Cells In The Retina Suppress Brain Activity To Modulate Circadian Rhythms

A section of a mouse retina. Cell nuclei are blue, RNA for the GABA inhibitory molecule is labeled in magenta, and ipRCGs are labeled in green. Northwestern University

Light falling on our retinas triggers signals that pass up the optic nerve, causing neurons to fire in the brain so we can process what we see. Long after scientists discovered this fact they have learned its not the whole story; some of the retina's cells do the opposite, suppressing activity in the brain. It will probably be a long time before we really grasp the reasons for this, but it appears to make for a more stable circadian rhythm and therefore sleeping cycles.

Biologists call messages that increase neuron firing 'excitatory signaling' and those that reduce activity 'inhibitory signaling'. It has been taken for granted for decades that the eye only produces excitatory signals.

Dr Takuma Sonada has overthrown that idea with a paper in Science, based on his work while a PhD student at Northwestern University reporting on a subset of retinal ganglial cells (RCGs) whose signals are inhibitory.

Sonanda and team leader Dr Tiffany Schmidt blocked the inhibitory retinal neurons in mice and found their circadian rhythms became more affected by low light.

“These inhibitory signals prevent our circadian clock from resetting to dim light and prevent pupil constriction in low light, both of which are adaptive for proper vision and daily function,” Schmidt said in a statement

Image from a mouse retinal section where cell nuclei are labeled in blue, RNA for the GABA synthesis enzyme Gad2 is labeled in magenta, and RNA for melanopsin is labeled in green.

“This suggests that there is a signal from the eye that actively inhibits circadian rhythms' realignment when environmental light changes, which was unexpected,” Schmidt said. “This makes some sense, however, because you do not want to adjust your body’s entire clock for minor perturbations in the environmental light/dark cycle, you only want this massive adjustment to take place if the change in lighting is robust."

For our ancestors, this might have prevented the body's master clock been thrown off by a full Moon or a campfire. Considering the lights we are now exposed to, it may be an even more useful feature in the modern world.

The inhibitory signals also appeared to stop mouse pupils from constricting too much when exposed to low light, enabling them to see in the near-dark.

Most RCGs are activated by the rod and cone photoreceptors that act as the eye's main way of capturing light, but those Sonada and Schmidt studied are intrinsically photosensitive RGCs (ipRCGs). These can be activated by light even without rods or cones. In an accompanying commentary piece on the discovery, student Jennifer Ding and Dr Wei Wei of the University of Chicago note mice have at least six different ipRCGs. Little is known about these, leaving open the possibility even more unexpected features may be revealed with further study.

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