What do neurons think about?

In my previous post I talked about Wilder Penfield and how he built a detailed map of the tactile cortex using the "straightforward" procedure of stimulating a specific area of the brain of a patient and asking the patient what he/she felt. This procedure follows a simple strategy: change something in the brain and observe (in this case ask) what happens. Many experiments follow this recipe by activating, deactivating, removing, anaesthetizing the part of the brain under study to try to elucidate its role.

A paradigmatic example of this kind of research is the case of Henry Gustav Molaison (or H. M.), who at the age of 27 (in 1957) underwent an experimental brain surgery that deprived him of a great part of his hippocampus (among other brain areas). After that surgery, H. M. was never able again to form new memories (yes, like the guy in Memento!) and thus became a unique "specimen" for the study of the role hippocampus plays in memory formation, which as we now know (partly thanks to Mr. Molaison) is critical. And so, again, you change something in the brain (in this case remove a whole area) and see what happens.

Before you get the wrong idea I should clarify that the reason why Dr. William Beecher Scoville, a neurosurgeon at Hartford Hospital (Connecticut), opened the skull of Mr. Molaison and removed a part of his brain was purely clinical. Molaison suffered severe epileptic seizures whose intensity did not decrease with any pharmacological treatment. This is one of the issues with the interventional procedure I have been talking about: too many times is pretty aggressive with the subject.

There is however another, usually simpler, way of investigating the brain though: you present a stimulus to the subject and observe what a given group neurons of your interest do in response. Many important discoveries in neuroscience have been achieved in this way. Here is a short story that exemplifies this alternative approach:

By the late 50's, one of the biggest questions in neuroscience, and in particular in the field of visual neuroscience, was what do neurons in the primary visual cortex (V1) respond to?? Neuroscientist knew that neurons in the retina (called retinal ganglion cells) and in the lateral geniculate nucleus (sometimes called relay cells) respond to changes in luminance (borders) with no specific orientation. In other words, these neurons, found in the first and second stage of the visual pathway, fire whenever they see a border, any type of border. But what happens in the third stage?? No one knew, but many people were working on figure it out. The usual experiment was as I described in the previous paragraph: you show a visual stimulus to the animal (normally a cat) and see what V1 neurons have to say about it. But the V1 neurons did not say much, they were not interested on the bright dots on a black background the scientist showed them.

Among these scientists, David Hubel and Torsten Wiesel were also trying to find The Stimulus. They had started working together almost by chance, in the laboratory of Stephen Kuffler, for what should have been a few months. In the end things got interesting and they ended up working together for 25 years. And (I guess) the main reason for this time miscalculation was that one day, after trying one thousand stimuli that did not cause any clear response in the neuron they were recording from, something happened: when one of them was changing the slide (they used slides projected on a screen to visually stimulate the cat) the neuron, the apparently mute neuron, fired. It fired a lot...

I can imagine the two scientists looking at each other, without moving a muscle:

- What did you do??

- I don't know!!

- Well... do it again!

- Do what?

- I don't know!!

Whatever their reaction was, they had just discovered the orientation selectivity that characterizes most of V1 neurons: they respond only to borders with a specific orientation. And they had done so by using the simple approach Show-and-Record I explained above.

Oh! I guess you are wondering why the neuron fired when they changed that slide and not any of the one thousand previous slides. The thing is that that slide was broken, it had a thin crack that let pass just a little bit of light, projecting in the screen a bright bar with the orientation to which that particular neuron responded to.

I guess you could call this luck, but maybe it would be more accurate to call it stubbornness.

Manuel Molano

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