Fly sex study may unlock the secret to maintaining long-term memories

Memories begin as fleeting experiences that register temporarily in our brains. With time, sleep, and deliberate practice, those short-term memories blossom into long-term recollections. But in order for those long-term memories to grow, scientists think we may need one additional and and unconventional ingredient.

Early-stage research on copulating fruit flies suggests that light plays an essential role in transforming short-term memories into long-term ones. A team of researchers in Japan found that the fruit fly brain contains a pathway of “memory maintenance” proteins that seemingly activate when the flies are exposed to normal day and night periods, but not when they’re kept in total darkness.

The study was published this week in The Journal of Neuroscience.

"We can not deny the possibility that light is needed for long term memory maintenance in humans, although it still remains unknown.”

The study’s lead author Takaomi Sakai, an assistant professor at Tokyo Metropolitan University, says this is the first time that scientists have proven that light is “essential” for the maintenance of long-term memory.

While the fruit fly brain isn’t comparable to a human brain (or even a mouse brain), this finding does suggest that there could be parallel systems in our brains that have yet to be uncovered. 

“Molecular mechanisms associated with learning and memory seem to be conserved across animal species,” Sakai tells Inverse. “Thus, we cannot deny the possibility that light is needed for long term memory maintenance in humans, although it still remains unknown.”

Fruit fly sex and long-term memory

Fruit flies don’t have to remember long lists of to-dos, nor do they really care about mastering new skills. Instead, what they really care about is getting it on.

Fruit fly sex is incredibly metal and competitive, which means that it’s essential that flies learn how to make their romances count.

In this study, the scientists capitalized on the brutal nature of fruit fly sex by exposing males to “nonreceptive females” for seven hours. Fresh off of seven hours of rejection, the scientists discovered that the males tended to seek out virgin female fruit flies, realizing that they were the most receptive to their advances.

Days later, the team put the flies’ memories to the test by measuring how long they maintained their virgin-seeking behavior.

However, before the test day they conducted an essential part of the experiment: Some of these flies were kept in total darkness during a two day “maintenance period.” This is when their brains underwent the process of solidifying that rejection experience into an informative memory. Meanwhile, other flies were exposed to constant light, and a final group was exposed to a normal day-night cycle.

The team found that the flies kept in total darkness had “severe” long term memory impairments, whereas those exposed to light had their memories intact. In follow-up experiments, the team showed that light appears to be the reason the flies kept in darkness struggled to maintain their memories.

Ingredients that memories need to grow

To transition from short-term memory to long-term memory, memories require “continual maintenance” says Sakai. Among humans, that maintenance comes down to your own efforts, along with some molecular housekeeping in the brain.

For instance: Sleep is powerful for memory consolidation because it can help the brain prune unnecessary memories, rebalance synapses in the brain to promote learning, and help the brain load up microRNAs, which facilitate memory consolidation.

Since sleep is also important for memory formation in fruit flies, it’s plausible that keeping flies in total darkness would impact their sleep, and as a consequence, their memories too. The flies who were kept in darkness slept less than those kept in normal light cycles.

However, the team also found that when they deprived the flies kept in normal light cycles of sleep, their long-term memory didn’t decline.

That finding suggests that the flies kept in darkness had additional burdens placed on their long-term memory — perhaps, the darkness itself. This indicates that light, like sleep, also sets a pathway of memory-related protein signaling in motion.

When the team analyzed neurons in the fruit fly brains, they found that light exposure promotes the release of a peptide called “Pigment-dispersing factor” (Pdf). Pdf, Sakai, explains is essentially a neurotransmitter in the fly brain. That release of Pdf promotes the expression of genes in the brain’s memory center.

Importantly, when the the team artificially released Pdf in the brains of flies kept in darkness, their long term memories were maintained. These genes that are transcribed because of Pdf release are “required” for maintaining long term memories in flies, Sakai argues.

The open question is whether light will prove as essential for memory in other species. On one hand, the authors note that the pathway is highly evolutionarily conserved, which means that other species could have something similar to it.

What’s next?

One peptide that the team thinks should be examined in the future is the Vasoactive intestinal peptide (VIP). VIP is commonly found in neurons that make up the suprachiasmatic nucleus (SCN), the light-sensitive area of the brain that controls circadian rhythm.

Sakai explains that the VIP conserved in mammalians species “has Pdf-like functions.”

Following that chain of logic, it’s possible that this team’s findings could explain more than the fly brain. For now, Sakai says the next step is to figure how what genes that Pdf seems to impact affect fruit flies. If those seem to have corollaries in humans, they may prove to be essential ingredients that help our memories take root in the brain.

If that turns out to be true, exposure to light could one day prove to be as important in a daily schedule as sleep already is.

Abstract:

Long-term memory (LTM) is stored as functional modifications of relevant neural circuits in the brain. A large body of evidence indicates that the initial establishment of such modifications through the process known as memory consolidation requires learning-dependent transcriptional activation and de novo protein synthesis. However, it remains poorly understood how the consolidated memory is maintained for a long period in the brain, despite constant turnover of molecular substrates. Using the Drosophila courtship conditioning assay of adult males as a memory paradigm, here, we show that in Drosophila, environmental light plays a critical role in LTM maintenance. LTM is impaired when flies are kept in constant darkness (DD) during the memory maintenance phase. Because light activates the brain neurons expressing the neuropeptide Pigment-dispersing factor (Pdf), we examined the possible involvement of Pdf neurons in LTM maintenance. Temporal activation of Pdf neurons compensated for the DD- dependent LTM impairment, whereas temporal knockdown of Pdf during the memory maintenance phase impaired LTM in light–dark cycles. Furthermore, we demonstrated that the transcription factor cAMP response element-binding protein (CREB) is required in the memory center, namely, the mushroom bodies (MBs), for LTM maintenance, and Pdf signaling regulates light-dependent transcription via CREB. Our results demonstrate for the first time that universally available environmental light plays a critical role in LTM maintenance by activating the evolutionarily conserved memory modulator CREB in MBs via the Pdf signaling pathway.