Designing a medication to enhance memory is the stuff of science fiction, and it is likely to remain in that realm for a very long time.

However, leaps and bounds are currently being made in the field of memory research.

Steadily, as neuroscientists explore deeper into the brain, the mechanisms of memory formation are becoming clearer, and the ways to enhance them are drawing ever closer.

Scientists at Columbia University Irving Medical Center in New York City, NY, are at the forefront of this research. Led by Catia M. Teixeira, Ph.D., and Zev B. Rosen, Ph.D., they focused their latest project on serotonin release in the hippocampus and its impact on memory.

The hippocampus and memory

The hippocampus has been known to play a vital role in memory for a long time. In particular, it lays down long-term memories of life experiences. A region of the hippocampus referred to as CA1 is particularly important.

For instance, a study involving individuals with damage to their CA1 region found that they had “a profound impairment in place learning.” Another study that tested similar patients found severe impairments in autobiographical and episodic memory.

According to the authors of the recent study, the strength of neuronal communication through the CA1 region seems to be linked to memory formation.

The hippocampus is heavily influenced by serotonin (among other neurotransmitters), but its exact role has remained unclear. The team involved in this study wanted to dig into this a little deeper.

To inspect serotonin’s function, they investigated mouse brains using optogenetics — a technique that allows neuroscientists to turn neurons off and on using pulses of light. By playing with the various serotonin pathways in the CA1 region of the hippocampus, they could get a better understanding of what each of them was doing.

They found that if serotonin release was increased, neuronal communication in CA1 became stronger; this had the effect of improving the mice’s spatial memory. Conversely, when serotonin release was artificially blocked, spatial memory was impaired.

This showed that serotonin release in the CA1 region could boost memory but also showed that memory formation is dependent on this pathway. Their findings are published this week in the journal Neuron.

Just knowing that serotonin is crucial for memory formation was not enough; they wanted to be more specific.

Drilling down to receptor type

There are a number of serotonin receptor types — in fact, there are seven general classes of these receptors. The team wanted to identify which specific class of serotonin receptor was involved in memory.

“First,” explains Teixeira, “we found that when serotonin is released from its endogenous pools within the hippocampus during learning, memory of the learned event is strengthened.”

“We then reasoned that by identifying a dominant involvement for one type of serotonin receptor, we could test drug treatments on memory performance.”

Catia M. Teixeira, Ph.D.

Finally, the researchers hit upon the specific serotonin receptor. As Teixeira continues, “[W]e found that systemic modulation of 5-HT4 receptor function with drugs enhanced memory formation.”

This finding backs up earlier work that also identified a role for the 5-HT4 receptor in memory. Also, a recent study conducted on healthy human volunteers found that the density of 5-HT4 receptors (how many are available to bind to serotonin) in the hippocampus predicted performance on a verbal learning test.

Because most people’s cognitive ability and memory declines with age, understanding the exact mechanisms behind memory storage and retrieval could have important implications.

If a drug could be designed that enhanced the serotonergic activity at 5-HT4 receptors in the CA1 region of the hippocampus, it could one day help people to stay mentally sharp well into old age. However, it is worth noting that this is a long way down the line.

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