Dopaminergic neurons play role in short-term memory: Mouse study
Finding challenges traditional understanding of these nerve cells' function
Dopamine-producing nerve cells, or dopaminergic neurons, in the midbrain may play a role in the temporary storage of information in short-term memory, according to new data from a mouse study.
This finding challenges the traditional understanding of these nerve cells, which were previously thought to function primarily in reward processing and movement control.
Although the study was conducted in healthy mice, the researchers say these results could have important implications for better understanding the underlying mechanisms of neurodegenerative disorders like Parkinson’s disease, in which the death of dopaminergic neurons is a hallmark feature.
“In Parkinson’s disease, midbrain dopamine neurons die off, which causes problems with movement. … But the condition can also affect higher cognitive functions, which may be related to the death of midbrain dopamine neurons,” Shigeyoshi Fujisawa, PhD, of the RIKEN Center for Brain Science, a research institution in Japan, said in a news story about the findings.
The study, “Memory-specific encoding activities of the ventral tegmental area dopamine and GABA neurons,” was published in the journal eLife.
Memory-guided maze used to test dopaminergic neurons in mice
Parkinson’s occurs when dopaminergic neurons gradually stop functioning and die. In addition to its role in movement, dopamine controls reward and higher cognitive functions like making decisions and updating short-term memory.
As a result, people with Parkinson’s experience not only the well-known motor symptoms of tremor, slowness of movement, and stiffness, but also a range of nonmotor symptoms, which may include challenges with memory, decision-making, and recognizing emotions.
“The higher cognitive functions of humans are one of the most mysterious areas of neuroscience,” Fujisawa said. “In particular, how neural networks support higher cognitive functions is a very intriguing question. I’m interested in clarifying these mechanisms.”
For example, dopaminergic neurons in the midbrain’s ventral tegmental area are known to be involved in short-term memory — the capacity to store a small amount of information and keep it available for a brief period of time. However, their responses were thought to be too slow to actually hold this type of information.
To know more, Fujisawa’s team turned to optogenetics, a technique that allows specific neurons to be switched on and off using light. The researchers then recorded the activity of those neurons in mice performing a memory-guided T-maze task.
“What the midbrain dopamine neurons encode during [short-term] working memory was unknown,” Fujisawa said. “That is why we were interested in discovering how dopamine is involved in memory encoding during a working-memory task.”
Midbrain, and not just prefrontal cortex, involved in short-term memory
The mice were placed on a T-maze, essentially a three-arm maze in the shape of the letter T, and trained to associate a visual cue with a reward in one arm of the maze. The cue appeared at some distance before the T-intersection, requiring the mice to remember it to choose the correct arm.
Some dopaminergic neurons in the ventral tegmental area fired differently when the mice were deciding to turn left or right during a memory delay, or the time between the visual cue and the decision to choose the left or right arm. The different patterns depended on memory-based decisions and not on a history of reward or running speed.
“This type of neuronal computation is supposed to occur in the prefrontal cortex, but we found that the midbrain is also involved,” Fujisawa said.
This evidence indicates that populations of [neurons] … in [a midbrain region] encode internally generated signals that support short-term memory in decision-making.
Placing the visual cue farther from the T-intersection reduced the proportion of correct choices made by the mice, which, according to the researchers, “highlights the important role of memory in supporting decisions in the present task.”
Further, the team noted that “trajectory-specific responses in the delay period of the memory task could reflect short-term memory representations linked to decision-making behavior.”
The results “cannot be explained by running speed, motor, and motivation-related signaling differences,” they wrote.
“This evidence indicates that populations of [neurons] … in the [ventral tegmental area] encode internally generated signals that support short-term memory in decision-making,” the researchers concluded.
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