#SfN12 Tipping the memory scale

Post-learning increase in adult hippocampal neurogenesis leads to forgetting

*K. G. AKERS, A. MARTINEZ-CANABAL, A. L. WHEELER, L. A. RESTIVO, A. J. GUSKJOLEN, H. SHOJI, T. MIYAKAWA, S. A. JOSSELYN, P. W. FRANKLAND

New neurons are constantly produced in the brain, where they slowly mature and integrate with existing neurons into neural networks. While the precise function of these new neurons are not very well understood, researchers believe that they may be part of the reason why anti-depressants work. Theses adult-generated neurons also seem to be involved in boosting memory performance – after all,  the more computational units, the more computing power, right? Along this line of thought, may labs have shown that if you artificially enhance neurogenesis through exercise or anti-depressant administration in rats, they are able to separate two very similar memories better.

However, newly generated neurons can also disrupt existing neuronal networks when they integrate into an existing network. Since established memories are stored in these networks, it is conceivable that old memories may be disrupted during enhanced neurogenesis.

To show this, researchers exposed adult rats to a certain room, waited for 28 days before putting the rats back into the room and shocking them with an electrical zap. During the wait, one group of rats were allowed to chill out as usual, while the other was subjected to an intense running regime, which has previously been show to increase the production and survival of new neurons. After the shock, the rats were put back into the room to see whether they remembered it as a “bad” place, which can be measured by how much they froze. This is called one-trial learning. Since the rats were shocked only once immediately after being placed in the room, for them to actually associate the room with the shock, they would need to remember that they had previously seen the room 28 days ago. Hence, if they freeze, it would mean that they still retained the memory of the room 28 days later.

What was surprising was that the running rats showed less freezing, meaning that they had harder trouble remembering the room than rats that didn’t run. This seems to suggest that running-induced increase in new neurons disrupted the memory of the room.

If this were true, other methods that increase neurogenesis would show the same trend. And indeed, when adult rats where given certain drugs that help the brain produce more neurons (such as fluoxetine, the antidepressant), the adult rats showed less freezing, hence less memory of the room in which they were shocked.

Young animals have a much higher rate of neurogenesis than adult rats. Since the neural networks are constantly being built and destroyed in young animals, the researchers reasoned that decreasing neurogenesis in young rats could help stabilize an existing memory. The researchers trained a group of infant rats in the same task, and showed that indeed, a drug that slowed the production of new neurons led to an increase in the retention of the memory of the room.

So if new neurons disrupt old memories, how is this beneficial to a young animal?  Infants are bombarded constantly with new information, and it makes sense to update an existing association when the old memory is no longer true. To test this, the researchers trained rats on a Morris Water Maze task, where the rats had to swim in a big tub of milk until they found a hidden platform to rest on.  As before, the rats that had more new neurons had a tougher time finding the platform, meaning they remembered its location less clearly. However, when the researchers sneakily moved the platform to a new location, the rats with increased neurogenesis learned faster, suggesting they were better able to update their memory.

This is a super cool study showing that increased production of new neurons may not benefit memory per se, but is more important in allowing memory flexibility.

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