# The role of the locus coeruleus in mediating pupil-linked arousal

> **NIH NIH R01** · COLUMBIA UNIV NEW YORK MORNINGSIDE · 2020 · $394,905

## Abstract

The role of the locus coeruleus in mediating pupil-linked arousal
Non-luminance-mediated changes in pupil size have been widely used to index state of arousal in rodents,
non-human primates, and humans. Individuals with neuropsychiatric disorders exhibit atypical task-evoked
pupil dilation during cognitive tasks. However, the underlying mechanism which couples arousal and pupil size
remains unclear. This limits the use of pupillometry in studies of state dependent neural computation and
behavior in the healthy brain, and as a tool to infer the pathological dynamics of neuromodulatory processes in
the diseased brain. It has long been postulated that the locus coeruleus (LC) mediates the tight correlation
between arousal and non-luminance-mediated changes in pupil size during cognitive tasks. However, due to
the small size and location of the LC, there is no direct experimental evidence to support this hypothesis. Using
a combination of electrophysiology, optogenetic activation/silencing technology, pupillometry, and behavior
tasks, we are uniquely positioned to test this hypothesis. In this project, we will 1) determine the modulatory
effect of LC activation on pupil size, 2) elucidate the modulatory effect of LC activation on cognitive factors and
behavioral performance of head-fixed rats performing tactile detection tasks, and 3) determine the extent to
which the LC mediates the correction between changes in pupil size and arousal/behavior by optogenetically
silencing the LC. Significance: Human and animal studies have shown that nonluminance-mediated changes
in pupil size are tightly correlated with many factors varying along with the dimension of arousal. It has long
been posited that task-evoked changes in pupil size during cognitive tasks are modulated by the LC. However,
the precise link between LC activity, change in pupil size, arousal and behavioral performance remains little
understood. The success of our aims will advance our understanding of how the LC modulates arousal and
pupil size simultaneously, allowing us to precisely interpret pupillometry in many cognitive tasks and clinical
settings. Innovation: We will use a novel combination of experimental techniques, including pupillometry,
optogenetic perturbation, electrophysiology, and behavioral tasks, to address the role of the locus coeruleus in
mediating the correlation between changes in pupil size and arousal/behavior. Moreover, we will develop a
novel model to infer LC activation from pupillometry.

## Key facts

- **NIH application ID:** 9824585
- **Project number:** 5R01MH112267-04
- **Recipient organization:** COLUMBIA UNIV NEW YORK MORNINGSIDE
- **Principal Investigator:** Qi Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $394,905
- **Award type:** 5
- **Project period:** 2016-12-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9824585

## Citation

> US National Institutes of Health, RePORTER application 9824585, The role of the locus coeruleus in mediating pupil-linked arousal (5R01MH112267-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9824585. Licensed CC0.

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