Scientists discover dopamine’s role in mediating the dynamics of short-term and long-term memory

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

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

While previous studies have explored this 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, Assistant Professor at the University of Washington School of Medicine. Speaking about what led him to pursue this research, he said: “Since childhood, I have been fascinated by how vivid our memories can be and how they can shape an individual’s behavior and personality.”

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

Dopamine and memory

Dopamine release has been associated with rewarding experiences, reinforcing the memory of that experience. Basically, dopamine acts as a signal that something good has happened, making it easier to remember.

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

Prof. Huang and his colleagues propose 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 information received from the two sources, influencing the way the brain reacts to sensory stimuli.

“Our work introduces a new concept of interactions between short-term and long-term memory storage areas of the brain,” explains Prof. Huang.

“Traditional concepts focused on systems consolidation, in which memories residing in short-term storage areas are shifted during offline activity to long-term storage areas. Here, we reveal a different interplay between short-term and long-term memory compartments.”

Voltage imaging to study nerve impulse

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

Some of the odors were paired with positive or negative stimuli (such as a reward or punishment). This tests how well the flies can learn and remember the association between a smell and an outcome.

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

“Despite having a significantly smaller number of dopamine neurons compared to mammals, the Drosophila dopamine system demonstrates more conserved functions in learning and memory processes.”

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

This method captures electrical signals by measuring changes in voltage across the neuron’s membrane. When a neuron fires, there is a change in voltage, which can be imaged using special sensors or dyes.

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

Gating, feedback and the role of dopamine

The researchers found that dopamine neurons in the fruit fly brain encode innate and learned responses to rewards, punishments and odors, heterogeneously. These signals regulate how memories are stored and forgotten in the brain.

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

“This entrainment occurs through a feedback interaction, where signals emanating from a short-term memory unit influence activity entering a long-term memory unit.”

“Once a short-term memory has been formed, this feedback interaction allows a long-term memory to be rapidly formed during additional presentations of the same association that led to the initial short-term memory,” explained Prof. Huang.

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

Further, the computational model revealed how dopamine mediates the interaction between short-term and long-term memory. The researchers found that the timing of memory extinction training and the natural salience of odors affect the strength and durability of these memories.

Looking ahead

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

They provide a mechanistic understanding of how innate and learned information interact in the brain to shape behavior. Furthermore, the role of dopamine in mediating the interaction between short-term and long-term memory is also revealed.

“This mechanism may provide insight into the identification of similar circuits in mammals. Ultimately, our findings may benefit the development of interventions or treatments for dementia-related diseases in humans,” said Prof. Huang.

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

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