Sight for sore eyes
If an animal has an eye kept closed from birth, after a few weeks, even if the eye is subsequently opened again, the brain nevertheless remains blind to input from that eye forever. The same happens in humans who were born with eye problems. If these aren't corrected quickly, the individual is destined never to see normally with that eye. UCSF scientist Michael Stryker has found a way to dramatically turn things around, as he explains to Chris Smith...
Michael - A few years ago, we discovered that when mice start to run, their cortex goes into a high gain state and in which the neurons respond much better. The question we wanted to ask in this paper was, whether this enhanced response would allow more neuroplasticity. That is, would allow the animals to change the way their brain responds much faster in response to a certain kind of activity. Would they learn better? Would they recover function in their visual system if their visual system had developed abnormally?
Chris - When you said they're in a high gain state, do you mean that literally, if you record from groups of nerve cells firing in the cortex, you see more firing or do you see bigger pulses, bigger amplitude?
Michael - We see more firing. More of the neurons fire much more strongly about twice as much when the cortex is in this state. We think this state might be important for things like attention. But at least in the mouse, their visual cortex goes into the state when the mouse starts to move through the world.
Chris - Part of me is wondering if this is the reason why some people - I mean, it sounds a bit lame, but some people say they like revising when they go for a jog and they'll listen to some learning tape and they'll say they remember more if they go jogging. Do you think the same apply to humans?
Michael - I don't know whether the same applies to humans and it's something we're tremendously interested and we're beginning to study now. Several of my colleagues tell me that they like to read papers on the treadmill because they remember them much better and understand them much more quickly.
Chris - I'm calling to mind the memories of medical school lecturers pacing up and down at the front of their lecture. You never see a lecturer stand still and as they're highly polished or a comedian stay in one place on a stage. they always walk around and one wonders whether this is playing out in the same way as your mice do.
Michael - I suspect that maybe because I feel the same thing when I lecture. I would much rather walk back and forth than point at various things and be physically active rather than to stand there like a statue.
Chris - So, what did you do with the mice because obviously, you can't get mice to give a lecture?
Michael - What we did with the mice was to feed them like children who were born with a congenital cataract in one eye that obscured the vision in one eye. And so, we took mice and closed one of their eyes for a period of several months and humans who grew up with a problem like this later, when the optical problem is corrected completely, later these people have lost the ability to see in that eye and are dramatically impaired when they try to look at the world through that eye. They're functionally and legally blind.
Chris - So, is this because something in their brain has changed which means their brain is essentially ignoring the visual input from that eye which it previously would've paid attention to?
Michael - Yes, most of the connections from that eye to the visual cortex are lost during a critical period in early life under these conditions. And so, the reason that people find it difficult to see is that their eye is not connecting properly to the brain anymore. The goal of our experiments in mice was to see whether these enhanced neuronal responses we see in the visual cortex during locomotion would allow them to recover much more vision and much stronger visual responses to the deprived eye.
Chris - And is that what you find so you get the mice doing more activity and compare them with mice to do less activity? Do you see that they'd get more functional recovery in the previously close eye?
Michael - They get dramatically more functional recovery. So that mice that get no special stimulation and stay in their home cage never recover more than halfway to normal whereas the mice that are allowed to run while they're getting high contrast visual stimulation, their vision recovers to near normal levels quite quickly within a week.
Chris - There's a central sort of tenet in your science which head put forward, which is that things that fire together, wire together. So, do you think that you've got every simple situation where you've just go enhanced firing because of the locomotion, the exercise, you present that with a very powerful visual stimulus, this is going to drive cells very hard as well so you've got the same cell firing with the locomotion and with the visual stimulus and the connections there are going to reinforce?
Michael - That's one of the possibilities and it's the one that I think is perhaps most likely. But another possibility is that when you'll have this exercise, you have more acetylcholine which is a chemical that affects neural transmission in neural cortex, you'll have more adrenalin. So, it's possible that some of these chemicals that are associated with these are the signals that mediate the greater plasticity. But the idea I favour is exactly the one you articulated.
Chris - And obviously one very important question from a sort of neuro rehabilitation perspective, if I took someone who had had a disabling stroke robbing them of one particular brain function, would the right thing to do be to repeat the experiment you've done with the mice, but with an appropriate stimulus relevant to their injury and see if you can get therefore enhanced recovery for them.
Michael - Well, that is the long term promise of this and at present, we just don't know whether that would help or not. We intend to study that, but at the present time, we really can't say whether that would be true or not..