There’s more to vision than meets the eye. Research has shown that the neurological processes that lead to vision are more involved than previously thought. Work at the Picower Institute for Learning and Memory at the Massachusetts Institute of Technology showed that neurons in the brain’s visual system add and shed synapses at a fast pace during vision development. Research at the Jules Stein Eye Institute at the David Geffen School of Medicine at UCLA found that cells in the retina can rewire themselves when vision deteriorates as a result of retinitis pigmentosa.
Building Binocular Vision
Scientists have known that the brain’s visual system isn’t hardwired from birth. The visual system becomes refined over time by what babies see. Researchers at the Picower Institute were surprised to learn about the amount of rewiring that takes place when they saw the process happening in mice in real-time.
Scientists tracked the vision of mice as they watched black and white gratings with lines of specific orientation and direct of movement drift across their field of view. At the same time, they observed both the structure and activity of the neuron’s soma, its main body, and of the spines along the neuron’s dendrites. They tracked the structure of 793 dendritic spines on 14 neurons day 1, day 5 and day 10 of the critical development period. By tracking the activity at the same time, the scientists could quantify the visual information the neurons received at each connection at the synapse. Lastly, by linking a spine’s structural change during the critical period to its activity, they hoped to discover the process by which the synaptic turnover honed binocular vision.
The scientists found that 32 percent of the spines evident on day 1 were gone by day 5, and 24 percent of the spines that were found on day 5 were added since day 1. The time between days 5 and 10 had similar turnover: 27 percent were eliminated and 24 percent were added. By day 10, only 40 percent of the spines seen on day 1 lasted that long. In addition, 4 of the 13 neurons they were tracking that responded to visual stimuli still responded by day 10.
What was it that allowed some spines to survive over the 10-day critical period? Earlier studies showed that the first inputs to reach the binocular visual cortex neurons are from the eye on the opposite side. In other words, the right eye’s inputs arrive to the left hemisphere first. The inputs drive the neuron’s soma to respond to a specific visual property, such as a straight or diagonal line. By the time the critical period starts, inputs from the eye on the same side of the head join the “race” to the visual cortex neurons. This allows them to become binocular.
Since researchers were tracking activity at the spines in real-time, they could see what triggered the activity and how often they were active. Over time, they learned that the spines were more likely to survive if they were more active and responded to the same orientation of the one the soma preferred. Interestingly, spines that responded to both eyes were more active than ones that just responded to one eye.
Another development that they noticed was that over the 10 days clusters emerged along the dendrites where neighboring spines were likely to be active at the same time. That means during the critical period neurons enhanced their role in binocular vision by selectively retaining inputs that reinforced their orientation preferences. They did so both by the volume of activity and their association with their neighbors.
Both of these mechanisms are essential during the critical period to propel the turnover of misaligned spines. This leads to the enhancement of binocular responses such as orientation that matches both eyes.
Rewiring Vision
What happens at the cellular level when vision fails as a result of a disease, such as retinitis pigmentosa? Scientists at the Jules Stein Eye Institute at the David Geffen School of Medicine at UCLA found that certain retinal cells can rewire themselves when vision deteriorates due to retinitis pigmentosa.
Retinitis pigmentosa is the leading cause of inherited blindness and it is a disease that progresses slowly. Yet, some patients are able to maintain usable vision into middle age. Researchers wanted to learn why that is and if it can be used as a treatment target.
The study used rhodopsin knockout mice that model early retinitis pigmentosa, where the rod bipolar cells don’t respond to light and degeneration happens slowly. Scientists recorded the electrical activity of the rod bipolar cells to see how they acted when their usual input was taken away. They also used other mouse models that lacked components of rod signaling to learn what activates the rewiring process.
What they found is that the rod bipolar cells’ neurons, which usually receive signals from rods that provide night vision, form new connections with cones that provide daytime vision when the rods stop working. These responses were strong and had the characteristics of cone-driven signals. The rewiring happened in mice with rod degeneration. It didn’t happen in other mouse models that didn’t have rod light responses without cell death. This implies that the rewiring is triggered by the degeneration process, not just the lack of light responses or broken synapses.
This work complements the researchers’ work in 2023 that showed cone cells can remain functional even in later disease stages when there were severe structural changes. Both these studies show that retinal circuits are functional through various adaptations at different stages of disease progression.
“Our findings show that the retina adapts to the loss of rods in ways that attempt to preserve daytime light sensitivity in the retina,” said senior study author A.P. Sampath, PhD of the UCLA Stein Eye Institute. “The signal for this plasticity appears to be degeneration itself, perhaps through the role of glial support cells or factors released by dying cells.”
The next question to consider is whether the rewiring is a general mechanism used by the retina when the rods die. Scientists are investigating this with other mice that carry the rhodopsin mutation and other rod proteins that cause retinitis pigmentosa.
Research projects like those at the Picower Institute and UCLA, show how that there is more to learn about vision. The work at Picower showed how involved the vision system’s development really is and how that contributes to what we see. The work at UCLA shows that even in a degenerative disease like retinitis pigmentosa, the rod cells don’t just lay down and die. They make connections with cone cells, which gives a patient functional vision. While scientists haven’t learned everything there is to learn about vision, their work is adding to the knowledge base and that in turn can lead to treatments for vision disease, where there once were none.
Sources:
https://picower.mit.edu/news/connect-or-reject-extensive-rewiring-builds-binocular-vision-brain
https://www.uclahealth.org/news/release/eye-cells-rewire-themselves-when-vision-begins-fail/a>