#SFN2018 (Theme F) Shining Bright Despite the Plight - Light affects mood through a retina-brain direct connection

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#1

Light and Mood: From retina to brain


Although we don’t photosynthesize our food, animals including humans are as reliant as plants on the nurturing light emanating from our sun rhythmically for hours each day. This light sets our circadian rhythm and times all of the important physiological functions that rise and fall over the course of the day. But light has other powerful effects on our minds, and when light availability is disrupted either naturally or by our busy lifestyles, our moods and cognitive function suffer greatly.

In order for our brain to receive this vitally important light, it must pass first through the photoreceptor cells in our retinas. Most of us are familiar with these ‘rods’ and ‘cones,’ which perceive dim, black and white light or rich colors and motion, respectively. But there is another type of photorecipient cell, called the intrinsically photosensitive Retinal Ganglion Cell, (ipRGC) which express the light sensitive protein melanopsin and transmits light information directly to the brain enclosed in its dark skull. These cells directly synapse onto the suprachiasmatic nucleus, the master circadian pacemaker in mammals, and research into their role has largely been limited to the clock.

Previously, Samer Hattar’s lab has shown that ablation of these cells fully disables the circadian clock’s ability to entrain to light cues. But in addition to this loss of internal timekeeping, light’s affect on mood and learning was also lost. Diego Fernandez took this to mean the ipRGC’s were responsible for mediating this effect, and at his talk on Day 1 of SFN, explained his delineation of two Retina-Brain pathways which enable light to modulate both learning and mood in mice.


(Fernandez et. al. Cell, 2018)
While the talk was excellent, the paper is even better, and I highly recommend giving it a read to fully appreciate their beautiful experiment construction and all of the supporting information. I recognize this post must sell their work short, but here are the quick points highlighted in Diego’s talk

  • Mice kept in a disturbed light cycle called T7 (3.5 hours of light then 3.5 hours of dark) perform worse on assays of memory and learning, such as the Novel Object test and Morris Water Maze. This light-based effect on learning and memory requires the ipRGC - to - SCN connected cells.

  • The T7 light cycle also causes mood deficits in mice, as measured by sucrose preference and Forced Swim tests. However, this deficit is lost when the ipRGC - to - SCN cells are genetically and specifically ablated.

So if not the SCN, then where does light have its mood-affective impact? They traced ipRGC projections to the perihabenular nucleus, and showed that this poorly described region was both strongly light-activated, and projected to other mood-related areas, such as the vmPFC. In short, the non-SCN directed ipRGC’s were connected to mood areas by only two synapses, and this thalamic relay circuit is responsible for light’s direct affect on mood regulation, at least in mice.

It will be very interesting to see if these findings shape the direction of neuropsychiatric treatments in the future. We all suffer more now than ever before from a preponderance of light at night, and maybe that’s having a non-negligible effect on dramatically rising depression rates in the US, and across the developed world. Disclaimer: this is only my speculation and hand-waving, but I’m very curious to see how this bears out into the future.


Benjamin Bell
PhD Candidate, Johns Hopkins School of Medicine
Sleep and Circadian Rhythms, Mark Wu Lab