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Quantitative anatomy and biophysical modeling of ascending neuromodulatory systems in the developing rat neocortex

Lookup NU author(s): Dr Srikanth RamaswamyORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2026 Colangelo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. http://creativecommons.org/licenses/by/4.0/ The hindlimb representation in the somatosensory cortex of two-week old Wistar rats has been a valuable model system for dissecting the microcircuitry of neurons and their synaptic connections. In this study, we present a comprehensive experimental dataset quantifying the fiber length per cortical volume and the density of varicosities for cholinergic, catecholaminergic, and serotonergic neuromodulatory systems within the cortical neuropil using immunocytochemical staining and stereological techniques, along with a methodological framework for generating biophysically detailed computational models from these data. Acquired data were integrated into a biophysically detailed computational model of the somatosensory cortex to explore the anatomical organization and functional implications of neuromodulatory innervation. We found that neuromodulatory innervation, although sparse, substantially impacts network activity. Network simulations support the hypothesis that acetylcholine suppresses slow oscillations and promotes the desynchronization of cortical networks, consistent with the extensive findings in existing literature. Additionally, the temporal properties of acetylcholine modulation are consistent with synaptic rather than volume release. Furthermore, we found that the release of dopamine and serotonin in sensory cortices induces network desynchronization by inhibiting delta oscillations and that serotonin also initiates the emergence of theta oscillations, pointing to previously unexplored aspects of their function in governing cortical network activity. The experimental data and the biophysical computational model are available as an open-access community resource.

Publication metadata

Author(s): Colangelo C, Munoz A, Antonietti A, Sood V, Anton-Fernandez A, Herttuainen J, Romani A, DeFelipe J, Ramaswamy S

Publication type: Article

Publication status: Published

Journal: PLoS Computational Biology

Year: 2026

Volume: 22

Issue: 6

Online publication date: 26/06/2026

Acceptance date: 15/06/2026

Date deposited: 20/07/2026

ISSN (electronic): 1553-7358

Publisher: Public Library of Science

URL: https://doi.org/10.1371/journal.pcbi.1014460

DOI: 10.1371/journal.pcbi.1014460

Data Access Statement: Data on varicosity densities of neuromodulatory inputs are reported in figures and text in this publication and deposited at Zenodo (https://doi.org/10.5281/zenodo.14587678). Volumetric atlases, neuron reconstructions, the parameterization of connectivity in JSON format, and the description of the model in SONATA format have been deposited at Zenodo and are publicly available as of the data of the publication. Original code has been deposited at Zenodo and is publicly available at https://doi.org/10.5281/zenodo.14587678.

PubMed id: 42361121

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