Scientists Discover Role of Dopamine in Mediating Short- and Long-Term Memory Dynamics

In a recent study published in NatureResearchers from Stanford University and Yale University explored the interaction between short- and long-term memory in animals.

Learning and memory in insects are controlled by a structure known as the mushroom body, analogous to the hippocampus in mammals.

While previous studies have explored this phenomenon in insects, the researchers wanted to understand how pre-existing innate responses to stimuli influence the learning of new associations and how these memories are formed and maintained over time.

Medical Xpress spoke with the study’s first author, Cheng Huang, an assistant professor at the University of Washington School of Medicine. He explains what inspired him to pursue this research: “Ever since I was a child, I have been fascinated by the vividness of our memories and how they can shape an individual’s behavior and personality.”

The researchers focused on the brain of the fruit fly. Using a combination of experimental imaging techniques and computer modeling, the researchers observed the neural activity of the fruit flies as they underwent olfactory associative conditioning experiments.

Dopamine and memory

Dopamine release has been associated with rewarding experiences, strengthening the memory of those experiences. In fact, dopamine acts as a signal that something good has happened, making it easier to remember.

This helps encode new memories and reinforce learned behaviors, thus playing a role in the formation of short- and long-term memory. It also facilitates memory storage and retrieval, thus stabilizing memories over time.

Professor Huang and his colleagues suggest that dopamine neurons in the fruit fly brain integrate information from innate responses and learned experiences with sensory stimuli.

In other words, dopamine helps process and unify the information obtained from both sources, thus influencing how the brain responds to sensory stimuli.

“Our work introduces a new understanding of the interactions between short- and long-term memory storage areas of the brain,” says Professor Huang.

“Traditional designs have focused on system consolidation, in which memories residing in short-term storage areas are transmitted during offline activity to long-term storage areas. Here, we discover a different interaction between short- and long-term memory compartments.”

Voltage imaging to study neuronal spikes

For the experimental part of the study, the researchers used 500 fruit flies, exposing them to different odors. These fruit flies were genetically modified to target specific neurons and manipulate their activity.

Some odors were paired with positive or negative stimuli (such as a reward or punishment). This tested the flies’ ability to learn and remember the association between an odor and the outcome.

Explaining why fruit fly was used, Professor Huang said: “The fruit fly brain provides an excellent model for understanding the fundamental logic and mechanisms underlying dopamine-mediated learning and memory.”

“Although it has a significantly smaller number of dopaminergic neurons compared to mammals, the Drosophila dopamine system exhibits more conserved functions in learning and memory processes.”

To measure the flies’ response to various stimuli, the researchers measured neuronal spiking activity (communication between neurons) using voltage imaging.

This method captures electrical signals by measuring voltage changes across the neuron’s membrane. When a neuron fires, a voltage change occurs that can be visualized using special sensors or dyes.

For the computational part of their work, the researchers created a model of the mushroom body circuit, constrained both by the fly’s brain wiring and by their experimental edge data, to explain and predict memory dynamics.

Gating, feedback and the role of dopamine

Researchers have discovered that dopamine neurons in the fruit fly brain encode innate and learned responses to rewards, punishments, and odors in a heterogeneous manner. These signals regulate how memories are stored and forgotten in the brain.

When short-term memories are formed, they trigger a process that opens the door to weakening certain connections between brain cells, allowing dopamine neurons to better process innate and learned signals, which in turn helps form long-term memories.

“This gate occurs via a feedback interaction, whereby signals emitted by a short-term memory unit influence activity that is entered into a long-term memory unit.”

“Once a short-term memory has been created, this feedback interaction allows a long-term memory to form rapidly upon additional presentations of the same association that led to the initial short-term memory,” Professor Huang explained.

They also found that the strength of this gate depends on a linear sum of innate and previously learned responses to sensory signals.

The computer model also revealed how dopamine mediates the interaction between short- and long-term memory. The researchers found that the timing of memory extinction training and the natural meaning of odors influence the strength and persistence of these memories.

Looking to the future

The study results reveal how different parts of the mushroom’s body work together to form short- and long-term memory.

They provide insight into the mechanisms that govern the interaction between innate and acquired information in the brain to shape behavior. In addition, they reveal the role of dopamine in mediating the interaction between short- and long-term memory.

“This mechanism could provide insights into identifying similar circuits in mammals. Ultimately, our findings could benefit the development of interventions or treatments for diseases associated with dementia in humans,” said Professor Huang.

Speaking about the impact their study could have on the field of neuroscience as a whole, Dr. Huang concluded by saying, “The biological implications of our data and modeling results are far-reaching and can provide important computational insights into the dynamic memory system and inspire new designs for learning algorithms and network architectures in artificial intelligence.”

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