Harvard Medical School
Neurons use unexpected method to detect shifting amounts of light.

Light-sensing neurons use an unexpected system to detect changing amounts of environmental illumination, according to a new study by neuroscientists at Harvard Medical School and Boston Children’s Hospital.

The cells divvy up the job, with particular neurons tuned to different ranges of light intensity, the researchers reported in Cell on September 28.

“As the earth turns, the level of illumination ranges across many orders of magnitude, from starlight to full daylight. How do you build a sensory system that covers such a broad range?” asked the study’s senior author, Michael Do, assistant professor of neurology at Harvard Medical School and a research associate at the Fred Morgan Kirby Neurobiology Center at Boston Children’s. “It seems like a straightforward problem, but the solution we found was a lot more complex than expected.”

We rely on light-sensing neurons known as M1 ganglion cell photoreceptors to run our circadian clocks, regulate sleep and control hormone levels. Separate from the retina’s rods and cones, M1 cells specialize in “non-image” vision and function, even in people who are blind.

Doctor of Philosophy Elliott Milner student in Harvard’s Program in Neuroscience and the paper’s lead author, established new methods to study M1 cells’ electrical outputs. This allowed a better understanding of the signals these cells send from the eye to areas throughout the brain.

“The expectation from prior work was that signaling from these cells would simply increase with brightness, and that averaging across them would provide a measure of the overall light intensity,” said Milner.

Instead, Milner and Do found that while the cells look the same, they are tuned to respond to different light levels, and they take turns signaling the brain as these levels change. As a result, the brain gets information about light intensity from the identities of the cells that are active, not just signal size.

“Some cells signal vigorously in twilight and others in full daylight,” said Milner. “Together, they cover a broad range of light intensities in the environment.”

Leveraging a “pathological” phenomenon.

The M1 cells’ turn-taking system uses a mechanism that is usually considered abnormal or pathological: depolarization block.

As the light level goes up, a protein called melanopsin in the M1 cells captures more and more photons. This causes the voltage across the cell membrane to become more positive - that is, it depolarizes. As the voltage becomes more positive, the cell generates more electrical spikes, also known as action potentials, which are sent to the brain.

In depolarization block, typically observed in disorders such as epilepsy, the cell cannot fire spikes when the membrane voltage gets too positive.

“There’s so much excitation that the cell can’t keep up and it goes silent,” said Do.

The M1 cells seem to be using this feature to their advantage. Milner and Do think this system may have evolved to help the brain distinguish light levels more precisely, based on which cells are talking and not only their general volume. It also may conserve energy.

“Spikes are expensive metabolically for a cell to produce,” Do explained. “Because some cells are silenced as others activate, this system provides information at a lower energetic cost.”

The brain’s division of labor.

In future work, Milner and Do hope to explore the following questions.

How does the brain extract information about the light level from these cells? Do particular regions of the brain listen to some M1 cells and not others? How are the different M1 cells distributed across the retina? Different parts of the retina receive light from different directions, so how M1 cells are distributed could have implications for designing light therapy systems for conditions like seasonal affective disorder. Do other cells involved in sensory perception - such as those that allow us to sense odors or touch - also use depolarization block?

“The bottom line is that nerve cells have more in their toolkit than we previously thought, and divide labor in ways we didn’t expect,” said Do. “We’re finding surprises even in systems that are considered to be quite simple, like the one used to sense light intensity.”

The study was supported by the National Institutes of Health, the Whitehall Foundation and The Karl Kirchgessner Foundation.