Halfway There: A New Discovery and a New Direction

July 15th, 2015 by FFB Canada

Research doesn’t always go as planned. There are always surprises. This is because science deals with the unknown. While researchers do their best to gather information (sometimes referred to as preliminary data) to help design the optimal approach to a problem, there are usually unexpected outcomes. Although some of these surprises might be discouraging, others are tremendously exciting as they open the door to an entirely new way of seeing the world.

To get a better sense of what Foundation-funded researchers are thinking about midway through a three-year operating grant, we chatted with Dr. Gautam Awatramani at the University of Victoria, who has an exciting new discovery and also a new direction for the next phase of his project.

First – the new discovery

Before diving into the details, it helps to remember that our fight to end blindness focuses on three core research questions:

1) How can we save people’s remaining vision?

2) How can we restore sight to people who have lost their vision?

3) How does vision work?

In fact, learning more about how vision works helps researchers to find new ways to answer the first two questions. Before you can really fix something, it helps to understand what is broken. This is where Dr. Awatramani comes in. Thanks to his international team of collaborators, we are one step closer to understanding vision.  The team recently reported their important discovery about a key cell type in the eye: amacrine cells. These beautiful, star-shaped cells play an important role in transmitting contextual information about the environment (such as direction and size).

Amacrine cells are critically important for vision because they control the flow of visual information—Dr. Awatramani and his team set out to figure out how they do it. To learn more about how amacrine cells work, the team set up a series of clever experiments. As a starting point, the team knew that some amacrine cells were not active in dim light, so they looked more closely at what was happening under these conditions and discovered that one key function of amacrine cells – size detection – was hindered while their ability to detect the direction of moving objects was maintained. Next, the team looked at the eye cells that connect to amacrine cells: bipolar cells and ganglion cells. Bipolar cells connect to photoreceptors (the eyes light-sensing cells) and ganglion cells connect to the brain. By studying this inner network of cells (interneurons), the team discovered that two types of amacrine cells act in the middle to shape the contextual information about the environment (such as spatial and directional signals).

Alex Hoggarth, lead author of the study, told us why he is particularly excited about these results: Since we now know that there are two amacrine cells [dictating these functions], we guessed that they must be affected differently by the amount of light hitting the retina. This means that a single neural circuit can “re-wire” to use different interneurons in different situations to best suit the needs of the retina.  Alex agrees that before you can really fix something, it helps to understand what is broken, which is why he hopes that this new knowledge about how the eye makes important visual computations will aid in the development of retinal prosthetics or genetic vision regeneration strategies.

Second – the new direction

These key insights are also helping to inform the new direction that Dr. Awatramani is taking his research with the aim of restoring vision. He explains “we have taken a detour in attempting to define some the basic properties of retinal circuits, which we found to be surprisingly complex. With this knowledge in hand we will now apply optogenetics to stimulate specific elements in the retinal circuit to restore elementary visual processing in blind mice.”

Optogenetics is a wonderfully exciting field of research with a sci-fi feel that combines information and techniques from both optics and genetics to control brain cells. Basically, with the flip of a light switch, researchers are able to turn on (and off) brain cells. You can learn more about optogenetics in this cool video. We can’t wait to see the results from Dr. Awatramani’s new studies!

About the Study

The study was published in Neuron and is titled “Specific Wiring of Distinct Amacrine Cells in the Directionally Selective Retinal Circuit.” Research was conducted collaboratively by Alex Hoggarth, Amanda J. McLaughlin, Kara Ronellenfitch, Stuart Trenholm, Rishi Vasandani, Santhosh Sethuramanujam, and Gautam B. Awatramani from the University of Victoria, David Schwab from Northwestern University and Kevin L. Briggman from the National Institutes of Health.