# Neural Basis of Light-dependent Depression and Anxiety

> **NIH NIH R01** · MICHIGAN STATE UNIVERSITY · 2020 · $379,940

## Abstract

Seasonal affective disorder (SAD) is a major depressive disorder affecting millions of Americans, who suffer
recurring symptoms of depression and anxiety in the winter. Empirical evidence suggests that the
depressive episodes are caused by insufficient light exposure during the winter months, but how changes in
environmental lighting conditions lead to fluctuations in affective state remains largely unknown. This gap in
knowledge presents an important problem for successfully identifying risk factors and biological diagnostic
markers for SAD, as well as for developing more effective therapeutic strategies. The long-term goal of this
research is to understand the brain mechanisms mediating the effects of light on mood and anxiety. The
objective of the proposed work is to identify the role of central orexinergic pathways in mediating light-
dependent fluctuations in affective state. The proposed work will utilize the diurnal grass rat (Arvichantis
niloticus), an animal model of SAD recently developed in the PI's group. There are substantial differences
between nocturnal and diurnal species in their circadian rhythms and central responses to light. Therefore,
a diurnal model is of crucial importance for elucidating the fundamental mechanisms critically underlying
SAD in the diurnal human. The central hypothesis to be tested in this proposal is that light regulates mood
and anxiety by acting on brain pathways containing the neuropeptide, orexin. Using the grass rat model of
SAD, the proposed work contains three Specific Aims: 1) To determine the effects of light on orexin and its
receptors in the diurnal grass rat model of SAD, 2) To test the hypothesis that bright light alleviates
depression- and anxiety-like behaviors via enhancing the orexinergic pathways in the diurnal grass rats, and
3) To identify the downstream targets of orexinergic pathways in alleviating depression- and anxiety-like
behaviors with a focus on the 5-HTergic dorsal raphe. The project is innovative because it utilizes a novel
diurnal animal model and a multi-method approach including cutting-edge molecular biology techniques i.e.
AAV-shRNA, to test a novel hypothesis that the orexinergic system mediates the effects of light on mood
and anxiety. The proposed work is significant because it is expected to advance and expand understanding
of how changes in environmental lighting conditions produce fluctuations in mood and anxiety, which has
the potential to translate into better understanding of the neuropathology underlying SAD in humans.
Ultimately, such knowledge will contribute to the development of novel preventive and therapeutic strategies
for SAD and other mood disorders.

## Key facts

- **NIH application ID:** 9984843
- **Project number:** 5R01MH111276-05
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** Joseph S Lonstein
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $379,940
- **Award type:** 5
- **Project period:** 2016-09-19 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984843

## Citation

> US National Institutes of Health, RePORTER application 9984843, Neural Basis of Light-dependent Depression and Anxiety (5R01MH111276-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9984843. Licensed CC0.

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