In Determining Disgust vs. Attraction, Timing is Everything

The Context: To survive, animals learn from their surroundings. Forming associations with sights, sounds, and smells helps create a bank of information and behaviors that can be used to obtain rewards and avoid threats.

The Study: What determines whether a certain stimulant, such as an odor, is processed as attractive or repulsive depends on when it is presented, finds a new study in Cell from NYSCF – Robertson Investigator Alumna Dr. Vanessa Ruta of The Rockefeller University. The research, conducted in fruit flies, also discovers that these associations are not set in stone and can be amended as flies take in new information.

The Importance: This study sheds light on the process of reward learning and identifies the cells that make it possible.


When a rabbit hears the oncoming footsteps of a predator, it knows to scurry back into its burrow. When a grizzly bear smells an elk carcass, it knows that dinner is served. To survive, animals learn from experience, picking up on which cues (such as smells, sounds, and sights) mean danger is afoot and which mean a reward is coming. But how does this process work for cues that follow an experience rather than precede it?

The Study

A new study in Cell from NYSCF – Robertson Investigator Alumna and Associate Professor of Neurophysiology and Behavior Vanessa Ruta, PhD, of The Rockefeller University explores how flies process an odor presented either before or after a reward, and finds that timing makes a big difference.

Dr. Ruta’s team delivered the “reward” via optogenetics— a tool that can precisely stimulate the brain cells that would typically activate when flies encounter something positive. When the flies were exposed to a typically neutral odor before receiving the reward, they learned to find the smell attractive. But when the same smell was presented after the reward, the flies began to avoid it.

Inside a Fly’s Brain

The root of this process takes place in a brain region called the mushroom body and involves an intricate dance between 3 types of cells: Kenyon neurons (which carry odor signals), dopamine neurons (which indicate pleasure), and output neurons (which control the flies’ behavior).

Kenyon neurons form connections with output neurons, and this relationship is tuned by the dopamine neurons. Weak connections mean the animal will find the odor attractive, strong connections mean they will avoid it.

“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 Dr. Ruta. “And we believe this is the mechanism by which the brain figures out the sequence of events.”

The Power of Flexibility

Importantly, these connections are malleable. A fly who smells a certain odor before a reward will learn to find that odor attractive— but start presenting the odor after a reward and the same fly will quickly change its mind.

This is especially critical from a survival standpoint: animals need to remain mentally flexible to adapt to an ever-changing environment. It’s important for flies, and it’s important for humans too.

“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.”

Journal Citation:

Distinct Dopamine Receptor Pathways Underlie the Temporal Sensitivity of Associative Learning
Handler A, Graham TGW, Cohn R, Morantte I, Siliciano AF, Zeng J, Li Y, Ruta V. Cell. 2019. doi: 10.1016/j.cell.2019.05.040.

Diseases & Conditions:

Neurobiology

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