Light Affects Mood and Learning through Distinct Retina-Brain Pathways
Open accessAbstract
Light exerts a range of powerful biological effects beyond image vision, including mood and learning regulation. While the source of photic information affecting mood and cognitive functions is well established, viz. intrinsically photosensitive retinal ganglion cells (ipRGCs), the central mediators are unknown. Here, we reveal that the direct effects of light on learning and mood utilize distinct ipRGC output streams. ipRGCs that project to the suprachiasmatic nucleus (SCN) mediate the effects of light on learning, independently of the SCN's pacemaker function. Mood regulation by light, on the other hand, requires an SCN-independent pathway linking ipRGCs to a previously unrecognized thalamic region, termed perihabenular nucleus (PHb). The PHb is integrated in a distinctive circuitry with mood-regulating centers and is both necessary and sufficient for driving the effects of light on affective behavior. Together, these results provide new insights into the neural basis required for light to influence mood and learning.
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Phototherapy plays a significant role in regulating emotional behavior and can have strong and rapid effects on mood and alertness.
“Phototherapy plays a significant role in regulating emotional behavior 399 and can have strong and rapid effects on mood and alertness. 400 – 402”
From Major depressive disorder: hypothesis, mechanism, prevention and treatment (2024) · cites this paper as [399]
The Introduction and Discussion (Perspective; page unavailable) state that light affects mood and that light-mediated pathways regulate affective behavior. They do not establish that phototherapy, as a treatment, regulates emotional behavior. The separate claim about rapid effects on mood and alertness is attached to other citations in the citing sentence. (LLM, conf=0.84)
Experimental — accuracy not yet measuredA pathway from the retina to the habenula has recently been found to be involved in mediating effects of light on mood in animal models.
“In addition to the circadian effects of light mediated via the SCN, a pathway from the retina to the habenula has recently been found to be involved in mediating effects of light on mood in animal models [38, 110].”
From Effects of light on human circadian rhythms, sleep and mood (2019) · cites this paper as [38]
The Introduction and Discussion say that retinal input to the perihabenular nucleus (PHb) mediates light’s effects on mood in mice. The Results identify the PHb as a dorsal thalamic nucleus adjacent to, but distinct from, the lateral habenula. Thus the mood pathway is supported, but describing its target as the habenula is anatomically imprecise. (LLM, conf=0.88)
Experimental — accuracy not yet measuredRecent evidence from animal studies shows that the habenula in the thalamus is innervated by retinal projections which may specifically mediate mood-related non-visual effects of light.
“In addition to the pathway between retina and SCN, there is recent evidence from animal studies showing that also the habenula in the thalamus is innervated by retinal projections [38, 110] which may specifically mediate mood-related non-visual effects of light.”
From Effects of light on human circadian rhythms, sleep and mood (2019) · cites this paper as [38]
The Results (‘PHb neurons receive direct input from ipRGCs’) report retinal input to the perihabenular region (PHb), and the Introduction links that input to light-induced mood changes in mice. But the paper identifies the PHb as a dorsal thalamic region adjacent to the lateral habenula, not the habenula itself; the claim conflates the two. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe retina-to-habenula pathway, connecting some ipRGCs with the habenula and bypassing the SCN, has been suggested to specifically mediate light-induced alterations in mood.
“This pathway, connecting some ipRGCs with the habenula and bypassing the SCN altogether, has been suggested to specifically mediate light-induced alterations in mood [38].”
From Effects of light on human circadian rhythms, sleep and mood (2019) · cites this paper as [38]
The Introduction and Abstract describe an SCN-independent ipRGC pathway that mediates light-induced mood changes. But the Results identify its target as the perihabenular nucleus (PHb), a distinct dorsal thalamic region adjacent to the lateral habenula—not the habenula itself. Page numbers are unavailable in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredMelanopsin (λmax ~480 nm) is expressed in intrinsically photosensitive retinal ganglion cells (ipRGCs) that mediate circadian entrainment, the pupillary light reflex, and light-regulated changes in mood.
“Additionally, melanopsin (λmax ~480 nm) is expressed in intrinsically photosensitive retinal ganglion cells (ipRGCs) that mediate circadian entrainment, the pupillary light reflex, and light-regulated changes in mood (Panda et al., 2003; Hattar et al., 2003; Fernandez et al., 2018).”
From Ventral striatum dopamine release encodes unique properties of visual stimuli in mice (2023) · cites this paper as Fernandez et al., 2018
The Introduction identifies melanopsin-expressing ipRGCs and describes their role in circadian photoentrainment; the Introduction and Discussion also link ipRGCs to light-regulated mood. Our copy does not give melanopsin’s peak wavelength of approximately 480 nm. It mentions the pupillary light reflex only in the title of a cited reference, not in its own discussion or findings. (LLM, conf=0.84)
Experimental — accuracy not yet measured
In mice, light input to the brain reaches neural circuits related to depression and learning through distinct projections from the retina.
“Using mice, this study demonstrates that light input to the brain reaches neural circuits related to depression and learning through distinct projections from the retina, revealing a potential mechanism by which aberrant light exposure (for example, light at night) affects mood and cognition.”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [324]
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Campbell, I., Sharifpour, R., & Vandewalle, G. (2023) · Clocks & Sleep · doi:10.3390/clockssleep5010012 · Cited by 43 · see citing works
Henriksen, T. E. G., Grønli, J., Assmus, J., Fasmer, O. B., Schoeyen, H., Leskauskaite, I., Bjorke‐Bertheussen, J., Ytrehus, K., & Lund, A. (2020) · Journal of Sleep Research · doi:10.1111/jsr.12984 · Cited by 40 · see citing works
Temporal vision: measures, mechanisms and meaning
Donner, K. (2021) · Journal of Experimental Biology · doi:10.1242/jeb.222679 · Cited by 33 · see citing works
Lucas, J. A., & Schmidt, T. M. (2019) · Neural Development · doi:10.1186/s13064-019-0132-2 · Cited by 27 · see citing works
Ventral striatum dopamine release encodes unique properties of visual stimuli in mice
Gonzalez, L. S., Fisher, A. A., D'Souza, S. P., Cotella, E. M., Lang, R. A., & Robinson, J. E. (2023) · eLife · doi:10.7554/elife.85064 · Cited by 18 · see citing works
“85064 9 of 20 pupillary light reflex, and light- regulated changes in mood (Panda et al., 2003; Hattar et al., 2003; Fernandez et al., 2018).”
BackgroundGeoffroy, P. A., Palagini, L., Henriksen, T. E. G., Bourgin, P., Garbazza, C., Gronfier, C., Esaki, Y., Fernandez, D. C., Lam, R. W., Lee, H.-J., et al. (2025) · Dialogues in Clinical Neuroscience · doi:10.1080/19585969.2025.2533806 · Cited by 10 · see citing works
Self-citationViolet Light Modulates the Central Nervous System to Regulate Memory and Mood
Sasaki, N., Gusain, P., Hayano, M., Sugaya, T., Tonegawa, N., Hatanaka, Y., Tamura, R., Okuyama, K., Osada, H., Ban, N., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.11.02.466604 · Cited by 5 · see citing works
- Authors
- Fernandez, D. C., Fogerson, P. M., Lazzerini Ospri, L., Thomsen, M. B., Layne, R. M., Severin, D., Zhan, J., Singer, J. H., Kirkwood, A., Zhao, H., Berson, D. M., & Hattar, S.
- Affiliations
- Johns Hopkins University (US)
- Brown University (US)
- University of Maryland, College Park (US)
- Corresponding author
- Fernandez, Diego Carlos
- Hattar, Samer
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 175
- Issue
- 1
- Pages
- 71-84.e18
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC6190605
- OpenAlex
- W2889400183
- Cited by
- 505
- References
- 70
- Citations by year
- 2026: 55 · 2025: 73 · 2024: 65 · 2023: 72 · 2022: 59 · 2021: 66 · 2020: 73 · 2019: 36 · 2018: 6
- FWCI
- 25.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (GM076430, EY027202, EY012793, EY017137)
- Alcon Research Institute
- PEW Charitable Trusts
- NSF (I2011104359)
- National Institute of Mental Health
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Visual perception and processing mechanisms
- Keywords
- intrinsically photosensitive retinal ganglion cells, suprachiasmatic nucleus, thalamus, circadian pacemaker, emotional behavior, neural circuits
- MeSH terms
- Affect, Animals, Brain, Circadian Rhythm, Learning, Light, Mice, Inbred C57BL, Phototherapy, Retina, Retinal Ganglion Cells, Suprachiasmatic Nucleus, Vision, Ocular, Visual Pathways, Visual Perception, Signal Transduction, Mice
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