December 5, 1996

Versatile man of vision

by Ellyn Kerr

Psychology professor Avi Chaudhuri

Avi Chaudhuri recognized good advice when he heard it. Chaudhuri, an assistant professor of psychology, completed his PhD at Berkeley under Donald Glaser, the 1960 Nobel laureate in physics, who counselled Chaudhuri to avoid limiting himself to one area of research. Chaudhuri heeded his mentor's words and is pursuing his scientific interest--the mechanisms of vision-following three separate avenues of investigation.

During his doctoral studies, he researched the visual perception of motion, using psychophysical techniques. Psychophysics treats the brain as a black box: subjects are presented with various stimuli and the subjects' responses are noted.

Chaudhuri went on to a postdoctoral position at the Salk Institute in San Diego. Here, he used electrophysiology to study the primate visual system, taking electrode recordings from the visual cortex (the area of the brain responsible for processing vision) while exposing the monkeys to various visual stimuli. He then worked as a research associate at University of British Columbia, where he acquired training in molecular biology.

"My interest is in how we process vision, but the tools that we use in my lab reflect my [diverse] history of study in this area: we're doing both visual psychophysics with human subjects, as well as molecular biology [on primate visual systems]. Even though these are poles apart in terms of technique, they're both used to address the same question: how it is that we see the visual world."

Chaudhuri's main research is to develop a diagnostic tool for early assessment of the colour blindness associated with glaucoma and diabetic retinopathy. Colour blindness, particularly to blue light, is often one of the first symptoms of these conditions.

Colour vision is mediated by retinal cells known as cones. Colour blindness is caused by the dysfunction of the cones responsible for detecting a particular colour.

"If you're blue colour blind, for example-if the blue cones are obliterated-then you're not going to see blue as vividly as would a blue-colour normal person. [Perception of blue, then, would require that blue objects emit more light, or be more luminous, than objects of other colours.] We've developed a technique which allows us to assess in colour-anomalous individuals the relative state of perceiving reds versus greens, or blues versus yellows, or any other pairs of colours."

Chaudhuri is refining for clinical use an experimental technique he previously developed to determine when a subject perceives two simultaneous colours to be equally bright. Many psychology experiments into assessing colour vision rely on a subject's perception of this equal brightness, or equiluminance.

Chaudhuri's technique consists of a computer-generated visual stimulus. A fine checkered pattern of two alternating colours is superimposed onto another pattern of shapes, such as dashes or dots.

The shapes are constantly moving in a particular direction on the computer screen, but this movement is obscured by an intentional flickering of the superimposed checkered colours when they are not equiluminant.

The subject or the experimenter can adjust the brightness of one of the two checkered colours. At the subject's perceived equiluminance point, the flickering of the colours wanes. The moving shapes that were obscured by the colours immediately become visible. The subject's eyes will reflexively follow the direction of the shapes' movement.

"When you see a large field moving in one direction, your eyes automatically follow it. It's a reflex, you can't control it. That's why this was a valid tool with monkeys. And because it's a non-verbal response, we can use it with babies, with people who are physically or cognitively challenged. It's a very efficient, quick and robust way to [assess the competency of retinal cones]."

With early detection of the colour blindness associated with glaucoma and diabetic retinopathy, clinical approaches to the treatment of these conditions could be facilitated.

This study is a collaborative effort with practitioners from the Jewish General Hospital: Julius Gomolin, a specialist in diabetic retinopathy; Oscar Kassner, a glaucoma specialist; and Olga Overbury, a clinical psychologist. The work is funded by the Medical Research Council.

The second avenue of Chaudhuri's research concerns the molecular basis of vision in primates. His lab has developed a novel technique for tracing the activity of neurons in response to visual stimuli.

Brain tissue in the visual cortex is organized into what are known as ocular dominance bands or columns. That is, a striated pattern exists where centres for inputs from the left eye alternate with centres for inputs from the right eye. Chaudhuri is applying his new technique to map the activity of these columns in the primate visual cortex.

A visual stimulus results in the activation of what are known as immediate-early genes (IEGs), starting a cascade of information processing throughout the visual cortex.

Chaudhuri applies probes to dissected visual cortex tissue, to determine which neurons have fired within each column in response to various stimuli. The "probes" he uses are small molecules which bind to the IEGs.

"We are excited about this because, for one, the technique allows visualization of response to more than one stimulus [previous methods only permitted visualization of neuron response to a single stimulus], and two, we can visualize activity at the cellular level. This will allow us to research all sorts of questions about the development and the function of the visual cortex."

This work is a collaboration with Joni Nissanov at Drexel University in Philadelphia, and is funded by a grant from the Medical Research Council.

In his third set of studies, funded by both the Natural Sciences and Engineering Research Council and the Alfred P. Sloan Foundation, Chaudhuri is examining the genetic differences between two types of brain tissue in the visual cortex, known as the M-stream and the P-stream.

The M-stream is believed to be involved in the processing of "fast" phenomena--for example, motion of objects in the visual field and coordination of eye movements, while the P-stream is thought to be involved in object and colour detection--cognitive processing of texture, shape and orientation. Chaudhuri's laboratory has been isolating and cloning genes expressed in the two streams of tissue.

"The underlying hypothesis is that the two systems, which have differences in cellular structure, [must stem from] genetic differences but nobody has studied that. In the past, the people who have engaged in this kind of work have been systems neuroscientists, who have looked at it from a systems level, not from a molecular perspective."

For Chaudhuri, the interdisciplinary scientific approach advocated by his mentor has been fruitful. "We're capitalizing on the molecular revolution to address questions that we couldn't address before, bridging two opposite ends of the neuroscience spectrum: the systems level at one end and the molecular at the other. It's been a lot of fun and it's working well."

Ellyn Kerr, currently pursuing a master's degree in biology, is a science writing intern for the Reporter, a project funded by NSERC.