Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

The cognitive impact of light: illuminating ipRGC circuit mechanisms

Nature Reviews Neuroscience volume 25, pages 159–175 (2024)Cite this article

Subjects

Abstract

Ever-present in our environments, light entrains circadian rhythms over long timescales, influencing daily activity patterns, health and performance. Increasing evidence indicates that light also acts independently of the circadian system to directly impact physiology and behaviour, including cognition. Exposure to light stimulates brain areas involved in cognition and appears to improve a broad range of cognitive functions. However, the extent of these effects and their mechanisms are unknown. Intrinsically photosensitive retinal ganglion cells (ipRGCs) have emerged as the primary conduit through which light impacts non-image-forming behaviours and are a prime candidate for mediating the direct effects of light on cognition. Here, we review the current state of understanding of these effects in humans and mice, and the tools available to uncover circuit-level and photoreceptor-specific mechanisms. We also address current barriers to progress in this area. Current and future efforts to unravel the circuits through which light influences cognitive functions may inform the tailoring of lighting landscapes to optimize health and cognitive function.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Light entering the retina is transmitted to multiple brain targets by retinal ganglion cells.
Fig. 2: ipRGCs innervate brain areas involved in cognitive circuits.
Fig. 3: Known and potential roles for ipRGC input to neuromodulatory systems.
Fig. 4: Tools for dissecting cognitive ipRGC circuits in mice.

Similar content being viewed by others

References

  1. Yalçin, M. et al. It’s about time: the circadian network as time-keeper for cognitive functioning, locomotor activity and mental health. Front. Physiol. 13, 873237 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  2. Muscogiuri, G. et al. Exposure to artificial light at night: a common link for obesity and cancer? Eur. J. Cancer 173, 263–275 (2022).

    Article  PubMed  Google Scholar 

  3. Dollish, H. K., Tsyglakova, M. & McClung, C. A. Circadian rhythms and mood disorders: time to see the light. Neuron https://doi.org/10.1016/j.neuron.2023.09.023 (2023).

  4. Zielinska-Dabkowska, K. M., Schernhammer, E. S., Hanifin, J. P. & Brainard, G. C. Reducing nighttime light exposure in the urban environment to benefit human health and society. Science 380, 1130–1135 (2023).

    Article  ADS  CAS  PubMed  Google Scholar 

  5. Campbell, I., Sharifpour, R. & Vandewalle, G. Light as a modulator of non-image-forming brain functions—positive and negative impacts of increasing light availability. Clocks Sleep. 5, 116–140 (2023). This work presents a review of non-image-forming vision and the effects of light, in the context of changing lighting environments.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Vandewalle, G., Maquet, P. & Dijk, D.-J. Light as a modulator of cognitive brain function. Trends Cogn. Sci. 13, 429–438 (2009).

    Article  PubMed  Google Scholar 

  7. Beier, C., Zhang, Z., Yurgel, M. & Hattar, S. Projections of ipRGCs and conventional RGCs to retinorecipient brain nuclei. J. Comp. Neurol. 529, 1863–1875 (2021).

    Article  PubMed  Google Scholar 

  8. Warthen, D. M. & Provencio, I. The role of intrinsically photosensitive retinal ganglion cells in nonimage-forming responses to light. Eye Brain 4, 43–48 (2012).

    PubMed  PubMed Central  Google Scholar 

  9. Fisk, A. S. et al. Light and cognition: roles for circadian rhythms, sleep, and arousal. Front. Neurol. 9, 56 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  10. Brainard, G. C. & Hanifin, J. P. Photons, clocks, and consciousness. J. Biol. Rhythm. 20, 314–325 (2005).

    Article  CAS  Google Scholar 

  11. Gaggioni, G., Maquet, P., Schmidt, C., Dijk, D. J. & Vandewalle, G. Neuroimaging, cognition, light and circadian rhythms. Front. Syst. Neurosci. 8, 126 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  12. LeGates, T. A., Fernandez, D. C. & Hattar, S. Light as a central modulator of circadian rhythms, sleep and affect. Nat. Rev. Neurosci. 15, 443–454 (2014). This review provides useful details about melanopsin and ipRGCs, non-image-forming visual functions and the direct and indirect pathways through which ipRGCs can influence circadian rhythmicity, mood and cognition.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Münch, M. & Bromundt, V. Light and chronobiology: implications for health and disease. Dialogues Clin. Neurosci. 14, 448–453 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Takahashi, J. S. & Zatz, M. Regulation of circadian rhythmicity. Science 217, 1104–1111 (1982).

    Article  ADS  CAS  PubMed  Google Scholar 

  15. Vitaterna, M. H., Takahashi, J. S. & Turek, F. W. Overview of circadian rhythms. Alcohol. Res. Health 25, 85–93 (2001). This work is an essential, expert introduction to circadian rhythms.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Westland, S., Pan, Q. & Lee, S. A review of the effects of colour and light on non-image function in humans. Coloration Technol. 133, 349–361 (2017).

    Article  CAS  Google Scholar 

  17. Zeitzer, J. M., Dijk, D. J., Kronauer, R., Brown, E. & Czeisler, C. Sensitivity of the human circadian pacemaker to nocturnal light: melatonin phase resetting and suppression. J. Physiol. 526(Pt 3), 695–702 (2000).

    Article  PubMed  Google Scholar 

  18. Chellappa, S. L., Gordijn, M. C. & Cajochen, C. Can light make us bright? Effects of light on cognition and sleep. Prog. Brain Res. 190, 119–133 (2011).

    Article  PubMed  Google Scholar 

  19. Siraji, M. A., Kalavally, V., Schaefer, A. & Haque, S. Effects of daytime electric light exposure on human alertness and higher cognitive functions: a systematic review. Front. Psychol. 12, 765750 (2021).

    Article  PubMed  Google Scholar 

  20. Barack, D. L. & Krakauer, J. W. Two views on the cognitive brain. Nat. Rev. Neurosci. 22, 359–371 (2021).

    Article  CAS  PubMed  Google Scholar 

  21. Neisser, U. Cognitive Psychology: Classic Edition (Psychology Press, 2014).

  22. Poldrack, R. A. et al. The cognitive atlas: toward a knowledge foundation for cognitive neuroscience. Front. Neuroinform 5, 17 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Cajochen, C. Alerting effects of light. Sleep. Med. Rev. 11, 453–464 (2007).

    Article  PubMed  Google Scholar 

  24. Meyer, N., Harvey, A. G., Lockley, S. W. & Dijk, D. J. Circadian rhythms and disorders of the timing of sleep. Lancet 400, 1061–1078 (2022).

    Article  PubMed  Google Scholar 

  25. Rüger, M., Gordijn, M. C. M., Beersma, D. G. M., Vries, B. D. & Daan, S. Time-of-day-dependent effects of bright light exposure on human psychophysiology: comparison of daytime and nighttime exposure. Am. J. Physiol. Regul. Integr. Comp. Physiol. 290, R1413–R1420 (2006).

    Article  PubMed  Google Scholar 

  26. Cajochen, C. et al. High sensitivity of human melatonin, alertness, thermoregulation, and heart rate to short wavelength light. J. Clin. Endocrinol. Metab. 90, 1311–1316 (2005).

    Article  CAS  PubMed  Google Scholar 

  27. Chellappa, S. L. et al. Non-visual effects of light on melatonin, alertness and cognitive performance: can blue-enriched light keep us alert? PLoS ONE 6, e16429 (2011).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  28. Schöllhorn, I. et al. Melanopic irradiance defines the impact of evening display light on sleep latency, melatonin and alertness. Commun. Biol. 6, 228 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  29. Lok, R., Smolders, K., Beersma, D. G. M. & de Kort, Y. A. W. Light, alertness, and alerting effects of white light: a literature overview. J. Biol. Rhythm. 33, 589–601 (2018).

    Article  Google Scholar 

  30. Provencio, I. et al. A novel human opsin in the inner retina. J. Neurosci. 20, 600–605 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Qiu, X. et al. Induction of photosensitivity by heterologous expression of melanopsin. Nature 433, 745–749 (2005).

    Article  ADS  CAS  PubMed  Google Scholar 

  32. Vandewalle, G. et al. Daytime light exposure dynamically enhances brain responses. Curr. Biol. 16, 1616–1621 (2006).

    Article  CAS  PubMed  Google Scholar 

  33. Badia, P., Myers, B., Boecker, M., Culpepper, J. & Harsh, J. R. Bright light effects on body temperature, alertness, EEG and behavior. Physiol. Behav. 50, 583–588 (1991).

    Article  CAS  PubMed  Google Scholar 

  34. Souman, J. L., Tinga, A. M., Te Pas, S. F., van Ee, R. & Vlaskamp, B. N. S. Acute alerting effects of light: a systematic literature review. Behav. Brain Res. 337, 228–239 (2018).

    Article  PubMed  Google Scholar 

  35. Lockley, S. W. et al. Short-wavelength sensitivity for the direct effects of light on alertness, vigilance, and the waking electroencephalogram in humans. Sleep 29, 161–168 (2006).

    PubMed  Google Scholar 

  36. Sahin, L. & Figueiro, M. G. Alerting effects of short-wavelength (blue) and long-wavelength (red) lights in the afternoon. Physiol. Behav. 116–117, 1–7 (2013).

    Article  PubMed  Google Scholar 

  37. Phipps-Nelson, J., Redman, J. R., Dijk, D.-J. & Rajaratnam, S. M. W. Daytime exposure to bright light, as compared to dim light, decreases sleepiness and improves psychomotor vigilance performance. Sleep 26, 695–700 (2003).

    Article  PubMed  Google Scholar 

  38. Lok, R., Woelders, T., Gordijn, M. C. M., Hut, R. A. & Beersma, D. G. M. White light during daytime does not improve alertness in well-rested individuals. J. Biol. Rhythm. 33, 637–648 (2018). This study neatly illustrates the importance of considering the internal state of study participants, and other factors that may influence cognition.

    Article  Google Scholar 

  39. Katsuki, F. & Constantinidis, C. Bottom-up and top-down attention: different processes and overlapping neural systems. Neuroscientist 20, 509–521 (2014).

    Article  PubMed  Google Scholar 

  40. Min, B.-K., Jung, Y.-C., Kim, E. & Park, J. Y. Bright illumination reduces parietal EEG α activity during a sustained attention task. Brain Res. 1538, 83–92 (2013).

    Article  CAS  PubMed  Google Scholar 

  41. Killgore, W. D. S. et al. Blue light exposure enhances neural efficiency of the task positive network during a cognitive interference task. Neurosci. Lett. 735, 135242 (2020).

    Article  CAS  PubMed  Google Scholar 

  42. Vandewalle, G. et al. Brain responses to violet, blue, and green monochromatic light exposures in humans: prominent role of blue light and the brainstem. PLoS ONE 2, e1247 (2007).

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  43. Aston-Jones, G., Chen, S., Zhu, Y. & Oshinsky, M. L. A neural circuit for circadian regulation of arousal. Nat. Neurosci. 4, 732–738 (2001).

    Article  CAS  PubMed  Google Scholar 

  44. Gnyawali, S., Feigl, B., Adhikari, P. & Zele, A. J. The role of melanopsin photoreception on visual attention linked pupil responses. Eur. J. Neurosci. 55, 1986–2002 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Alexandre, C. et al. Decreased alertness due to sleep loss increases pain sensitivity in mice. Nat. Med. 23, 768–774 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Åkerstedt, T., Hallvig, D. & Kecklund, G. Normative data on the diurnal pattern of the Karolinska Sleepiness Scale ratings and its relation to age, sex, work, stress, sleep quality and sickness absence/illness in a large sample of daytime workers. J. Sleep. Res. 26, 559–566 (2017).

    Article  PubMed  Google Scholar 

  47. Vandewalle, G. et al. Effects of light on cognitive brain responses depend on circadian phase and sleep homeostasis. J. Biol. Rhythm. 26, 249–259 (2011).

    Article  Google Scholar 

  48. Diamond, A. Executive functions. Annu. Rev. Psychol. 64, 135–168 (2013). This work is an essential introduction to executive functions.

    Article  PubMed  Google Scholar 

  49. Miller, E. K. & Cohen, J. D. An integrative theory of prefrontal cortex function. Annu. Rev. Neurosci. 24, 167–202 (2001).

    Article  CAS  PubMed  Google Scholar 

  50. Morellini, F. Spatial memory tasks in rodents: what do they model? Cell Tissue Res. 354, 273–286 (2013).

    Article  PubMed  Google Scholar 

  51. Manoochehri, M. Up to the magical number seven: an evolutionary perspective on the capacity of short term memory. Heliyon 7, e06955 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  52. Lee, H.-H., Tu, Y.-C. & Yeh, S.-L. In search of blue-light effects on cognitive control. Sci. Rep. 11, 15505 (2021).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  53. Ferlazzo, F. et al. Effects of new light sources on task switching and mental rotation performance. J. Environ. Psychol. 39, 92–100 (2014).

    Article  Google Scholar 

  54. Hartstein, L. E., LeBourgeois, M. K. & Berthier, N. E. Light correlated color temperature and task switching performance in preschool-age children: preliminary insights. PLoS ONE 13, e0202973 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  55. Daneault, V. et al. Plasticity in the sensitivity to light in aging: decreased non-visual impact of light on cognitive brain activity in older individuals but no impact of lens replacement. Front. Physiol. 9, 1557 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  56. Vandewalle, G. et al. Blue light stimulates cognitive brain activity in visually blind individuals. J. Cogn. Neurosci. 25, 2072–2085 (2013). This work is one of a series of studies using sub-behaviourally impactful light stimuli to induce changes in measures of brain activity in the absence of behavioural changes, unique in the use of visually blind participants with ostensibly intact ipRGCs.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Vandewalle, G. et al. Wavelength-dependent modulation of brain responses to a working memory task by daytime light exposure. Cereb. Cortex 17, 2788–2795 (2007).

    Article  CAS  PubMed  Google Scholar 

  58. Alkozei, A. et al. Exposure to blue light increases subsequent functional activation of the prefrontal cortex during performance of a working memory task. Sleep 39, 1671–1680 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  59. Kandel, E. R., Dudai, Y. & Mayford, M. R. The molecular and systems biology of memory. Cell 157, 163–186 (2014). This work is an essential introduction to memory.

    Article  CAS  PubMed  Google Scholar 

  60. Kukushkin, N. V. & Carew, T. J. Memory takes time. Neuron 95, 259–279 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Korte, M. & Schmitz, D. Cellular and system biology of memory: timing, molecules, and beyond. Physiological Rev. 96, 647–693 (2016).

    Article  CAS  Google Scholar 

  62. Hartsock, M. J. & Spencer, R. L. Memory and the circadian system: identifying candidate mechanisms by which local clocks in the brain may regulate synaptic plasticity. Neurosci. Biobehav. Rev. 118, 134–162 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  63. Frankland, P. W., Josselyn, S. A. & Köhler, S. The neurobiological foundation of memory retrieval. Nat. Neurosci. 22, 1576–1585 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Clopath, C. Synaptic consolidation: an approach to long-term learning. Cogn. Neurodyn 6, 251–257 (2012).

    Article  PubMed  Google Scholar 

  65. Goto, A. Synaptic plasticity during systems memory consolidation. Neurosci. Res. 183, 1–6 (2022).

    Article  PubMed  Google Scholar 

  66. Alkozei, A., Smith, R., Dailey, N. S., Bajaj, S. & Killgore, W. D. S. Acute exposure to blue wavelength light during memory consolidation improves verbal memory performance. PLoS ONE 12, e0184884 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  67. Cajochen, C. et al. Evening exposure to a light-emitting diodes (LED)-backlit computer screen affects circadian physiology and cognitive performance. J. Appl. Physiol. 110, 1432–1438 (2011).

    Article  PubMed  Google Scholar 

  68. Ober, B. A. in Encyclopedia of the Neurological Sciences 2nd edn (eds Aminoff, M. J. & Daroff, R. B.) 1042–1044 (Academic, 2014).

  69. Jung, H.-C., Kim, J.-H. & Lee, C.-W. The effect of the illuminance of light emitting diode (LED) lamps on long-term memory. Displays 49, 1–5 (2017).

    Article  Google Scholar 

  70. Lee, C. W. & Kim, J. H. The influence of LED lighting on attention and long-term memory. Int. J. Opt. 2020, 8652108 (2020).

    Article  Google Scholar 

  71. Adolphs, R. Cognitive neuroscience of human social behaviour. Nat. Rev. Neurosci. 4, 165–178 (2003). This work is an essential introduction to social and emotional cognition.

    Article  CAS  PubMed  Google Scholar 

  72. Padilla-Coreano, N., Tye, K. M. & Zelikowsky, M. Dynamic influences on the neural encoding of social valence. Nat. Rev. Neurosci. 23, 535–550 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Vandewalle, G. et al. Spectral quality of light modulates emotional brain responses in humans. Proc. Natl Acad. Sci. USA 107, 19549–19554 (2010).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  74. Sabbah, S., Worden, M. S., Laniado, D. D., Berson, D. M. & Sanes, J. N. Luxotonic signals in human prefrontal cortex as a possible substrate for effects of light on mood and cognition. Proc. Natl Acad. Sci. USA 119, e2118192119 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Mure, L. S., Vinberg, F., Hanneken, A. & Panda, S. Functional diversity of human intrinsically photosensitive retinal ganglion cells. Science 366, 1251–1255 (2019).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  76. Schmidt, T. M. & Kofuji, P. Functional and morphological differences among intrinsically photosensitive retinal ganglion cells. J. Neurosci. 29, 476–482 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Wong, K. Y. A retinal ganglion cell that can signal irradiance continuously for 10 hours. J. Neurosci. 32, 11478–11485 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Bijleveld, E. & Knufinke, M. Exposure to bright light biases effort-based decisions. Behav. Neurosci. 132, 183–193 (2018).

    Article  PubMed  Google Scholar 

  79. Cawley, E. I. et al. Dopamine and light: dissecting effects on mood and motivational states in women with subsyndromal seasonal affective disorder. J. Psychiatry Neurosci. 38, 388–397 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  80. Kombeiz, O. & Steidle, A. Facilitation of creative performance by using blue and red accent lighting in work and learning areas. Ergonomics 61, 456–463 (2018).

    Article  PubMed  Google Scholar 

  81. Summers, T. A. & Hebert, P. R. Shedding some light on store atmospherics: influence of illumination on consumer behavior. J. Bus. Res. 54, 145–150 (2001).

    Article  Google Scholar 

  82. Guido, G., Piper, L., Prete, M. I., Mileti, A. & Trisolini, C. M. Effects of blue lighting in ambient and mobile settings on the intention to buy hedonic and utilitarian products. Psychol. Mark. 34, 215–226 (2017).

    Article  Google Scholar 

  83. Huiberts, L. M., Smolders, K. C. H. J. & de Kort, Y. A. W. Shining light on memory: effects of bright light on working memory performance. Behav. Brain Res. 294, 234–245 (2015).

    Article  CAS  PubMed  Google Scholar 

  84. Smolders, K. C. H. J. & de Kort, Y. A. W. Bright light and mental fatigue: effects on alertness, vitality, performance and physiological arousal. J. Environ. Psychol. 39, 77–91 (2014).

    Article  Google Scholar 

  85. Hattar, S. et al. Melanopsin and rod–cone photoreceptive systems account for all major accessory visual functions in mice. Nature 424, 76–81 (2003).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  86. Sonoda, T., Lee, S. K., Birnbaumer, L. & Schmidt, T. M. Melanopsin phototransduction is repurposed by iprgc subtypes to shape the function of distinct visual circuits. Neuron 99, 754–767.e4 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Zhao, X., Stafford, B. K., Godin, A. L., King, W. M. & Wong, K. Y. Photoresponse diversity among the five types of intrinsically photosensitive retinal ganglion cells. J. Physiol. 592, 1619–1636 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Schmidt, T. M. & Kofuji, P. Differential cone pathway influence on intrinsically photosensitive retinal ganglion cell subtypes. J. Neurosci. 30, 16262–16271 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Güler, A. D. et al. Melanopsin cells are the principal conduits for rod–cone input to non-image-forming vision. Nature 453, 102–105 (2008).

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  90. Fu, Y. et al. Intrinsically photosensitive retinal ganglion cells detect light with a vitamin A-based photopigment, melanopsin. Proc. Natl Acad. Sci. USA 102, 10339–10344 (2005).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  91. Fernandez, D. C. et al. Light affects mood and learning through distinct retina–brain pathways. Cell 175, 71–84.e18 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Hattar, S. et al. Central projections of melanopsin-expressing retinal ganglion cells in the mouse. J. Comp. Neurol. 497, 326–349 (2006). This work is an early description of ipRGC projections, essential for hypotheses regarding ipRGC inputs to cognitive systems.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Hattar, S., Liao, H. W., Takao, M., Berson, D. M. & Yau, K. W. Melanopsin-containing retinal ganglion cells: architecture, projections, and intrinsic photosensitivity. Science 295, 1065–1070 (2002).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  94. Aranda, M. L. & Schmidt, T. M. Diversity of intrinsically photosensitive retinal ganglion cells: circuits and functions. Cell Mol. Life Sci. 78, 889–907 (2021). This work is an essential introduction to ipRGCs, and the tools available to interrogate ipRGC circuits and related behaviours.

    Article  CAS  PubMed  Google Scholar 

  95. Bowrey, H. E., James, M. H., Omrani, M., Mohammadkhani, A. & Aston-Jones, G. Chemogenetic stimulation a retinal circuit activates brain noradrenergic neurons, prevents apoptosis suppresses depression-like behaviors. Preprint at bioRxiv https://doi.org/10.1101/2021.04.20.440684 (2021).

    Article  Google Scholar 

  96. LeGates, T. A. et al. Aberrant light directly impairs mood and learning through melanopsin-expressing neurons. Nature 491, 594–598 (2012).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  97. Nayak, S. K., Jegla, T. & Panda, S. Role of a novel photopigment, melanopsin, in behavioral adaptation to light. Cell Mol. Life Sci. 64, 144–154 (2007).

    Article  CAS  PubMed  Google Scholar 

  98. Zhang, Z., Beier, C., Weil, T. & Hattar, S. The retinal ipRGC–preoptic circuit mediates the acute effect of light on sleep. Nat. Commun. 12, 5115 (2021).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  99. Li, J. Y. & Schmidt, T. M. Divergent projection patterns of M1 ipRGC subtypes. J. Comp. Neurol. 526, 2010–2018 (2018). The findings of this study describe distinct populations of M1 ipRGCs, candidates in many non-image-forming behaviours.

    Article  PubMed  PubMed Central  Google Scholar 

  100. Do, M. T. H. Melanopsin and the intrinsically photosensitive retinal ganglion cells: biophysics to behavior. Neuron 104, 205–226 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Sondereker, K. B., Stabio, M. E. & Renna, J. M. Crosstalk: the diversity of melanopsin ganglion cell types has begun to challenge the canonical divide between image-forming and non-image-forming vision. J. Comp. Neurol. 528, 2044–2067 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Bliss, T. V. & Lomo, T. Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J. Physiol. 232, 331–356 (1973).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Basu, J. & Siegelbaum, S. A. The corticohippocampal circuit, synaptic plasticity, and memory. Cold Spring Harb. Perspect. Biol. 7, a021733 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  104. Warthen, D. M., Wiltgen, B. J. & Provencio, I. Light enhances learned fear. Proc. Natl Acad. Sci. USA 108, 13788–13793 (2011).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  105. Shan, L. L. et al. Light exposure before learning improves memory consolidation at night. Sci. Rep. 5, 15578 (2015).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  106. Lueptow, L. M. Novel object recognition test for the investigation of learning and memory in mice. J. Vis. Exp. 55718 https://doi.org/10.3791/55718 (2017).

  107. Tam, S. K. et al. Modulation of recognition memory performance by light requires both melanopsin and classical photoreceptors. Proc. Biol. Sci. 283, 20162275 (2016).

    PubMed  PubMed Central  Google Scholar 

  108. Hasan, S. et al. Modulation of recognition memory performance by light and its relationship with cortical EEG θ and γ activities. Biochem. Pharmacol. 191, 114404 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Gevins, A., Smith, M. E., McEvoy, L. & Yu, D. High-resolution EEG mapping of cortical activation related to working memory: effects of task difficulty, type of processing, and practice. Cereb. Cortex 7, 374–385 (1997).

    Article  CAS  PubMed  Google Scholar 

  110. Pitkänen, A., Pikkarainen, M., Nurminen, N. & Ylinen, A. Reciprocal connections between the amygdala and the hippocampal formation, perirhinal cortex, and postrhinal cortex in rat. A review. Ann. N. Y. Acad. Sci. 911, 369–391 (2000).

    Article  ADS  PubMed  Google Scholar 

  111. Curtis, C. E. & D’Esposito, M. Persistent activity in the prefrontal cortex during working memory. Trends Cogn. Sci. 7, 415–423 (2003).

    Article  PubMed  Google Scholar 

  112. Battaglia, F. P., Benchenane, K., Sirota, A., Pennartz, C. M. & Wiener, S. I. The hippocampus: hub of brain network communication for memory. Trends Cogn. Sci. 15, 310–318 (2011).

    PubMed  Google Scholar 

  113. Roesler, R., Parent, M. B., LaLumiere, R. T. & McIntyre, C. K. Amygdala–hippocampal interactions in synaptic plasticity and memory formation. Neurobiol. Learn. Mem. 184, 107490 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  114. Horner, A. J. & Doeller, C. F. Plasticity of hippocampal memories in humans. Curr. Opin. Neurobiol. 43, 102–109 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Scoville, W. B. & Milner, B. Loss of recent memory after bilateral hippocampal lesions. J. Neurol. Neurosurg. Psychiatry 20, 11–21 (1957).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Lisman, J. et al. Viewpoints: how the hippocampus contributes to memory, navigation and cognition. Nat. Neurosci. 20, 1434–1447 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Knierim, J. J., Neunuebel, J. P. & Deshmukh, S. S. Functional correlates of the lateral and medial entorhinal cortex: objects, path integration and local–global reference frames. Philos. Trans. R. Soc. Lond. B Biol. Sci. 369, 20130369 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  118. Baddeley, A. Working memory. Science 255, 556–559 (1992). This work is an essential introduction to working memory.

    Article  ADS  CAS  PubMed  Google Scholar 

  119. Stuss, D. T. & Benson, D. F. Neuropsychological studies of the frontal lobes. Psychol. Bull. 95, 3 (1984).

    Article  CAS  PubMed  Google Scholar 

  120. Florin-Lechner, S. M., Druhan, J. P., Aston-Jones, G. & Valentino, R. J. Enhanced norepinephrine release in prefrontal cortex with burst stimulation of the locus coeruleus. Brain Res. 742, 89–97 (1996).

    Article  CAS  PubMed  Google Scholar 

  121. Roecklein, K. et al. The post illumination pupil response is reduced in seasonal affective disorder. Psychiatry Res. 210, 150–158 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  122. Heatherton, T. F. et al. Medial prefrontal activity differentiates self from close others. Soc. Cogn. Affect. Neurosci. 1, 18–25 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  123. Hu, R. K. et al. An amygdala-to-hypothalamus circuit for social reward. Nat. Neurosci. 24, 831–842 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Dwortz, M. F., Curley, J. P., Tye, K. M. & Padilla-Coreano, N. Neural systems that facilitate the representation of social rank. Philos. Trans. R. Soc. Lond. B Biol. Sci. 377, 20200444 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  125. Jobson, D. D., Hase, Y., Clarkson, A. N. & Kalaria, R. N. The role of the medial prefrontal cortex in cognition, ageing and dementia. Brain Commun. 3, fcab125 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  126. Saalmann, Y. B. & Kastner, S. Cognitive and perceptual functions of the visual thalamus. Neuron 71, 209–223 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. O’Connor, D. H., Fukui, M. M., Pinsk, M. A. & Kastner, S. Attention modulates responses in the human lateral geniculate nucleus. Nat. Neurosci. 5, 1203–1209 (2002).

    Article  PubMed  Google Scholar 

  128. Baker, P. M. et al. The lateral habenula circuitry: reward processing and cognitive control. J. Neurosci. 36, 11482–11488 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Hermans, E. J. et al. How the amygdala affects emotional memory by altering brain network properties. Neurobiol. Learn. Mem. 112, 2–16 (2014).

    Article  PubMed  Google Scholar 

  130. McIntyre, C. K., McGaugh, J. L. & Williams, C. L. Interacting brain systems modulate memory consolidation. Neurosci. Biobehav. Rev. 36, 1750–1762 (2012).

    Article  PubMed  Google Scholar 

  131. Roozendaal, B., Hahn, E. L., Nathan, S. V., Dominique, J.-F. & McGaugh, J. L. Glucocorticoid effects on memory retrieval require concurrent noradrenergic activity in the hippocampus and basolateral amygdala. J. Neurosci. 24, 8161–8169 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Roozendaal, B., McReynolds, J. R. & McGaugh, J. L. The basolateral amygdala interacts with the medial prefrontal cortex in regulating glucocorticoid effects on working memory impairment. J. Neurosci. 24, 1385–1392 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. McIntyre, C. K. et al. Memory-influencing intra-basolateral amygdala drug infusions modulate expression of Arc protein in the hippocampus. Proc. Natl Acad. Sci. USA 102, 10718–10723 (2005).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  134. Roozendaal, B., Castello, N. A., Vedana, G., Barsegyan, A. & McGaugh, J. L. Noradrenergic activation of the basolateral amygdala modulates consolidation of object recognition memory. Neurobiol. Learn. Mem. 90, 576–579 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Wang, G. et al. Short-term acute bright light exposure induces a prolonged anxiogenic effect in mice via a retinal ipRGC–CeA circuit. Sci. Adv. 9, eadf4651 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Raam, T. & Hong, W. Organization of neural circuits underlying social behavior: a consideration of the medial amygdala. Curr. Opin. Neurobiol. 68, 124–136 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Zhang, W.-H., Zhang, J.-Y., Holmes, A. & Pan, B.-X. Amygdala circuit substrates for stress adaptation and adversity. Biol. Psychiatry 89, 847–856 (2021).

    Article  PubMed  Google Scholar 

  138. Jiao, X., Beck, K., Myers, C., Servatius, R. & Pang, K. Altered activity of the medial prefrontal cortex and amygdala during acquisition and extinction of an active avoidance task. Front. Behav. Neurosci. 9, 249 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  139. McCue, M. G., LeDoux, J. E. & Cain, C. K. Medial amygdala lesions selectively block aversive Pavlovian–instrumental transfer in rats. Front. Behav. Neurosci. 8, 329 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  140. Cartoni, E., Puglisi-Allegra, S. & Baldassarre, G. The three principles of action: a Pavlovian–instrumental transfer hypothesis. Front. Behav. Neurosci. 7, 153 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  141. Berry, M. H. et al. A melanopsin ganglion cell subtype forms a dorsal retinal mosaic projecting to the supraoptic nucleus. Nat. Commun. 14, 1492 (2023).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  142. Hu, J. et al. Melanopsin retinal ganglion cells mediate light-promoted brain development. Cell 185, 3124–3137.e15 (2022).

    Article  CAS  PubMed  Google Scholar 

  143. Liao, P. Y., Chiu, Y. M., Yu, J. H. & Chen, S. K. Mapping central projection of oxytocin neurons in unmated mice using Cre and alkaline phosphatase reporter. Front. Neuroanat. 14, 559402 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Huang, Y.-F., Liao, P.-Y., Yu, J.-H. & Chen, S.-K. Light disrupts social memory via a retina-to-supraoptic nucleus circuit. EMBO Rep. 24, e56839 (2023). This work presents a recent finding demonstrating direct effects of light on cognition, mediated by ipRGCs, using several of the techniques discussed.

    Article  CAS  PubMed  Google Scholar 

  145. Deurveilher, S. & Semba, K. Indirect projections from the suprachiasmatic nucleus to major arousal-promoting cell groups in rat: implications for the circadian control of behavioural state. Neuroscience 130, 165–183 (2005).

    Article  CAS  PubMed  Google Scholar 

  146. Breton-Provencher, V., Drummond, G. T. & Sur, M. Locus coeruleus norepinephrine in learned behavior: anatomical modularity and spatiotemporal integration in targets. Front. Neural Circuits 15, 638007 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Aston-Jones, G., Rajkowski, J. & Cohen, J. Role of locus coeruleus in attention and behavioral flexibility. Biol. Psychiatry 46, 1309–1320 (1999).

    Article  CAS  PubMed  Google Scholar 

  148. Maness, E. B. et al. Role of the locus coeruleus and basal forebrain in arousal and attention. Brain Res. Bull. 188, 47–58 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Aston-Jones, G., Rajkowski, J. & Cohen, J. In Progress in Brain Research 126 (eds. Uyliǹgs H. B. M. et al.) 165–182 (Elsevier, 2000).

  150. Záborszky, L. et al. Specific basal forebrain–cortical cholinergic circuits coordinate cognitive operations. J. Neurosci. 38, 9446–9458 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  151. Peirson, S. N., Brown, L. A., Pothecary, C. A., Benson, L. A. & Fisk, A. S. Light and the laboratory mouse. J. Neurosci. Methods 300, 26–36 (2018). This work presents a wealth of practical information for laboratory mouse husbandry and experimental design (including a list of melatonin-deficient and sufficient lines) that takes the effects of light and ipRGC photoreception into account.

    Article  PubMed  PubMed Central  Google Scholar 

  152. Chellappa, S. L. et al. Photic memory for executive brain responses. Proc. Natl Acad. Sci. USA 111, 6087–6091 (2014).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  153. Spitschan, M. & Woelders, T. The method of silent substitution for examining melanopsin contributions to pupil control. Front. Neurol. 9, 941 (2018). This work includes detailed and accessible explanations of the fundamental concepts behind silent substitution, including an essential discussion of the overlapping spectral sensitivities of photoreceptors.

    Article  PubMed  PubMed Central  Google Scholar 

  154. Rushton, W. A. H. Review lecture. Pigments and signals in colour vision. J. Physiol. 220, 1–31 (1972).

    Article  Google Scholar 

  155. McDowell, R. J. et al. Beyond lux: methods for species and photoreceptor-specific quantification of ambient light for mammals. Preprint at bioRxiv https://doi.org/10.1101/2023.08.25.554794 (2023). This preprint establishes resources for the most current α-opic light measurement and reporting across species.

  156. Hannibal, J. et al. Melanopsin is expressed in PACAP-containing retinal ganglion cells of the human retinohypothalamic tract. Invest. Ophthalmol. Vis. Sci. 45, 4202–4209 (2004).

    Article  PubMed  Google Scholar 

  157. Mure, L. S. Intrinsically photosensitive retinal ganglion cells of the human retina. Front. Neurol. 12, 636330 (2021). This ipRGC review focuses specifically on the state of knowledge of human ipRGCs.

    Article  PubMed  PubMed Central  Google Scholar 

  158. Göz, D. et al. Targeted destruction of photosensitive retinal ganglion cells with a saporin conjugate alters the effects of light on mouse circadian rhythms. PLoS ONE 3, e3153 (2008).

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  159. An, K. et al. A circadian rhythm-gated subcortical pathway for nighttime-light-induced depressive-like behaviors in mice. Nat. Neurosci. 23, 869–880 (2020).

    Article  CAS  PubMed  Google Scholar 

  160. Huang, L. et al. A visual circuit related to habenula underlies the antidepressive effects of light therapy. Neuron 102, 128–142.e8 (2019).

    Article  CAS  PubMed  Google Scholar 

  161. Gao, F. et al. A non-canonical retina–ipRGCs–SCN–PVT visual pathway for mediating contagious itch behavior. Cell Rep. 41, 111444 (2022).

    Article  MathSciNet  CAS  PubMed  PubMed Central  Google Scholar 

  162. Kennaway, D. J., Voultsios, A., Varcoe, T. J. & Moyer, R. W. Melatonin in mice: rhythms, response to light, adrenergic stimulation, and metabolism. Am. J. Physiol. Regul. Integr. Comp. Physiol. 282, R358–R365 (2002).

    Article  CAS  PubMed  Google Scholar 

  163. Altimus, C. M. et al. Rods–cones and melanopsin detect light and dark to modulate sleep independent of image formation. Proc. Natl Acad. Sci. USA 105, 19998–20003 (2008).

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  164. Grillon, C., Pellowski, M., Merikangas, K. R. & Davis, M. Darkness facilitates the acoustic startle reflex in humans. Biol. Psychiatry 42, 453–460 (1997).

    Article  CAS  PubMed  Google Scholar 

  165. Thompson, S., Lupi, D., Hankins, M. W., Peirson, S. N. & Foster, R. G. The effects of rod and cone loss on the photic regulation of locomotor activity and heart rate. Eur. J. Neurosci. 28, 724–729 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  166. Ishida, A. et al. Light activates the adrenal gland: timing of gene expression and glucocorticoid release. Cell Metab. 2, 297–307 (2005).

    Article  CAS  PubMed  Google Scholar 

  167. Pilorz, V. et al. Melanopsin regulates both sleep-promoting and arousal-promoting responses to light. PLoS Biol. 14, e1002482 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  168. Huang, Y., Zhou, W. & Zhang, Y. Bright lighting conditions during testing increase thigmotaxis and impair water maze performance in BALB/c mice. Behav. Brain Res. 226, 26–31 (2012).

    Article  PubMed  Google Scholar 

  169. Milosavljevic, N., Cehajic-Kapetanovic, J., Procyk, C. A. & Lucas, R. J. Chemogenetic activation of melanopsin retinal ganglion cells induces signatures of arousal and/or anxiety in mice. Curr. Biol. 26, 2358–2363 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Lucas, R. J. et al. Measuring and using light in the melanopsin age. Trends Neurosci. 37, 1–9 (2014).

    Article  CAS  PubMed  Google Scholar 

  171. Enezi, J. A. et al. A “melanopic” spectral efficiency function predicts the sensitivity of melanopsin photoreceptors to polychromatic lights. J. Biol. Rhythm. 26, 314–323 (2011).

    Article  Google Scholar 

  172. Lucas, R. J. et al. In the eye of the beholder: measuring and standardising light for laboratory mammals. Preprint at https://www.preprints.org/manuscript/202309.1766/v1 (2023). This preprint provides the most current expert consensus on using, measuring and reporting light used with laboratory mammals, including a discussion of colour vision across species.

  173. Vanuk, J. R. et al. Morning blue light treatment improves sleep complaints, symptom severity, and retention of fear extinction memory in post-traumatic stress disorder. Front. Behav. Neurosci. 16, 886816 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Chen, P., Ban, W., Wang, W., You, Y. & Yang, Z. The devastating effects of sleep deprivation on memory: lessons from rodent models. Clocks Sleep. 5, 276–294 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  175. Smies, C. W., Bodinayake, K. K. & Kwapis, J. L. Time to learn: the role of the molecular circadian clock in learning and memory. Neurobiol. Learn. Mem. 193, 107651 (2022). This work presents a current discussion of circadian rhythms and memory.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Xu, S., Akioma, M. & Yuan, Z. Relationship between circadian rhythm and brain cognitive functions. Front. Optoelectron. 14, 278–287 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  177. Diekelmann, S. & Born, J. The memory function of sleep. Nat. Rev. Neurosci. 11, 114–126 (2010).

    Article  CAS  PubMed  Google Scholar 

  178. Gerstner, J. R. & Yin, J. C. Circadian rhythms and memory formation. Nat. Rev. Neurosci. 11, 577–588 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  179. Vartanian, G. V. et al. Melatonin suppression by light in humans is more sensitive than previously reported. J. Biol. Rhythm. 30, 351–354 (2015).

    Article  CAS  Google Scholar 

  180. Bedrosian, T. A. & Nelson, R. J. Timing of light exposure affects mood and brain circuits. Transl. Psychiatry 7, e1017 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Krishnan, H. C. & Lyons, L. C. Synchrony and desynchrony in circadian clocks: impacts on learning and memory. Learn. Mem. 22, 426–437 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Domagalik, A. et al. Long-term reduction of short-wavelength light affects sustained attention and visuospatial working memory with no evidence for a change in circadian rhythmicity. Front. Neurosci. 14, 654 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  183. Riemersma-van der Lek, R. F. et al. Effect of bright light and melatonin on cognitive and noncognitive function in elderly residents of group care facilities: a randomized controlled trial. JAMA 299, 2642–2655 (2008).

    Article  CAS  PubMed  Google Scholar 

  184. Yamadera, H. et al. Effects of bright light on cognitive and sleep–wake (circadian) rhythm disturbances in Alzheimer-type dementia. Psychiatry Clin. Neurosci. 54, 352–353 (2000).

    Article  CAS  PubMed  Google Scholar 

  185. Huang, X. et al. A visual circuit related to the nucleus reuniens for the spatial-memory-promoting effects of light treatment. Neuron 109, 347–362.e7 (2021).

    Article  CAS  PubMed  Google Scholar 

  186. Milosavljevic, N., Brown, T. M. & Lucas, R. J. A bright idea for improving spatial memory. Neuron 109, 197–199 (2021).

    Article  CAS  PubMed  Google Scholar 

  187. Miller, H. V., Barnes, J. C. & Beaver, K. M. Self-control and health outcomes in a nationally representative sample. Am. J. Health Behav. 35, 15–27 (2011).

    Article  PubMed  Google Scholar 

  188. La Morgia, C. et al. Multimodal investigation of melanopsin retinal ganglion cells in Alzheimer’s disease. Ann. Clin. Transl. Neurol. 10, 918–932 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  189. La Morgia, C. et al. Melanopsin retinal ganglion cell loss in Alzheimer disease. Ann. Neurol. 79, 90–109 (2016).

    Article  PubMed  Google Scholar 

  190. Oh, A. J. et al. Pupillometry evaluation of melanopsin retinal ganglion cell function and sleep–wake activity in pre-symptomatic Alzheimer’s disease. PLoS ONE 14, e0226197 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  191. Myers, B. L. & Badia, P. Changes in circadian rhythms and sleep quality with aging: mechanisms and interventions. Neurosci. Biobehav. Rev. 19, 553–571 (1995).

    Article  CAS  PubMed  Google Scholar 

  192. Murman, D. L. The impact of age on cognition. Semin. Hear. 36, 111–121 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  193. Vugler, A. A., Joseph, A. & Jeffery, G. Survival and remodeling of melanopsin cells during retinal dystrophy. Vis. Neurosci. 25, 125–138 (2008).

    Article  PubMed  Google Scholar 

  194. Cui, Q., Ren, C., Sollars, P., Pickard, G. & So, K.-F. The injury resistant ability of melanopsin-expressing intrinsically photosensitive retinal ganglion cells. Neuroscience 284, 845–853 (2015).

    Article  CAS  PubMed  Google Scholar 

  195. Turner, P. L. & Mainster, M. A. Circadian photoreception: ageing and the eye’s important role in systemic health. Br. J. Ophthalmol. 92, 1439–1444 (2008).

    Article  CAS  PubMed  Google Scholar 

  196. Esquiva, G., Lax, P., Pérez-Santonja, J. J., García-Fernández, J. M. & Cuenca, N. Loss of melanopsin-expressing ganglion cell subtypes and dendritic degeneration in the aging human retina. Front. Aging Neurosci. 9, 79 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  197. Cajochen, C., Münch, M., Knoblauch, V., Blatter, K. & Wirz-Justice, A. Age-related changes in the circadian and homeostatic regulation of human sleep. Chronobiol. Int. 23, 461–474 (2006).

    Article  PubMed  Google Scholar 

  198. Beier, C. et al. Divergent outer retinal circuits drive image and non-image visual behaviors. Cell Rep. 39, 111003 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  199. Maruani, J. & Geoffroy, P. A. Multi-level processes and retina–brain pathways of photic regulation of mood. J. Clin. Med. 11, 448 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  200. Rupp, A. C. et al. Distinct ipRGC subpopulations mediate light’s acute and circadian effects on body temperature and sleep. eLife 8, e44358 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  201. Gooley, J. J., Lu, J., Fischer, D. & Saper, C. B. A broad role for melanopsin in nonvisual photoreception. J. Neurosci. 23, 7093–7106 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Desgranges, B., Baron, J. C. & Eustache, F. The functional neuroanatomy of episodic memory: the role of the frontal lobes, the hippocampal formation, and other areas. Neuroimage 8, 198–213 (1998).

    Article  CAS  PubMed  Google Scholar 

  203. Nakajima, M. & Schmitt, L. I. Understanding the circuit basis of cognitive functions using mouse models. Neurosci. Res. 152, 44–58 (2020). This work presents an indispensable in-depth discussion of techniques available to dissect cognitive functions in mouse models, including behavioural tasks, circuit dissection and neural recording techniques.

    Article  PubMed  Google Scholar 

  204. Arakawa, H. & Iguchi, Y. Ethological and multi-behavioral analysis of learning and memory performance in laboratory rodent models. Neurosci. Res. 135, 1–12 (2018).

    Article  PubMed  Google Scholar 

  205. Ghafarimoghadam, M. et al. A review of behavioral methods for the evaluation of cognitive performance in animal models: current techniques and links to human cognition. Physiol. Behav. 244, 113652 (2022).

    Article  CAS  PubMed  Google Scholar 

  206. Isik, S. & Unal, G. Open-source software for automated rodent behavioral analysis. Front. Neurosci. 17, 1149027 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  207. Guenthner, C. J., Miyamichi, K., Yang, H. H., Heller, H. C. & Luo, L. Permanent genetic access to transiently active neurons via TRAP: targeted recombination in active populations. Neuron 78, 773–784 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  208. Patel, A. A., McAlinden, N., Mathieson, K. & Sakata, S. Simultaneous electrophysiology and fiber photometry in freely behaving mice. Front. Neurosci. 14, 148 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  209. Bush, G., Shin, L. M., Holmes, J., Rosen, B. R. & Vogt, B. A. The multi-source interference task: validation study with fMRI in individual subjects. Mol. Psychiatry 8, 60–70 (2003).

    Article  CAS  PubMed  Google Scholar 

  210. Einhäuser, W. in Computational and Cognitive Neuroscience of Vision (ed. Zhao, Q.) 141–169 (Springer, 2017).

  211. Owen, A. M., McMillan, K. M., Laird, A. R. & Bullmore, E. n-Back working memory paradigm: a meta-analysis of normative functional neuroimaging studies. Hum. Brain Mapp. 25, 46–59 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  212. Yi, A. in Encyclopedia of Clinical Neuropsychology (eds Kreutzer, J. S., DeLuca, J. & Caplan, B.) 475–476 (Springer, 2011).

  213. Karayanidis, F. & McKewen, M. in Psychology of Learning and Motivation Vol. 74 (ed. Federmeier, K. D.) 141–193 (Academic, 2021).

  214. Emmer, K. M., Russart, K. L. G., Walker, W. H., Nelson, R. J. & DeVries, A. C. Effects of light at night on laboratory animals and research outcomes. Behav. Neurosci. 132, 302–314 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  215. Hofstetter, J. R., Hofstetter, A. R., Hughes, A. M. & Mayeda, A. R. Intermittent long-wavelength red light increases the period of daily locomotor activity in mice. J. Circadian Rhythm. 3, 8 (2005).

    Article  Google Scholar 

  216. Roedel, A., Storch, C., Holsboer, F. & Ohl, F. Effects of light or dark phase testing on behavioural and cognitive performance in DBA mice. Lab. Anim. 40, 371–381 (2006).

    Article  CAS  PubMed  Google Scholar 

  217. Dauchy, R. T. & Blask, D. E. Vivarium lighting as an important extrinsic factor influencing animal-based research. J. Am. Assoc. Lab. Anim. Sci. 62, 3–25 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  218. Chellappa, S. L., Steiner, R., Oelhafen, P. & Cajochen, C. Sex differences in light sensitivity impact on brightness perception, vigilant attention and sleep in humans. Sci. Rep. 7, 14215 (2017).

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  219. Levine, D. A. et al. Sex differences in cognitive decline among US adults. JAMA Netw. Open. 4, e210169 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  220. Yagi, S. & Galea, L. A. M. Sex differences in hippocampal cognition and neurogenesis. Neuropsychopharmacology 44, 200–213 (2019).

    Article  PubMed  Google Scholar 

  221. Cowan, R. et al. Sex differences in response to red and blue light in human primary visual cortex: a bold fMRI study. Psychiatry Res. 100, 129–138 (2001).

    Article  ADS  Google Scholar 

  222. Krizo, J. A. & Mintz, E. M. Sex differences in behavioral circadian rhythms in laboratory rodents. Front. Endocrinol. 5, 234 (2014).

    Google Scholar 

Download references

Acknowledgements

The authors are grateful to J. Bhoi for edits improving the clarity and content of the manuscript with valuable suggestions and insight on neuromodulation.

Author information

Authors and Affiliations

  1. Department of Neurobiology, Northwestern University, Evanston, IL, USA

    Heather L. Mahoney & Tiffany M. Schmidt

Authors
  1. Heather L. Mahoney
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tiffany M. Schmidt
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The authors contributed equally to all aspects of the article.

Corresponding authors

Correspondence to Heather L. Mahoney or Tiffany M. Schmidt.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Neuroscience thanks Christian Cajochen and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Glossary

Circadian rhythms

Natural rhythms that oscillate over a period of approximately 24 h.

Cognitive inhibition

(Also known as inhibitory control). An element of executive function that refers to the ability to control behaviour, thoughts and emotions, and to apply selective attention while tuning out irrelevant stimuli.

Cognitive neurobehavioural performance

A subject’s ability to complete cognitive tasks, which may be relatively improved or diminished by various stimuli and states.

Declarative memory

Memory of facts and events, sometimes referred to as explicit memory.

Electroencephalography

(EEG). A technique used to measure brain activity, in which electrical fields are detected at the scalp surface.

Emotional cognition

(Closely tied to social cognition). The ability to recognize and understand the feelings of others and the self.

Functional connectivity

Neurons within a circuit that synaptically communicate.

Functional magnetic resonance imaging

(fMRI). A brain imaging method that maps brain metabolism, or blood oxygen level-dependent (BOLD) signals.

Light therapy

(Also called phototherapy). The use of artificial or natural light as a treatment, most commonly for seasonal depression.

Melanopsin

A light-sensitive opsin protein (encoded by the gene OPN4) that is expressed in intrinsically photosensitive retinal ganglion cells (ipRGCs).

Melatonin

A sleep-promoting hormone that is synthesized in and released by the pineal gland. Melatonin levels both follow and have a role in synchronizing circadian rhythms.

Neuromodulatory systems

Systems (including the cholinergic, dopaminergic, noradrenergic and serotonergic systems) that regulate other systems by using neurotransmitters to signal throughout the brain.

Non-declarative memory

(Also referred to as procedural or implicit memory). Memory for skills, habits, procedures and other types of non-associative conditioning.

Photoreceptors

Light-sensitive cells that, in mammals, are found in the retina.

Principle of univariance

A principle stating that activation of an opsin molecule by a single photon of any wavelength will result in an identical cellular response.

Recognition memory

The ability to recognize and recall previously encountered stimuli.

Reward processing

The engagement of neurobiological pathways enabling the experience of reward, association with rewarding stimuli and subsequent shaping of behaviour.

Theory of mind

The ability to infer or attribute mental states, such as desires, intentions and thoughts, of the self and others.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mahoney, H.L., Schmidt, T.M. The cognitive impact of light: illuminating ipRGC circuit mechanisms. Nat. Rev. Neurosci. 25, 159–175 (2024). https://doi.org/10.1038/s41583-023-00788-5

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41583-023-00788-5

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing