Neuromodulatory control of cortical function: Cell-type-specific regulation of neuronal information transfer
4 affiliations
- 1Department of Neurophysics, Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, 6525 AJ, The Netherlands
- 2Netherlands eScience Center, Amsterdam, Noord-Holland, 1098 XH, The Netherlands
- 3Georgia Tech-CNRS IRL 2958, Georgia Institute of Technology-Europe, Metz 57070, France
- 4Department of Psychology, Georgia Institute of Technology, Atlanta, GA 30332
Abstract
Neuromodulatory systems such as dopamine and acetylcholine enable cortical circuits to rapidly shift between behavioral states, yet it remains unclear how receptor-specific signaling reshapes what single neurons compute. Here, we combined whole-cell recordings from excitatory and inhibitory neurons in layer 2/3 of mouse somatosensory cortex with information-theoretic analyses under frozen-noise stimulation. We quantified stimulus-to-spike information transfer and profiled each neuron across four functional domains: passive membrane biophysics, action potential dynamics, intrinsic adaptation currents, and input feature selectivity captured by spike-triggered averages. Activation of D1, D2, or M1 receptors revealed three main findings. First, neuromodulators altered fractional information and firing output in a cell-type- and receptor-specific manner, demonstrating selective regulation of encoding. Second, unsupervised clustering based on functional attribute sets showed that receptor activation reorganizes baseline functional grouping, consistent with a dynamic computational phenotype. Third, multiset correlation and factor analysis revealed that neuromodulation systematically reorganizes covariance among functional domains. In excitatory neurons, dopaminergic activation decreased coordination between input feature selectivity and other functional properties while strengthening coordination among response-based features such as spike dynamics and adaptation. Inhibitory neurons, by contrast, generally exhibited increased coordination across domains. In unison, these findings identify neuromodulation as a reconfiguration signal that reshapes not only individual cellular properties, but also the statistical architecture linking them across the recorded cohort, thereby revealing a higher-dimensional mode of single-neuron regulatory control in the cortex.
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BibTeX
@article{joshi2026neuromodulatory,
title = {{Neuromodulatory control of cortical function: Cell-type-specific regulation of neuronal information transfer}},
author = {Nishant Joshi and Xuan Yan and Niccoló Calcini and Payam Safavi and Asli Ak and Koen Kole and Sven van der Burg and Tansu Celikel and Fleur Zeldenrust},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
year = {2026},
month = oct,
doi = {10.1073/pnas.2609893123},
url = {https://doi.org/10.1073/pnas.2609893123},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Neuromodulatory control of cortical function: Cell-type-specific regulation of neuronal information transfer
AU - Nishant Joshi
AU - Xuan Yan
AU - Niccoló Calcini
AU - Payam Safavi
AU - Asli Ak
AU - Koen Kole
AU - Sven van der Burg
AU - Tansu Celikel
AU - Fleur Zeldenrust
PY - 2026
DA - 2026/10/19
JO - Proceedings of the National Academy of Sciences of the United States of America
DO - 10.1073/pnas.2609893123
UR - https://doi.org/10.1073/pnas.2609893123
AB - Neuromodulatory systems such as dopamine and acetylcholine enable cortical circuits to rapidly shift between behavioral states, yet it remains unclear how receptor-specific signaling reshapes what single neurons compute. Here, we combined whole-cell recordings from excitatory and inhibitory neurons in layer 2/3 of mouse somatosensory cortex with information-theoretic analyses under frozen-noise stimulation. We quantified stimulus-to-spike information transfer and profiled each neuron across four functional domains: passive membrane biophysics, action potential dynamics, intrinsic adaptation currents, and input feature selectivity captured by spike-triggered averages. Activation of D1, D2, or M1 receptors revealed three main findings. First, neuromodulators altered fractional information and firing output in a cell-type- and receptor-specific manner, demonstrating selective regulation of encoding. Second, unsupervised clustering based on functional attribute sets showed that receptor activation reorganizes baseline functional grouping, consistent with a dynamic computational phenotype. Third, multiset correlation and factor analysis revealed that neuromodulation systematically reorganizes covariance among functional domains. In excitatory neurons, dopaminergic activation decreased coordination between input feature selectivity and other functional properties while strengthening coordination among response-based features such as spike dynamics and adaptation. Inhibitory neurons, by contrast, generally exhibited increased coordination across domains. In unison, these findings identify neuromodulation as a reconfiguration signal that reshapes not only individual cellular properties, but also the statistical architecture linking them across the recorded cohort, thereby revealing a higher-dimensional mode of single-neuron regulatory control in the cortex.
SN - 0027-8424
SN - 1091-6490
ER -