NIH researchers decode retinal circuitry for circadian rhythm, pupillary light response
The eye’s light-sensing retina taps different circuits depending on whether it produces image-forming vision or performs non-visual functions such as regulating pupil size or the sleep/wake cycle, according to a new mouse study from the National Eye Institute. NEI) and the National Institute of Mental Health (NIMH). These findings could have implications for understanding how our eyes help regulate mood, digestion, sleep and metabolism. NEI and NIMH are part of the National Institutes of Health.
“We know a lot about the pathways involved in image-forming vision, but until now it was unknown whether and how non-image-forming visual behavior depended on these same pathways in the eye,” says Johan Pahlberg, Ph.D., head of Photoreceptor Physiology Group at NEI and senior author of the study.
Vision begins when light enters the eye and hits the light-sensing photoreceptors of the retina. Photoreceptors transfer signals through several layers of retinal neurons before they are sent to the brain. Light also triggers certain non-visual functions, such as controlling how much light enters the eye through the pupil (pupillary light reflex) and regulating the wake/sleep cycle (circadian rhythm). Circadian rhythm disturbances have been linked to sleep problems, obesity, and other health problems.
To investigate the pathways used by image-forming versus non-image-forming functions in the retina, Pahlberg and colleagues studied groups of mice that had been genetically modified to turn off one or more pathway links, or synapses, between photoreceptors and subsequent downstream neurons. neighbors, called bipolar cells. The group investigated the role of rod photoreceptors, which are sensitive to low light levels; cone photoreceptors, which perceive color; and three types of bipolar cells: rod bipolar cells, “active” cone bipolar cells, and “inactive” cone bipolar cells.
“Active” cone bipolar cells react to an increase in light, and an “off” cone bipolar cell to react to a decrease in light. Cone photoreceptors can only communicate with cone bipolar cells, whereas rod photoreceptors have pathways for communicating with each type of bipolar cell, depending on light levels. The bipolar cells then communicate with other neurons in the retina, relaying information to the optic nerve and to the brain. Some of the mice in this study did not have a functional association between rods and bipolar cells, for example, or a relationship between cones and bipolar cells, or had no association between rods and cones photoreceptors.
The researchers compared the mice’s responses to visual stimuli while assessing pupillary light responses and monitoring their sleep/wake cycles. They determined that while image-forming vision can use rods and cones photoreceptors, as well as all types of bipolar cells, the same is not true for non-image-forming functions. Pupil response depends exclusively on rod photoreceptors, while cones cannot control this behavior. Meanwhile, both circadian rhythm regulation and pupillary reflexes use only “on” bipolar cell pathways, relying on “on” bipolar rods and cones, but not “off” bipolar cells.
“We were really surprised to find that animals with only ‘dead’ bipolar cells were unable to adjust to changes in the day/night cycle, but were still able to see and respond to visual events, meaning they had functional image-forming vision. It is of great interest to us that the non-imaging shaping function completely ignores information from the ‘off’ path,” said Pahlberg. “We were equally surprised that rod photoreceptors, optimized for low-light conditions, were still used for pupillary response even when light levels were high. We really think the stick will be maxed out at that point. ”
Pahlberg hopes many of these findings in mice will apply to humans, because retinal circuits are similar across mammals. Going forward, he intends to explore other non-image-forming functions of the retina, such as mood regulation, and see how else these different retinal circuits are used.
This research was funded by the NEI intramural program, NIMH, the National Institute of Dental and Craniofacial Research, and the National Institute of Neurological Disease and Stroke.
This press release describes the basic research findings. Basic research improves our understanding of human behavior and biology, which is the basis for advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and gradual process – any research progress builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without a basic knowledge of basic research. To learn more about basic research, visit https://www.nih.gov/news-events/basic-research-digital-media-kit.
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