Neural Circuits: Avoiding UV light

The larvae of an annelid worm use nitric oxide signalling to activate the neural pathways needed to swim away from the harmful ultraviolet light of the sun.
  1. Maria Sachkova
  2. Vengamanaidu Modepalli  Is a corresponding author
  1. School of Biological Sciences, University of Bristol, United Kingdom
  2. Marine Biological Association of the UK, United Kingdom

Living deep within our oceans, lakes, and ponds are small animals known as zooplankton which typically rise to the surface of the water at night and sink towards the bottom during the day. This synchronised movement helps zooplankton avoid harmful ultraviolet (UV) light and escape diurnal predators that hunt during the day (Malloy et al., 1997).

Most marine invertebrates progress through a ciliated larval stage during their life cycle, and this larva will swim freely like zooplankton before settling on the seafloor and transforming into an adult. During this free-swimming stage, the ciliated larvae also avoid UV light, making them a useful model for studying how zooplankton behave. In the larvae of the annelid worm Platynereis dumerilii, this response is controlled by ciliary photoreceptor cells which detect UV wavelengths via a light-sensitive protein known as c-opsin1 (Verasztó et al., 2018; Conzelmann et al., 2013; Arendt et al., 2004). The larvae of other marine invertebrates also use this mechanism to sense UV light (Jékely et al., 2008). However, it was unclear how this sensory input is relayed to the parts of the nervous system that trigger the larvae to swim downwards away from the sun. Now, in eLife, Gáspár Jékely and colleagues – including Kei Jokura as first author – report that P. dumerilii larvae use the gaseous signalling molecule nitric oxide to pass on this information (Jokura et al., 2023).

The team (who are based at the University of Exeter, University of Bristol, Okinawa Institute of Science and Technology and University of Heidelberg) found that the enzyme responsible for generating nitric oxide, nitric oxide synthase (or NOS for short), is expressed in interneurons that reside in the apical organ region, the part of the larva that receives sensory input. Previously collected electron microscopy data from the whole larval body of P. dumerilii was then analysed (Williams et al., 2017), which revealed that these NOS-expressing interneurons lay immediately downstream of UV-sensing ciliary photoreceptor cells.

To further test whether nitric oxide is involved in UV avoidance, Jokura et al. studied P. dumerilii larvae that had been genetically modified so that any nitric oxide produced by these animals emits a fluorescent signal. They found that UV exposure led to higher levels of fluorescence in the part of the larva where the NOS-expressing interneurons project their dendrites and axons. Furthermore, mutant larvae lacking the gene for NOS did not respond as well to UV light, an effect that has been observed previously in mutant larvae that do not have properly working c-opsin1 photoreceptors (Verasztó et al., 2018). These findings confirm the role of nitric oxide in UV-avoidance.

Next, Jokura et al. investigated how nitric oxide signalling affects the activity of ciliary photoreceptor cells using a fluorescent sensor that can detect changes in calcium levels: the more calcium is present, the more active the cell. UV light exposure caused the ciliary photoreceptors to experience two increases in calcium. This biphasic response depended on c-opsin1 and nitric oxide molecules being retrogradely sent from the NOS-expressing interneurons back to the ciliary photoreceptor cells.

Jokura et al. also identified two unconventional nitrate sensing guanylate cyclases (called NIT-GC1 and NIT-GC2) which mediate nitric oxide signalling in the ciliary photoreceptor cells. These proteins are located in different regions of the photoreceptor and may therefore be involved in different intracellular signalling pathways. Experiments with mutant larvae lacking NIT-GC1 confirmed that this protein is necessary for retrograde nitric oxide signalling to ciliary photoreceptor cells. This leads to a delayed and sustained activation of the ciliary photoreceptors, which then drives the circuit during the second increase in calcium. A mathematical model that analysed the dynamics of the neural circuit, and individual cells within it, confirmed that the magnitude of the nitric oxide signal depends on the intensity and duration of the UV stimulus.

In conclusion, Jokura et al. propose that when P. dumerilii larvae are exposed to UV light, this activates ciliary photoreceptors, which, in turn, triggers postsynaptic interneurons to produce nitric oxide (Figure 1). The nitric oxide signal is then sent back to the ciliary photoreceptors, causing them to sustain their activity (even once the stimulus is gone) via an unconventional guanylate cyclase. This late activation inhibits neurons which promote cilia movement. Jokura et al. propose that slowing the beat of certain cilia may rotate the larva so that its head is pointing downwards, causing it to swim away from UV light at the water surface.

The neural circuit that instructs ciliated larvae to avoid UV light.

Two- and three-day-old larvae of the annelid Platynereis dumerilii swim downwards to avoid UV exposure from the sun. The UV light is detected by ciliary photoreceptor cells (cPRCs, pink) which activate interneurons (INNOS, blue) downstream by increasing their calcium (Ca2+) levels. This triggers the enzyme nitrogen oxygen synthase (NOS) to generate the gaseous signalling molecule nitric oxide (NO) which is sent back to the ciliary photoreceptors. Nitric oxide interacts with a nitrate sensing guanylate cyclase (NIT-GC1) which sustains the activity of the ciliary photoreceptors. This signal activates a chain of downstream neurons resulting in the larvae swimming downwards away from UV light at the water surface.

As animals have evolved, their light-response systems have become increasingly sophisticated, especially with the addition of neurons which have further refined this process. Nitric oxide is an ancient signalling molecule that regulates many processes in animals, and its newly discovered role in the ciliated larvae of P. dumerilii may help researchers find missing connections in the light-sensing pathways of other marine invertebrates.

References

Article and author information

Author details

  1. Maria Sachkova

    Maria Sachkova is in the School of Biological Sciences, University of Bristol, Bristol, United Kingdom

    Competing interests
    No competing interests declared
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4721-0510
  2. Vengamanaidu Modepalli

    Vengamanaidu Modepalli is at the Marine Biological Association of the UK, Plymouth, United Kingdom

    For correspondence
    vengamanaidumodepalli@gmail.com
    Competing interests
    No competing interests declared
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3099-4969

Publication history

  1. Version of Record published: October 18, 2023 (version 1)

Copyright

© 2023, Sachkova and Modepalli

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 472
    Page views
  • 47
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Maria Sachkova
  2. Vengamanaidu Modepalli
(2023)
Neural Circuits: Avoiding UV light
eLife 12:e92535.
https://doi.org/10.7554/eLife.92535

Further reading

    1. Neuroscience
    2. Stem Cells and Regenerative Medicine
    Junjun Yao, Shaoxing Dai ... Tianqing Li
    Research Article

    While accumulated publications support the existence of neurogenesis in the adult human hippocampus, the homeostasis and developmental potentials of neural stem cells (NSCs) under different contexts remain unclear. Based on our generated single-nucleus atlas of the human hippocampus across neonatal, adult, aging, and injury, we dissected the molecular heterogeneity and transcriptional dynamics of human hippocampal NSCs under different contexts. We further identified new specific neurogenic lineage markers that overcome the lack of specificity found in some well-known markers. Based on developmental trajectory and molecular signatures, we found that a subset of NSCs exhibit quiescent properties after birth, and most NSCs become deep quiescence during aging. Furthermore, certain deep quiescent NSCs are reactivated following stroke injury. Together, our findings provide valuable insights into the development, aging, and reactivation of the human hippocampal NSCs, and help to explain why adult hippocampal neurogenesis is infrequently observed in humans.

    1. Developmental Biology
    2. Neuroscience
    Kristine B Walhovd, Stine K Krogsrud ... Didac Vidal-Pineiro
    Research Article

    Human fetal development has been associated with brain health at later stages. It is unknown whether growth in utero, as indexed by birth weight (BW), relates consistently to lifespan brain characteristics and changes, and to what extent these influences are of a genetic or environmental nature. Here we show remarkably stable and lifelong positive associations between BW and cortical surface area and volume across and within developmental, aging and lifespan longitudinal samples (N = 5794, 4–82 y of age, w/386 monozygotic twins, followed for up to 8.3 y w/12,088 brain MRIs). In contrast, no consistent effect of BW on brain changes was observed. Partly environmental effects were indicated by analysis of twin BW discordance. In conclusion, the influence of prenatal growth on cortical topography is stable and reliable through the lifespan. This early-life factor appears to influence the brain by association of brain reserve, rather than brain maintenance. Thus, fetal influences appear omnipresent in the spacetime of the human brain throughout the human lifespan. Optimizing fetal growth may increase brain reserve for life, also in aging.