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Peer-reviewedCC BYFrontiers in molecular neuroscience

Beyond the locus coeruleus: pupil dynamics as a systems-level marker of neuromodulatory influences on hippocampal memory.

  1. 1Andrew Mayes Centre for Cognitive Neuroscience, School of Health Sciences, University of Manchester, Manchester, United Kingdom.

Abstract

Dopamine and norepinephrine regulate hippocampal plasticity through molecular, cellular and circuit mechanisms that shape which experiences are encoded and later remembered. Translating these mechanisms into human memory research remains challenging because direct measures of endogenous catecholaminergic activity are difficult to obtain during memory formation. This Perspective argues that pupillometry provides a non-invasive, temporally precise biomarker for bridging this translational gap. Rather than treating pupil dynamics as a simple proxy for locus coeruleus activity or general arousal, I consider whether pupil-linked memory effects can be better understood by relating them to concurrent neuromodulatory, autonomic and hippocampal processes. I further propose that dilation- and constriction-linked encoding profiles may be associated with different physiological configurations across encoding contexts, including conditions that favour model updating or integration with existing knowledge. I outline how multimodal approaches combining pupillometry with functional MRI, neuromelanin-sensitive imaging, pharmacology, magnetic resonance spectroscopy and computational modelling can test these hypotheses directly. Reframing pupillometry in this way provides a scalable route for linking dopamine and norepinephrine mechanisms with human hippocampal memory and for advancing translational research across ageing and disease.

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BibTeX
@article{kafkas2026beyond,
  title = {{Beyond the locus coeruleus: pupil dynamics as a systems-level marker of neuromodulatory influences on hippocampal memory.}},
  author = {Alex Kafkas},
  journal = {Frontiers in molecular neuroscience},
  year = {2026},
  month = oct,
  doi = {10.3389/fnmol.2026.1976085},
  url = {https://europepmc.org/article/MED/42908963},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Beyond the locus coeruleus: pupil dynamics as a systems-level marker of neuromodulatory influences on hippocampal memory.
AU  - Alex Kafkas
PY  - 2026
DA  - 2026/10/07
JO  - Frontiers in molecular neuroscience
DO  - 10.3389/fnmol.2026.1976085
UR  - https://europepmc.org/article/MED/42908963
AB  - Dopamine and norepinephrine regulate hippocampal plasticity through molecular, cellular and circuit mechanisms that shape which experiences are encoded and later remembered. Translating these mechanisms into human memory research remains challenging because direct measures of endogenous catecholaminergic activity are difficult to obtain during memory formation. This Perspective argues that pupillometry provides a non-invasive, temporally precise biomarker for bridging this translational gap. Rather than treating pupil dynamics as a simple proxy for locus coeruleus activity or general arousal, I consider whether pupil-linked memory effects can be better understood by relating them to concurrent neuromodulatory, autonomic and hippocampal processes. I further propose that dilation- and constriction-linked encoding profiles may be associated with different physiological configurations across encoding contexts, including conditions that favour model updating or integration with existing knowledge. I outline how multimodal approaches combining pupillometry with functional MRI, neuromelanin-sensitive imaging, pharmacology, magnetic resonance spectroscopy and computational modelling can test these hypotheses directly. Reframing pupillometry in this way provides a scalable route for linking dopamine and norepinephrine mechanisms with human hippocampal memory and for advancing translational research across ageing and disease.
SN  - 1662-5099
ER  -