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Pupil-linked arousal heterogeneously modulates cell-type-specific sensory processing.

Overview

Authors: Keith J Kaufman1,2,3, Rebecca F Krall1,2, Ross S Williamson1,2,3,4,5
ORCID iDs: Keith J Kaufman, Rebecca F Krall, Ross S Williamson
  1. Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, USA
  2. Pittsburgh Hearing Research Center, University of Pittsburgh, Pittsburgh, PA, USA
  3. Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA, USA
  4. Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA
  5. Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA
Institutions: University of Pittsburgh (United States); Center for the Neural Basis of Cognition (United States)
Journal: Science advances, volume 12, issue 14, article eadz6495
Dates: received 9 June 2025; accepted 3 March 2026; published online 3 April 2026; in print April 2026
Type: Research article · Language: English
License: CC BY-NC
Identifiers: DOI 10.1126/sciadv.adz6495 · PMID 41931609 · PMCID PMC13048257 · OpenAlex W7148922695
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: mouse (organism), systems (subfield)
Methods: Connectivity, Statistics, Smoothing, state filtering, decompositions, Machine learning, Preprocessing, fMRI & imaging, Single-unit activity, calcium imaging, Physiology & signal measures
MeSH: Arousal*, Auditory Cortex*, Neurons*, Pupil*, Animals, Male, Mice (* major topic)
Topic: Neural dynamics and brain function (Cognitive Neuroscience, Neuroscience), according to OpenAlex
Funding: National Institutes of Health (T32DC011499, R21DC018327, F31DC021867, R01DC020459); Klingenstein-Simons Fellowship in Neuroscience; NIDCD NIH HHS (F31 DC021867); Hearing Health Foundation
Citations: cited by 3 papers (Europe PMC); 144 references in the paper

Abstract

Arousal is a ubiquitous influence on the brain. It affects membrane potentials, cortical state, and sensory encoding, yet how arousal influences distinct excitatory cell types in neocortex remains poorly understood. To test this, we combined two-photon calcium imaging and pupillometry in awake mice to examine arousal-related activity in excitatory subpopulations of auditory cortex: intratelencephalic (IT), extratelencephalic (ET), and corticothalamic (CT) neurons. We observed substantial within-group variability alongside significant cell-type–specific differences, suggesting that arousal exerts a widespread but heterogeneous influence on cortical excitatory networks. Pupil-linked arousal modulated subtypes through linear and nonlinear response motifs. ET neurons exhibited predominantly multiplicative and additive gain modulations, with enhanced response magnitude and stimulus encoding but reduced frequency selectivity. CT and layer 2/3 neurons showed inverted-U relationships between arousal and response strength and decoding accuracy, whereas IT neurons were minimally affected. These effects tracked changes in population-level reliability, revealing a mechanistic link between internal state and representational stability.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Code

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The paper's code and data availability statement is in the Data section.

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Data

Datasets cited

Data, code, and materials availability

All data and code needed to evaluate and reproduce the results in the paper are present in the paper and/or the Supplementary Materials and are available from https://doi.org/10.5281/zenodo.18282596. No new materials were generated by this study.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Versions

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Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 3 authors, 7 MeSH terms, 4 funders, 140 references.

Cite

This paper

Kaufman, K. J., Krall, R. F., & Williamson, R. S. (2026). Pupil-linked arousal heterogeneously modulates cell-type-specific sensory processing. Science advances, 12(14), eadz6495. https://doi.org/10.1126/sciadv.adz6495

BibTeX

@article{kaufman2026pupil,
author = {Kaufman, Keith J and Krall, Rebecca F and Williamson, Ross S},
title = {{Pupil-linked arousal heterogeneously modulates cell-type-specific sensory processing}},
journal = {Science advances},
year = {2026},
month = apr,
volume = {12},
number = {14},
pages = {eadz6495},
publisher = {American Association for the Advancement of Science},
issn = {2375-2548},
doi = {10.1126/sciadv.adz6495},
url = {https://doi.org/10.1126/sciadv.adz6495},
pmid = {41931609},
pmcid = {PMC13048257}
}

RIS

TY - JOUR
AU - Kaufman, Keith J
AU - Krall, Rebecca F
AU - Williamson, Ross S
TI - Pupil-linked arousal heterogeneously modulates cell-type-specific sensory processing
T2 - Science advances
J2 - Sci Adv
PY - 2026
DA - 2026/04/03
VL - 12
IS - 14
SP - eadz6495
SN - 2375-2548
PB - American Association for the Advancement of Science
DO - 10.1126/sciadv.adz6495
UR - https://doi.org/10.1126/sciadv.adz6495
LA - en
ER -

CSL-JSON

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