investigate how genetics, pharmacology, and aversive experience disrupt state-dependent serotonin signalling with pathological consequences for sensory processing. We find that all three factors lead to increased neocortical serotonin levels during the initial postnatal period. Genetic deletion of the serotonin transporter or antidepressant dosing results in a switch from hypo- to hyper-cortical activity that arises as a consequence of altered cortical GABAergic microcircuitry. However, the trajectories of these manipulations differ with postnatal exposure to antidepressants having effects on adult sensory encoding. The latter is not seen in the genetic model despite a similar early phenotype, and a distinct influence of maternal genotype on the development of supragranular layers. These results reveal the dynamics and critical nature of serotonin signalling during perinatal life; pharmacological targeting of which can have profound life-long consequences for cognitive development of the offspring.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 6.9MB, Terms of use)
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- Publisher copy:
- 10.1038/s41467-025-59659-5
Authors
- Publisher:
- Springer Nature
- Journal:
- Nature Communications More from this journal
- Volume:
- 16
- Issue:
- 1
- Article number:
- 5203
- Publication date:
- 2025-06-04
- Acceptance date:
- 2025-04-24
- DOI:
- EISSN:
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2041-1723
- Language:
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English
- Pubs id:
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2119654
- Local pid:
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pubs:2119654
- Deposit date:
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2025-04-24
- ARK identifier:
Terms of use
- Copyright holder:
- Ocana-Santero et al
- Copyright date:
- 2025
- Rights statement:
- ©The Author(s) 2025. 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/.
- Notes:
- This work is related to the thesis The role of 5-HT dynamics in cortical population activity throughout mammalian life.
- Licence:
- CC Attribution (CC BY)
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