November 26, 2019
The transitions that mark the beginning and end of human life are marked by the same phenomenon: light. In fact, a new study conducted at the University of California-Berkeley has found that, eve by the second trimester—long before a baby’s eyes can see images—they can detect light.
Previously, the light-sensitive cells in the developing retina— the thin sheet of brain-like tissue at the back of the eye— were assumed to be simple” on-off switches,” presumably there to set up the 24-hour, day-night rhythms parents hope their baby will follow.
Now, with funding from the National Institutes of Health, researchers have discovered evidence that these simple cells actually talk to one another as part of an interconnected network that gives the retina more light sensitivity than once thought, and that may enhance the influence of light on behavior and brain development in unsuspected ways.
In mice and monkeys, recent evidence suggests that these ganglion cells also talk with one another through electrical connections called gap junctions, implying much more complexity in immature rodent and primate eyes than imagined.
“Given the variety of these ganglion cells and that they project to many different parts of the brain, it makes me wonder whether they play a role in how the retina connects up to the brain,” said Marla Feller, a UC Berkeley professor of molecular and cell biology and senior author of a paper that appeared this month in the journal Current Biology. “Maybe not for visual circuits, but for non-vision behaviors. Not only the pupillary light reflex and circadian rhythms, but possibly explaining problems like light-induced migraines, or why light therapy works for depression.”
The cells, called intrinsically photosensitive retinal ganglion cells (ipRGCs), were discovered only ten years ago, surprising those such as Feller, who had been studying the developing retina for nearly 20 years. She played a major role, along with her mentor, Carla Shatz of Stanford University, in showing that spontaneous electrical activity in the eye during development— so-called retinal waves —is critical for setting up the correct brain networks to process images later on.
UC Berkeley graduate student Franklin Caval-Holme combined two-photon calcium imaging, whole-cell electrical recording, pharmacology, and anatomical techniques to show that the six types of ipRGCs in the newborn mouse retina link up electrically, via gap junctions, to form a retinal network that the researchers found not only detects light, but responds to the intensity of the light, which can vary nearly a billionfold.
Gap junction circuits were critical for light sensitivity in some ipRGC subtypes, but not others, providing a potential avenue to determine which ipRGC subtypes provide the signal for specific non-visual behaviors that light evokes.
“Aversion to light, which pups develop very early, is intensity-dependent,” suggesting that these neural circuits could be involved in light-aversion behavior, Caval-Holme said. “We don’t know which of these ipRGC subtypes in the neonatal retina actually contributes to the behavior, so it will be very interesting to see what role all these different subtypes have.”
The researchers also found evidence that the circuit tunes itself in a way that could adapt to the intensity of light, which probably has an important role in development, Feller said.
Research contact: @EurekaAlert