Nav: Home

Learning from experience is all in the timing

June 26, 2019

As animals explore their environment, they learn to master it. By discovering what sounds tend to precede predatorial attack, for example, or what smells predict dinner, they develop a kind of biological clairvoyance--a way to anticipate what's coming next, based on what has already transpired. Now, Rockefeller scientists have found that an animal's education relies not only on what experiences it acquires, but also on when it acquires them.

Studying fruit flies, the researchers showed that a single odor can become either appealing or disgusting to an animal, depending on when the smell is encountered relative to a reward. The study, described in a report in Cell, also reveals that animals can quickly revise these memories, and shows how this process unfolds on a cellular level--insights that likely pertain not just to flies, but to learning across the animal kingdom.

Which came first?

Memory, at its most fundamental level, amounts to a series of associations: Ring a bell before feeding a dog, and eventually the dog will learn to salivate at the sound of the bell alone.

"In this case, the bell comes before the food and is therefore predictive of reward," says Annie Handler, a graduate fellow in the lab of Vanessa Ruta, the Gabrielle H. Reem and Herbert J. Kayden Associate Professor. "But we suspected that there isn't just one order of events that animals find significant. They should also be able extract meaning from cues that follow a reward."

For example, if a dog hears a bell after its meal concludes, then it should develop a negative association with that sound, as it signifies the end of chow. Hoping to better understand how timing affects memory, Ruta and Handler examined the brains and behavior of fruit flies.

Rather than supply the animals with tasty treats, the researchers used a technique called optogenetics to stimulate neurons that normally become active when an animal receives a reward, an approach that allowed them to precisely control the timing of positive feedback. They found that if these neurons were stimulated immediately after an otherwise neutral odor, the flies developed an attraction to that smell. Conversely, if they activated the neurons just before exposing flies to the same odor, the animals began to avoid it.

"The difference in time is only one or two seconds, yet the flies form completely opposing associations," says Handler. "Somewhere in the brain that difference of a second--of whether the odor comes before or after the reward--makes a huge difference."

The fact that brains have a sense of timing may seem intuitive; but exactly how neurons encode the sequence of events on a cellular level is far from obvious. Relatively small and simple, the fly brain offers a unique opportunity to study the neural circuits underlying this phenomenon--and that's exactly what Ruta and Handler did.

Remaking memories

To determine how flies discriminate the timing of events, the researchers monitored changes in a brain region called the mushroom body. Known to be involved in associative learning, this area contains Kenyon cells, which carry odor signals, dopamine neurons, which carry reward signals, and output neurons that regulate a fly's attraction to an odor.

Kenyon cells can be either strongly or weakly connected to output neurons; and dopamine tunes the strength of these connections, or synapses. If a Kenyon cell detecting a specific odor forms a weak connection with an output neuron, the animal becomes attracted to that odor; if this synapse grows stronger, however, the smell will become meaningless, or even aversive to the animal. Analyzing this type of connection, Ruta and Handler identified a signaling pathway that can either strengthen or weaken synapses, depending on the precise moment when dopamine neurons become active.

"This pathway is time sensitive, so whether the dopamine neuron is activated before or after an odor makes a critical difference in the strength of connections between cells in the mushroom body," says Ruta. "And we believe this is the mechanism by which the brain figures out the sequence of events."

By tinkering with this pathway, the researchers also found that they could quickly make strong synapses weak and vice versa, suggesting that memories can be erased just as quickly as they're formed. And when they analyzed fly behavior, they found further evidence of the ability to revise mental associations.

"We performed 50 trials. Each time we switched the timing of the odor relative to the reward; and each time the animal became more or less attracted to the odor, depending on what it had experienced a minute prior," says Handler.

In other words, even if a fly had previously learned to associate an odor with reward, it could quickly unlearn that association if the smell failed to predict reward in future trials. Memories are not set in stone; rather, they're set in synapses, which can be modified as an animal's environment and experiences change. Indeed, this experiment highlights that survival depends not just on the ability to form memories, but also to forget them.

"There are so many things that we could remember on a daily basis, so we hold on to the memories that turn out to be predictive; and we toss out associations that are incorrect or irrelevant," says Ruta. "When you live in a dynamic environment--which both flies and humans do--that seems like a very good strategy."

Rockefeller University

Related Neurons Articles:

How do we get so many different types of neurons in our brain?
SMU (Southern Methodist University) researchers have discovered another layer of complexity in gene expression, which could help explain how we're able to have so many billions of neurons in our brain.
These neurons affect how much you do, or don't, want to eat
University of Arizona researchers have identified a network of neurons that coordinate with other brain regions to influence eating behaviors.
Mood neurons mature during adolescence
Researchers have discovered a mysterious group of neurons in the amygdala -- a key center for emotional processing in the brain -- that stay in an immature, prenatal developmental state throughout childhood.
Astrocytes protect neurons from toxic buildup
Neurons off-load toxic by-products to astrocytes, which process and recycle them.
Connecting neurons in the brain
Leuven researchers uncover new mechanisms of brain development that determine when, where and how strongly distinct brain cells interconnect.
The salt-craving neurons
Pass the potato chips, please! New research discovers neural circuits that regulate craving and satiation for salty tastes.
When neurons are out of shape, antidepressants may not work
Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed medication for major depressive disorder (MDD), yet scientists still do not understand why the treatment does not work in nearly thirty percent of patients with MDD.
Losing neurons can sometimes not be that bad
Current thinking about Alzheimer's disease is that neuronal cell death in the brain is to blame for the cognitive havoc caused by the disease.
Neurons that fire together, don't always wire together
As the adage goes 'neurons that fire together, wire together,' but a new paper published today in Neuron demonstrates that, in addition to response similarity, projection target also constrains local connectivity.
Scientists accidentally reprogram mature mouse GABA neurons into dopaminergic-like neurons
Attempting to make dopamine-producing neurons out of glial cells in mouse brains, a group of researchers instead converted mature inhibitory neurons into dopaminergic cells.
More Neurons News and Neurons Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Why do we revere risk-takers, even when their actions terrify us? Why are some better at taking risks than others? This hour, TED speakers explore the alluring, dangerous, and calculated sides of risk. Guests include professional rock climber Alex Honnold, economist Mariana Mazzucato, psychology researcher Kashfia Rahman, structural engineer and bridge designer Ian Firth, and risk intelligence expert Dylan Evans.
Now Playing: Science for the People

#541 Wayfinding
These days when we want to know where we are or how to get where we want to go, most of us will pull out a smart phone with a built-in GPS and map app. Some of us old timers might still use an old school paper map from time to time. But we didn't always used to lean so heavily on maps and technology, and in some remote places of the world some people still navigate and wayfind their way without the aid of these tools... and in some cases do better without them. This week, host Rachelle Saunders...
Now Playing: Radiolab

Dolly Parton's America: Neon Moss
Today on Radiolab, we're bringing you the fourth episode of Jad's special series, Dolly Parton's America. In this episode, Jad goes back up the mountain to visit Dolly's actual Tennessee mountain home, where she tells stories about her first trips out of the holler. Back on the mountaintop, standing under the rain by the Little Pigeon River, the trip triggers memories of Jad's first visit to his father's childhood home, and opens the gateway to dizzying stories of music and migration. Support Radiolab today at