Vivid insight

Professor Paul Martin has his eye on uncovering the complexities of primate colour vision.

It seems the most effortless thing to do: to gaze upon the canvas of the world splattered with a dazzling array of colours. Yet not every creature - or every person - sees the world in the same way. Colour is one of those things that require what philosopher Daniel Dennett calls a “strange inversion” in thinking. Colour is not ‘out there’ in the world; colour is very much a feature of what goes on ‘in here’.

And what goes on ‘in here’ depends to a great degree on the particulars of the neurobiology of vision: the ganglion cells in the retina; the neurones that pass through the thalamic relay nucleus, the lateral geniculate nucleus; the web of connections in the primary visual cortex; and the specialised processors of the higher cortex that discriminate the ‘where’ from the ‘what’.

It’s a spectacularly complex system, and while we have come a long way in unravelling the neurobiology of colour vision, there are still a few mysteries to tackle, or so says Professor Paul Martin from Sydney University and the Save Sight Institute. He will be giving this year’s Lawrie Austin Lecture at the 33rd Annual Meeting of the Australian Neuroscience Society, in Melbourne in February.

Given the complexity of the visual system, we know a surprising amount about how it functions. It starts with the photosensitive rods and cones that we all learnt about in high school. They trigger a cascade of nerve impulses in response to light, which careen through the lateral geniculate nucleus, or LGN, via two main pathways, the parvocelluar and the magnocellular. The parvocelluar cells respond to colour and fine details and edges, while the magnocellular cells provide the depth and motion.

These signals then travel to the primary visual cortex where the signals are synthesised to pick out edges and shapes. The final stage of the process sees the signals sent to other regions of the cortex that hone in on the identity and position of the visible objects. And somewhere in there, a holistic picture emerges, replete with colour, discrete objects and all in a seamless, conscious experience.

Except it’s not quite so simple, says Martin. Firstly, the parvocellular/magnocellular pathway story is proving to be overly simplistic. It seems the pathways interact and overlap in their function with another pathway in order to produce a complete picture, as it were. “We’re gradually starting to tease out where these pathways go,” says Martin.

“We used to think the parvocellular and the magnocellular pathways did the whole job, but now we have strong evidence that the so-called primitive pathway, which also serves visual reflexes, actually has signals that seem related to conscious visual perception.”

This primitive pathway is the koniocellular pathway. Martin and his team found that this pathway exhibits ‘rhythms’ in individuals who are asleep or under anaesthesia, and they have speculated that it plays a significant role in coordinating activity between cortical and subcortical brain structures.

“It is actually an old anatomical theory that we picked up on, that the koniocellular division is part of a primitive pathway that it acts like the rhythm section in a rock band. They’re the foundation on which the rest of it works. The rhythm section may not be the biggest part of the band, but it’s a very important part.”

Two-way street

The second spanner in the works is the idea that the visual system is a one-way street, beginning with the eye and ending in the cul-de-sac of the higher cortex. In reality, it appears there are some fascinating feedback cycles involved throughout the process that is changing the way we think about vision.

“We used to think of it as a one-way street,” says Martin. “There’s the front end in the eye, then you go through the thalamus, then through to the cortex, and one part of the cortex feeds to the next. Eventually you hone down to more and more complex features within the cortex.

“Yet what we’ve found is that at every level - once you get out of the eye - each higher level isn’t really higher because it feeds back to the lower level, so it influences its own input. So it’s really a two-way street, not a one-way street. It’s not just commands that are going from one place to another, but it’s more like a conversation.”

Interestingly, according to Martin, this is an insight that has been known in anatomy for many decades, but it’s only recently that the more complex physiology of the process has started to be revealed in any detail.

So why the back-and-forth? Martin believes it could be something to do with directing attention. We absorb a truly vast amount of visual information by staring at a single scene, yet we’re able to direct our conscious focus around without changing our visual focus, as it were. The backward path may be the higher cortex directing attention on to particular parts of what we’re observing.

Many rainbows

Then there’s colour. How the brain teases apart the various signals flowing down the different pathways to construct a seamlessly, yet context-sensitive, polychromatic picture is another deep mystery that is slowly being unravelled. One piece of the puzzle that is helping bring context to the story is looking at the evolution of trichromatic colour vision.

Martin works with marmosets, a species of monkey in which all males are red-green colour blind, while most females are trichromats like us. These monkeys may represent something of a stepping stone between the lower dichromatic primates and the upper primates with full trichromatic colour vision, and understanding how their visual system works might give us insight into the system from which ours developed.

According to Martin, one popular theory is that there was a mutation on the X chromosome that enabled females to develop trichromatic vision, and this may have given them a selective advantage when it came to navigating their environment or identifying edible fruits. The evolutionary trick was in getting that mutation over to the males, as it occurred on the X chromosome.

“The males are all colour blind because they haven’t got the two genes on their X chromosome. Females, on the other hand, have two X chromosomes, and if they have red on one and green on other, then they can have three receptors. The males are stuck with two, just like in many humans with colour blindness.”

But what happens when that mutation occurs, adding a third type of photoreceptor sensitive to red light? Can the brain suddenly create trichromatic vision without any further changes? A 2009 experiment by Professors Jay and Maureen Neitz at the University of Washington suggests it can.

They injected a virus into the eyes of the monkeys that contained a gene that produced L-opsin, a protein lacked by the monkeys that is involved in detecting red and green. Startlingly, around five months after the treatment began, the monkeys appeared to be able to consistently discriminate red from green overnight. It was like a penny had suddenly dropped and they saw the world in an entirely different way.

What was especially intriguing is that this change didn’t appear to require any significant rewiring of the higher cortex. Instead, once the red-green signals were sent down different pathways, the brain began discriminating between them and the distinction between the colours emerged.

“When the paper was published, Jay Neitz told me there were people queuing outside his laboratory door asking for him to give them the needle,” says Martin. Yet the gene therapy is still some way from being ready to potentially address colour blindness in humans - although, in principle, it should work.

What excites Martin is the prospect of treating a whole slew of diseases once we gain a greater understanding of our colour visual system. “Certainly, the potential of this gene therapy is there to treat colour blindness,” he says. “But from the perspective of a vision scientist, and someone who thinks about other blinding diseases, the same method they used to get colour genes could be used to fix the cells in other ways. You could package up other restorative genes to fix up diseases such as retinal dystrophy, where the receptors degenerate, for example.”

Yet, even with the tremendous progress over the last few decades in uncovering the internal machination that produces colour vision, there are still a lot of mysteries yet to be solved. Martin and his team are currently delving deeper into the koniocellular pathway and investigating how it contributes to colour vision and brain rhythms.

They are also taking a closer look at the macula, with an eye - as it were - to determining the similarities with the monkey macula. This is particularly important if, for example, the gene therapy that worked in monkeys is to be translated into a human treatment.

Professor Paul Martin received his PhD in Physiology at the University of Sydney in 1986. In 1992 he returned to join faculty at the University of Sydney following postdoctoral work in Germany. In 2003 he left Sydney to take up appointment as Director of Research at the National Vision Research Institute of Australia and Professorial Research Fellow at the University of Melbourne. He returned to Sydney in 2010 to take up his current appointment as Professor of Experimental Ophthalmology.