Photoreceptor cells in mice drive visual and non-visual functions using separate circuits in the eye

The According to a new mouse study from the National Eye Institute (NEI) and the National Institute of Mental Health (NIMH). The 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 if and how non-image-forming visual behaviors depend on these same pathways in the eye,” Johan said. Pahlberg, Ph.D., head of NEI’s Photoreceptor Physiology Group and senior study author.

Vision begins when light enters the eye and strikes the light-sensitive photoreceptors in the retina. Photoreceptors transfer signals through several layers of retinal neurons before those signals are sent to the brain. Light also triggers certain non-visual functions, such as controlling the amount of light that enters the eye through the pupil (pupillary light reflex) and regulating the sleep/wake cycle (circadian rhythm). Circadian rhythm disruption has been linked to sleep problems, obesity, and other health problems.

To study the pathways used by image-forming functions versus 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 their next neuronal downstream. neighbors, called bipolar cells. The group investigated the roles of rod photoreceptors, which are sensitive to low levels of light; conical photoreceptors, which see color; as well as three types of bipolar cells: rod bipolar cells, cone “on” bipolar cells, and cone “off” bipolar cells.

Cone “on” bipolar cells respond to increases in light, and cone “off” bipolar cells respond to decreases in light. Cone photoreceptors can only communicate with cone bipolar cells, while rod photoreceptors have pathways to communicate with each of the bipolar cell types, depending on the level of light. The bipolar cells then communicate with other neurons in the retina, passing information to the optic nerve and the brain. Some mice in the study lacked functional connections between rods and “on” bipolar cells, for example, or connections between cones and bipolar cells, or lacked connections between rod and cone photoreceptors. .

The researchers compared the mice’s responses to visual stimuli while assessing pupillary light responses and monitoring their nocturnal sleep/wake cycle. They determined that while image-forming vision can use rod and cone photoreceptors, as well as all types of bipolar cells, the same cannot be said for non-image-forming functions. The pupil response relies exclusively on the rod photoreceptors, while the cones are unable to control this behavior. Meanwhile, circadian rhythm regulation and pupillary reflex only use “on” bipolar cell pathways, relying on rod bipolar cells and cone “on” bipolar cells, but not bipolar cells with “off” cone.

“We were really surprised to find that animals with only ‘turned off’ bipolar cells cannot adapt to changes in the day/night cycle, but can still see and react to visual events, which means they have a functional view of image formation. It was really interesting to us that the non-imaging training functions completely ignore information of the ‘out’ way,” Pahlberg said. “We were also surprised that rod photoreceptors, optimized for low light conditions, were still used for pupillary response even when light levels were high. We really thought the rods would be maxed out at this time.

Pahlberg expects many of these findings in mice to hold for humans, because the retinal circuitry is similar in mammals. In the future, he intends to explore other non-image forming functions of the retina, such as mood regulation, and see how these different retinal circuits are used in other ways.

The research was funded by the intramural programs of the NEI, NIMH, National Institute of Dental and Craniofacial Research, and National Institute of Neurological Diseases and Stroke.

This press release describes a basic research result. Basic research improves our understanding of human behavior and biology, which is fundamental to advancing new and better ways to prevent, diagnose and treat disease. Science is an unpredictable and incremental process – each advance in research builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research. To learn more about basic research, visit https://www.nih.gov/news-events/basic-research-digital-media-kit.

NEI leads federal government research on the visual system and eye disease. NEI supports basic and clinical science programs to develop sight-saving treatments and address the special needs of people with vision loss. For more informationvisit https://www.nei.nih.gov.

About the National Institutes of Health (NIH): The NIH, the country’s medical research agency, comprises 27 institutes and centers and is part of the US Department of Health and Human Services. The NIH is the primary federal agency that conducts and supports basic, clinical, and translational medical research, and studies the causes, treatments, and cures for common and rare diseases. For more information about the NIH and its programs, visit www.nih.gov.

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