ON or OFF

Though it is well known that some photosensitive retinal ganglion cells drive non-image forming vision, there is much we don’t know. New research undertaken by the Photoreceptor Physiology group of the National Institute of Health aimed to unlock additional insight into the behaviors of the retinal circuits driving the process. Here, Johan Pahlberg, Senior Scientist and leader of the research group at the National Eye Institute breaks down the main findings.

Could you first provide some context to your research?
 

Besides the classical photoreceptors in the retina – the rods (which my lab is particularly interested in) and the cones – there are also intrinsically photosensitive retinal ganglion cells that are known to control non-image forming vision, including circadian photoentrainment, the pupillary light response (PLR), mood, and sleep. How they connect to different brain regions is increasingly becoming understood thanks to the efforts and research of many labs – most notably the Hattar Lab, with whom we collaborated on this project.

The outer retinal circuits that drive image-forming vision (that is consciously perceived) have been extensively studied and clearly defined, but the behaviors of the circuits that drive the retinal ganglion cells involved in non-image forming vision remain entirely unknown. With help from our colleagues, we were able to obtain several different mouse lines in which we were able to manipulate different rod and cone retinal pathways, and study how they might influence these behaviors.

What’s your elevator pitch for the study?
 

We observed that the retinal circuits driving image and non-image forming visual behaviors are distinct and mostly non-overlapping (1). Perhaps the most interesting feature of our visual system is the fact that both increases and decreases in light are detected in what are known as the ON and OFF pathways. Remarkably, the ON pathway is dispensable for image-forming vision; the OFF pathway can convey sufficient information to compensate for its absence. In stark contrast to image-forming vision, we found that the OFF pathway does not play any role in non-image forming visual behaviors.

This surprising revelation raises several interesting questions about the evolution of vision and the ON and OFF pathways in the retina, when and how different retinal cell types evolved, and how they connect in the retinal circuitry, and why non-image forming vision completely disregards a major parallel information stream to the brain (the OFF pathway).

Our work could be viewed as a starting blueprint for how to comprehensively dissect neuronal circuits and their function – and thus how to possibly understand deficits in vision.

What are the next steps for your research – and your expectations for the future?
 

We used a simple vision behavior test (did the mice see or not see a flash of light) and two non-image forming behaviors – the PLR and circadian photoentrainment, so there are several other different behaviors we can use to assess if the retinal circuits are similar or different. Our mouse lines also open up the possibility to comprehensively study and understand how the different rod retinal pathways operate in the retina.