Intranasal dopamine stabilizes prefrontal cortical CaMKIIα-positive neuronal population dynamics during object discrimination
7 affiliations
- 1Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, 100233 Taiwan
- 2Department of Biomedical Sciences, University of Minnesota Medical School, Duluth, MN 55812 USA
- 3Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455 USA
- 4Department of Psychology, Federal University of Paraíba, João Pessoa, 58051 Brazil
- 5Clinic of Nuclear Medicine, University Hospital Düsseldorf, Heinrich Heine University of Düsseldorf, 40225 Düsseldorf, Germany
- 6Center for Behavioral Neuroscience, Heinrich Heine University of Düsseldorf, 40225 Düsseldorf, Germany
- 7Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455 USA
Abstract
Dopamine (DA) is a key modulator of prefrontal cortex function, yet how distinct dopaminergic states shape the temporal organization of cortical population activity during behavior remains poorly understood. We combined in vivo fiber photometry of dorsomedial prefrontal cortex (dmPFC) putative glutamatergic neurons with an object-based attention (OBAT) task in male mice to examine this question. Intranasal DA (IN-DA), which accesses the brain directly via nose-to-brain pathways, left locomotion and exploratory behavior unchanged. Although both vehicle- and IN-DA- treated mice showed a preference for the novel object, this preference reached statistical significance only in the IN-DA group. IN-DA selectively amplified calcium activity within the familiar-object zone and enhanced movement-normalized calcium spike rates. Strikingly, IN-DA reduced both the mean and variability of calcium transient intervals, reflecting a shift toward more frequent and temporally regular events during object processing. To model the network consequences of supraphysiological dopaminergic drive, we administered the psychostimulant amphetamine as a proxy for dopaminergic excess. In contrast to the stabilizing effects of IN-DA, amphetamine induced locomotor hyperactivity accompanied by a collapse of temporal structure, characterized by prolonged inter-transient intervals and markedly increased variability. Together, these findings demonstrate that dopaminergic modulation shapes not only the magnitude but also the temporal organization of dmPFC population activity. At the network level, physiological DA promotes a temporally stable prefrontal state, whereas dopaminergic excess destabilizes it. This provides population-level evidence for the inverted-U relationship between DA signaling and prefrontal function.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1038/s41598-026-65870-1.
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BibTeX
@article{chao2026intranasal,
title = {{Intranasal dopamine stabilizes prefrontal cortical CaMKIIα-positive neuronal population dynamics during object discrimination}},
author = {Owen Y. Chao and Ezequiel Marron Fernandez de Velasco and Flávio Freitas Barbosa and Susanne Nikolaus and Joseph P. Huston and Yi-Mei Yang},
journal = {Scientific Reports},
year = {2026},
month = aug,
doi = {10.1038/s41598-026-65870-1},
url = {https://doi.org/10.1038/s41598-026-65870-1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Intranasal dopamine stabilizes prefrontal cortical CaMKIIα-positive neuronal population dynamics during object discrimination
AU - Owen Y. Chao
AU - Ezequiel Marron Fernandez de Velasco
AU - Flávio Freitas Barbosa
AU - Susanne Nikolaus
AU - Joseph P. Huston
AU - Yi-Mei Yang
PY - 2026
DA - 2026/08/06
JO - Scientific Reports
DO - 10.1038/s41598-026-65870-1
UR - https://doi.org/10.1038/s41598-026-65870-1
AB - Dopamine (DA) is a key modulator of prefrontal cortex function, yet how distinct dopaminergic states shape the temporal organization of cortical population activity during behavior remains poorly understood. We combined in vivo fiber photometry of dorsomedial prefrontal cortex (dmPFC) putative glutamatergic neurons with an object-based attention (OBAT) task in male mice to examine this question. Intranasal DA (IN-DA), which accesses the brain directly via nose-to-brain pathways, left locomotion and exploratory behavior unchanged. Although both vehicle- and IN-DA- treated mice showed a preference for the novel object, this preference reached statistical significance only in the IN-DA group. IN-DA selectively amplified calcium activity within the familiar-object zone and enhanced movement-normalized calcium spike rates. Strikingly, IN-DA reduced both the mean and variability of calcium transient intervals, reflecting a shift toward more frequent and temporally regular events during object processing. To model the network consequences of supraphysiological dopaminergic drive, we administered the psychostimulant amphetamine as a proxy for dopaminergic excess. In contrast to the stabilizing effects of IN-DA, amphetamine induced locomotor hyperactivity accompanied by a collapse of temporal structure, characterized by prolonged inter-transient intervals and markedly increased variability. Together, these findings demonstrate that dopaminergic modulation shapes not only the magnitude but also the temporal organization of dmPFC population activity. At the network level, physiological DA promotes a temporally stable prefrontal state, whereas dopaminergic excess destabilizes it. This provides population-level evidence for the inverted-U relationship between DA signaling and prefrontal function. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1038/s41598-026-65870-1.
SN - 2045-2322
ER -