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By Sara

Starving Flies Must Shut Down Long-Term Memories or Die

Here’s something that people often forget about memories—they are expensive. Whenever we create new ones, and possibly whenever we recall old memories, our brain needs to manufacture new proteins in its neurons. This consumes a lot of energy, which partly explains why the brain demands proportionally more fuel than other organ. And even if we’re short of energy, the brain gets first dibs.

But the brain can also prioritise its various jobs. By studying flies, Pierre-Yves Placais and Thomas Preat from the CNRS in Paris found that starving individuals disable the creation of unpleasant long-term memories.

Such memories might be a useful investment for the future, but the starving flies are about to die right now. Laying down expensive memories is a luxury they cannot afford, and if Placais and Preat forced them to do so, they died faster. For the flies, building certain memories actually compromised their survival—a striking reminder that the brain is subject to the same fine checks and balances that the rest of the body obeys.

Placais and Preat trained flies to associate a smell with an electric shock, and then exposed them to cycloheximide—a chemical that stops the brain from building the proteins necessary for long-term memory. If the flies had been fed, the chemical worsened their memories, as expected. But if they hadn’t eaten for 24 hours, cycloheximide did nothing. Likewise, mutant flies that find it hard to build long-term memories were worse than normal flies at learning about the electric shocks, but only if they were fed. If they were hungry, their genetic disadvantage didn’t matter.

It’s not that the hungry flies were stressed and just feeling mentally slower all round. Their condition didn’t affect another type of memory that is shorter-term, cheaper, and does not depend on making new proteins. Instead, they were responding to their hunger by adaptively shutting down one very specific type of memory.

Flies depend on two special neurons to make long-term memories, and Placais and Preat found that both of these are unusually silent when the insects are starving. The duo deliberately activated these neurons by infusing them with temperature-sensitive proteins, which made them fire at anything above 28 Celsius. When this happened, the starved flies regained the ability to make enduring memories.

But they paid a heavy cost. By forcibly bringing the flies’ disabled memories back online, Placais and Preat shortened their lives by about a third. This only happened if they were trained to link the shocks and the smells. If they were exposed to only smells, or only shocks, or given nothing at all to learn, they were fine. It was the combination of training and memory-making that doomed them.

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The fruit fly Drosophila melanogaster, by George Novak

These results fit with earlier work from Swiss scientist Frederic Mery. He showed that flies that make long-term memories are more vulnerable to harsh environments, and that breeding male flies to have better long-term memory also shortens their lives. “It’s very surprising that things are apparently so clean and simple,” says Preat. “If the animal is starved, the brain blocks LTM formation; otherwise, death occurs faster.”

But of course, things aren’t quite that simple. Starving flies can still make long-term memories of pleasant experiences, such as linking smells with food. Indeed, these “appetitive memories” only seem to form if flies are hungry, which is why scientists who run experiments involving such memories have to starve their insects first. This makes sense. Flies only get the chance to build appetitive memories once they’ve actually found some food, so they can immediately pay the energetic cost of making fresh proteins. It’s only “aversive memories” of unpleasant experiences that aren’t worth creating.

Meanwhile, over in Japan, Yukinori Hirano was running a similar set of studies at the Tokyo Metropolitan Institute of Medical Science that complement but complicate the results from the French team. He found that fasting improves long-term memory in flies, but only if the insects go hungry for less than 16 hours. Any longer, and those same memories shut down, as in Placais and Preat’s experiment.

And the surprises kept coming. Hirano found that this improved long-term memory is actually different from the vanilla version that the flies normally use—it forms after a single round of training but decays after a shorter time. These two flavours of long-term memory also depend on different (if slightly overlapping) sets of molecules and neurons.

The two studies paint a complicated picture, but both support a single core theme: Flies can prioritise different types of memory depending on how hungry they are.

And the obvious million-dollar question: Does we and other mammals do the same thing? Both teams are trying to find out, but they think the answer is yes. “It’s very likely because all the basic mechanisms of brain functioning have been conserved during evolution,” says Preat.

Reference: Placais & Preat. To Favor Survival Under Food Shortage, the Brain Disables Costly Memory. http://dx.doi.org/10.1126/science.1226018

Hirano, Masuda, Naganos, Matsuno, Ueno, Miyashita, Horiuchi & Saitoe. 2013. Fasting Launches CRTC to Facilitate Long-Term Memory Formation in Drosophila. http://dx.doi.org/10.1126/science.1227170

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