A new Yale School of Medicine (YSM) study has uncovered surprising new details about how our eyes process what we see.
When we look at something, our visual system breaks down different aspects of the scene – such as colour, contrast, and motion – and processes those components separately. It’s called parallel visual processing and it’s what allows our brains to work out what we’re seeing so quickly.
This separation of information starts in the retina, and scientists have thought that separation is maintained as the information travels through the visual system. But in a study published in Neuron, researchers have found that information channels are more integrated than previously thought. This may help cells process weak visual signals, such as low-light conditions, the researchers say.
“We found that while different channels can deliver their own features, they’re also interconnected by underlying electrical circuitry,” says Yao Xue, PhD, a postdoctoral fellow in the department of ophthalmology and visual science at YSM and the study’s first author.
Untangling bipolar cell signals in the retina
The rods and cones in our retinas detect light and transmit signals to a type of neuron called bipolar cells. In these cells, visual components such as night, day, colour, shape, and contrast begin to separate into more than a dozen parallel channels.
But when researchers zoomed in on bipolar cell synapses, they found these information channels intermingle.
Neurons have two types of synapses: chemical and electrical. At chemical synapses, neurons release chemical messengers known as neurotransmitters that bind to the recipient cell. Electrical synapses, also known as gap junctions, facilitate communication with electric currents. Bipolar cells primarily communicate through chemical synapses.
The researchers found, however, that in the mouse and human retinas they studied, electric synapses were integrating most of those seemingly separate bipolar cell information channels. When the scientists electrically stimulated one bipolar cell, instead of seeing a localised release of neurotransmitters just within that cell’s channel, they observed cloud-like patterns of signalling – suggesting crosstalk among the different types of cells.
“When we stimulated one bipolar cell, many bipolar cells released neurotransmitters,” says Z. Jimmy Zhou, PhD, Professor of Ophthalmology and Visual Science and principal investigator.
“If the signal is already very weak and is divided into several channels, there isn’t much left for each channel to process. The integration is particularly useful for detecting low contrast signals or signals from very small objects.”
Seunghoon Lee, PhD Research Scientist of Ophthalmology and Visual Science
To their surprise, they also identified one type of bipolar cell, called BC6, that drove this signalling. These cells generated strong signals that travelled through the parallel channels in a hierarchical manner. “People had assumed that the different types of bipolar cells were more or less autonomous,” Zhou says. “But we found a driver among all these cell types that creates this network with a hierarchy.”
Having distinct parallel channels can help bipolar cells divide and conquer as they process different parts of a visual signal. The linkage of these channels through electrical synapses, on the other hand, could help the cells process weak visual signals, the researchers say.
“If the signal is already very weak and is divided into several channels, there isn’t much left for each channel to process,” says Seunghoon Lee, PhD, a research scientist in the department of ophthalmology and visual Science at YSM and co-corresponding author of the study. “The integration is particularly useful for detecting low contrast signals or signals from very small objects.”
“And the cells aren’t cooperating in a random way,” adds Xue. “There’s a commander within them – BC6 – that leads them in relaying signals to the downstream target.”
Recording from hard-to-reach cells
For the study, the researchers used several methods to study the synaptic circuitry of bipolar cells, including imaging to observe the cells’ activity and how they released and responded to neurotransmitters, as well as stimulating activity in bipolar cells and recording responses in recipient cells.
One challenge of studying signal transmission in bipolar cells is that they live in the middle of the retina. Previous studies have cut the retina into slices in order to access the cells, but that can disrupt the synaptic circuitry. In the new study, however, the researchers were able to apply the dual patch-clamp technique in fully intact mouse retinas. This method uses electrodes to stimulate activity in different types of bipolar cells and records the responses of recipient cells.
“No other lab in the world has been able to pull off these kinds of recordings systematically,” says Zhou. “It is a tour de force of Yao Xue’s PhD thesis work, pairing an innovative approach with exceptional electrophysiological skill.”
The team then repeated the experiment in human retinas, which they obtained from the department of pathology’s Legacy Tissue Donation Program. These are the first experiments of their kind in an intact human retina, the YSM researchers say.
Source: Yale School of Medicine
