We summer in Woods Hole (when our house is not rented, which is most of the summer) and occasionally can go to one of the Friday night public science lectures at the Marine Biological Laboratory, the world-famous research facility in Woods Hole. It is a magnificent privilege to hear and see world-class scientists give beautiful slide lectures on fascinating, cutting-edge science.
On occasion, when the lecture is particularly clear and my brain is fresh, I can go home and write down the gist of the lecture. So since I haven’t posted anything for almost a month, I dug up one of these writeups.
MBL LECTURE 19 JULY 2013
The lecturer, a famous Chinese neuroscientist Mu-Ming Poo, around 70, spoke on neural plasticity.
He started with a much-cited quote by the famous neuroscientist Donald Hebb, to the effect that neurons that fire together wire together, forming more or less permanent circuits – i.e. memories. This is a qualitative statement; Poo and his colleagues sought to explore it quantitatively.
He asked how close together in time the two firings had to be in order to create a memory. He found that the window generally was 40 milliseconds wide, with exceptions in certain animals. He also asked whether the sequence mattered (i.e. what happened if the second neuron fired before the first one), and he found that when the sequence was reversed, exactly the opposite effect occurred: the two neurons became less likely to fire together than previously.
Background: neurons collect inputs from “dendrites”, sum them in complicated ways, and if the incoming stimulus is sufficient, they fire. The electrical signal runs rapidly down the cell’s axon (at about 45 mph), which is the long “wire” that carries the electrical charge from the cell to the other cells to which it is connected, when the cell fires. During development, each neuron seeks out and finds the neurons in the part of the brain to which it “should” be connected. Retinal cells connect via intermediate links to cells in the visual cortex, which in humans is located at the back of the brain (“cortex” is the thin grey-colored coating of neurons on the outer surface of the convoluted brain). Back to the lecture.
To understand why the 40 millisecond window is adaptive, imagine a row of adjacent retinal cells. Each retinal cell connects with a large number of cortical cells in the visual cortex that are adjacent to one another. Call the retinal cells “A” and the cortical cells “B.” This means that each B cell receives inputs from a lot of A cells. So the image created by one A cell is spread out and blurred in the visual cortex.
The goal is to create a sharply focused “map” on the visual cortex that matches the image falling on the retina. To accomplish this, the brain needs to prune away connections between A cells and distant B cells, and strengthen connections between A cells and B cells that are close together.
Imagine a moving spot falling on the retina and hitting one A cell. The A cell will fire and cause all the B cells to which it is connected to fire. Since the B cells fire together within the 40 millisecond window, with the A cell firing first, the connections are strengthened. Now the spot moves to the next A cell (it is moving fast). Again the A cell sets off all the B cells to which it is connected. But some of these will already have fired during the previous 40 millisecond window mentioned above. In those cases, the B cell has fired before the A cell, which weakens the connection. Over many occurrences, this process sharpens the map in the visual cortex.
In the second example of neural plasticity, he explored how mature neurons in a frog’s brain form short term memory by training a string of neurons to fire in sequence. Remarkably, there are instruments that can probe individual neurons in a living animal brain, as well as a brain in a petri dish (in vitro – glass – as opposed to in vivo – life). First the investigators associated neurons in the retina with the corresponding neurons in the visual cortex. Then they passed a moving spot over the retinal cells and noted that the cortical cells lit up one after the other.
After doing this many times, training the cells, they then stimulated just the first retinal cell, which caused the string of cells in the visual cortex to fire one after the other. The neurons had learned that the spot moves on this particular track (this is short term memory, lasting only about 10 minutes). When they stimulated the last cell in the sequence, nothing happened. They then stimulated the cortical cells directly, and the same thing happened, showing that it was the cortical neurons that learned and not the retinal cells.
In a third demonstration, they found that cells in a zebra-fish could remember the timing between sequential stimuli. This became evident because if they stimulated the cells five times or more, the cells fired one more time after the stimulus was removed at exactly the same interval as the initial sequence. This occurred at intervals up to about 10 seconds. The larger the number of sequential stimuli the more firings occurred after the stimuli stopped, but only up to 3 repetitions. He showed a movie in which the stimuli caused the tail of the fish to twitch to the side (an escape behavior), and sure enough, after the stimuli ceased, the tail twitched twice at exactly the same interval as the stimuli.
Finally, it was believed that only humans and some apes could recognize themselves in a mirror and that monkeys could not. He experimented with Rhesus monkeys. If you paint a spot on the monkey’s face (or even shine a light at the spot so he doesn’t feel anything) he ignores it when looking in the mirror, showing that he is not aware that the image is of himself.
So Poo did a clever thing: he applied the spot in a way that irritated the same location on the monkey’s face, which caused the monkey to reach up and touch the spot. By doing this many times, he trained the monkey to associate the two spots and thereby become aware that the image in the mirror was himself. Once they learned this (2 out of 3 could do so) they took advantage of their new skill by examining parts of themselves that they couldn’t see (their bottoms). It was hilarious to see the contortions they went into in order to inspect their nether regions.