UC Berkeley scientists detail neural circuit that lets eye detect directional motion

Nearly 40 years ago scientists were startled to discover that the eye, far from being a still camera, actually has cells that respond to movement. Moreover, these cells are specialized to respond to movement in one direction only, such as left to right or right to left.

Now, in a paper in this week’s issue of the journal Nature, biologists at the University of California, Berkeley, have finally detailed the cellular circuit responsible for motion detection in the eye’s retina.

This circuit, which enables us to track moving objects, serves as an example of other brain circuits, some of which perform thousands of computations every second. The findings could aid the design of bionic eyes that track motion and process visual information like our own eyes.

“This work reveals a very sophisticated neural computation, the first non-linear computation performed by the nervous system for which a circuit is close to being solved,” said Frank Werblin, professor of molecular and cell biology at UC Berkeley. “It is a preliminary step in understanding how more sophisticated computations are performed by the brain.”

Werblin notes, for example, that we use motion detection every time we cross the street, anticipating when traffic will reach our intersection and deciding when to cross.

“Barry Bonds probably has superior motion-detecting neurons,” he added, referring to the home-run hitter with the San Francisco Giants. “He takes a simple movement detector and, in the context of a highly sophisticated action, uses it, along with about a million other computations, both sensory and motor, to make contact with the ball.”

The technically demanding experiments measuring the output of cells in the retina were conducted in Werblin’s laboratory by graduate students Shelley I. Fried of the School of Optometry’s Graduate Group in Vision Science and Thomas A. Münch of the Helen Wills Neuroscience Institute. All are members of UC Berkeley’s Health Sciences Initiative, a group of hundreds of basic researchers banded together to tackle some of the major health problems of the 21st century.

Horace Barlow was at UC Berkeley in 1965 when he and colleague William Levick noticed that some cells in the retina of rabbits fired only when a light moved through the eye’s field of view. A stationary light generated minimal response from these cells except when blinking on or off.

In further experiments at UC Berkeley and, later, Cambridge University, Barlow showed that some cells fire only when a target moves from left to right, others fire only when a target moves right to left, and still others respond only to up-down or down-up movement. These cells activate the four sets of muscles that control eye movement and allow close tracking of moving objects. But the signals also make their way through the optic nerve to the brain, providing dynamic detail of the physical world.

Since these early experiments, scientists have discovered cells in the retina that respond best to moving edges or to moving edges of a particular orientation. There may be a dozen or more types of these specialized ganglion cells. The cells’ axons – the outgoing wires of the neuron – bundle together to form the optic nerve that funnels visual information to the brain. Werblin and his laboratory colleagues have been probing these cells in the retina, and building computer models that help them understand how the physical world is reconstructed by the eye and the brain into a picture of our surroundings. Their findings have gone into the design of a bionic eye that employs a unique computer chip that can be programmed to do visual processing just like the retina.

Barlow’s original explanation of why directionally selective cells fire only in response to movement in one direction were very general, and recent experiments have confused the picture even more. The UC Berkeley team has laid out nearly the whole circuit, which includes three separate and redundant mechanisms in the retina that work together to create a directionally selective output.

“When Horace Barlow discovered that signals from some cells specified the direction of movement, he tried to explain it, and his explanation has been the reigning assumption,” Werblin said “He was right in general outline, but his explanation contained a lot of black boxes. We’ve shown what’s going on in the boxes.”

The basic light detectors in the retina are the photoreceptors, which fire off signals to a layer of horizontal cells and thence to bipolar cells. The bipolar cells funnel signals down their axons and relay them to the dendrites, or input wires, of ganglion cells, which send the processed information to the brain. All these cell types are arrayed in unique layers, stacked one atop the other in the retina. At the bottom of the stack are the 12 or so different kinds of ganglion cells, including the directionally selective ganglion cells.

If there were no other cells types, light shining on a photoreceptor would initiate a signal that cascades unaltered through the cell layers to the ganglion cell, and then into the brain. But other cells, called amacrine cells, weave among the bipolar cell axons and alter their output. This is what makes some ganglion cells respond to motion in one direction only.

Fried, Münch and Werblin showed that the key player in detecting motion is an amacrine cell dubbed a starburst cell, because its dendrites spread out from the cell center in a spoke-like pattern that suggests a figurative starburst.

The UC Berkeley team developed a technique to measure not only the firing of the directionally selective ganglion cells, but also the input these cells receive from starburst and bipolar cells. In contrast to a recent paper suggesting that starburst cells are not crucial to detecting directional motion, they found them to be the critical link.

“The problem is that there are directionally selective cells and starburst cells everywhere, and you can’t tell which are connected,” Münch said.

By probing this section of the retina, they discovered that directionally sensitive cells are connected to only half of the 60-70 starburst cells within their reach. All of these are on one side only, an asymmetry that allows them to veto firing when a stimulus comes from that direction.

Starburst cells not only affect directionally sensitive ganglion cells, they also reach out and touch bipolar cells. This allows starburst cells to alter the firing of bipolar cells, too.

As a result, when a target moves in the “preferred” direction – the direction that causes directionally sensitive ganglion cells to fire – the ganglion cells get a strong stimulus from bipolar cells and reduced inhibition from starburst cells. The cumulative effect is a stimulus that triggers the ganglion cell to send a signal to the brain.

When a target moves in the “null” direction, starburst cells inhibit firing and also veto the excitation from bipolar cells. The net effect is strong inhibition and no firing of the directionally selective ganglion cells. Also, because the inhibition from starburst cells arrives before any excitation from the bipolar cells, firing is diminished even more.

“Starburst cells not only shut off the output of bipolar cells, they also deliver negative input to the ganglion cells,” Fried said.

One unexpected finding was that starburst cells themselves are sensitive to the direction of a moving stimulus. They emit more neurotransmitter when a target moves outward along a dendrite than when it moves inward toward the cell body, creating a third mechanism by which they can signal direction of movement.

“The original problem was, how do directionally selective cells work,” Werblin said. “Now we want to know how the processes of starburst cells are selective.”

The work was supported by grants from the Office of Naval Research and the National Institutes of Health.