Spectacular Discovery of How Memories Form and Learning Takes Place

The scientists showed patients images of a person in a context e.g. Jennifer Aniston at the Eiffel Tower, Clint Eastwood in front of the Leaning Tower of Pisa, Halle Berry at the Sidney Opera House or Tiger Woods at the White House. They found that the neuron that formerly fired for a single image e.g. Jennifer Aniston or Halle Berry, now also fired for the associated image too i.e. the Eiffel Tower or Sidney Opera House.

“The remarkable result was that the neurons changed their firing properties at the exact moment the subjects formed the new memories – the neuron initially firing to Jennifer Aniston started firing to the Eiffel Tower at the time the subject started remembering this association,” said Rodrigo Quian Quiroga, head of the Centre for Systems Neuroscience at the University of Leicester.

“Moreover, we observed these changes after just a single presentation. This is a radical departure from previous experiments in animals where changes have been observed mainly after long training sessions. This is critical to understanding the neural processes underlying real-life memory formation, as in real life we are not repeatedly exposed to an event in order to remember it – just one exposure is enough.”

The researchers from the University of Leicester and Ronald Reagan UCLA Medical Center have published their research in the peer-reviewed leading journal Neuron. The research was supported by grants from the National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health (NIH), Medical Research Council (MRC), the Human Frontiers Science Program and the Mathers Foundation.

Lead author Matias Ison, Lecturer in Bioengineering in the Department of Engineering, University of Leicester, said: “This is the first study to look at how a single neuron correlates learning of new contextual associations in the human brain. The single neuron underpinning of memory formation has previously been addressed only by animal studies, which can only offer a limited account of how single events can lead to new episodic memories.”

“We previously found that individual neurons in the human brain respond selectively to concepts that are related to each other, such as two co-stars in the same television series (e.g. Jennifer Aniston and Lisa Kudrow, Rachel and Phoebe in the TV series ‘Friends’.) In this study, we wanted to combine the high selectivity of human Medial Temporal Lobe (MTL) neurons with the exquisite speed and easiness at which humans can learn complex associations and consciously declare them. For this, we created a memory game that allowed us to “incept” new associations into the subject’s brain.”

“Given the involvement of MTL neurons in memory formation, we hypothesised that we would be able to see some changes in the firing of the neurons. But the astonishing fact was that these changes were dramatic, in the sense of neurons changed from being very silent to firing a lot, and that these changes occurred at the exact moment of learning, even after one trial. The emergence of association of concepts established after single trials, linked to rapid neural activity changes, turned out to be ideal for the creation of new episodic memories.”

“Episodic memories, like running into an old school friend at the cinema, are unique experiences that rely on the very rapid formation of associations, said Dr Ison. During our research, we had the rare opportunity to work with neurosurgical patients at UCLA Medical Center. Collaborating with an interdisciplinary team of researchers from the University of Leicester and Ronald Reagan UCLA Medical Center, we were able to record from individual neurons in the Medial Temporal Lobe (MTL), the brain’s main engine of episodic memory formation.”

“We monitored the activity of individual neurons in the human brain while presenting patients with pairs of unrelated pictures in a laptop i.e. people and places. The pictures would show, for instance, a picture of Clint Eastwood with the famous Leaning Tower of Pisa at the back. We basically found that neurons rapidly changed their firing patterns to encode new associations. In this way, a cell that was responsive to only one picture before learning (say Clint Eastwood), later started firing to an associated picture (the famous Italian Tower), while remaining silent to other pictures. But the striking fact was that these firing changes occurred at the exact moment of learning and sometimes even after one single presentation. These results tell us something important about how groups of neurons in the brain encode related concepts to store new memories.”

Dr Ison said understanding the underpinnings of episodic formation is a central problem in neuroscience because of how important memory is for our everyday life. Moreover, this type of memory is affected in patients suffering from certain neurological disorders.

The discovery that individual neurons in the Medial Temporal Lobe, the brain’s main engine for memory formation, changed their firing to encode new associations even after one single presentation provides a plausible mechanism underlying the creation of new memories. The study suggests that the experience of learning can be traced back to changes in individual neurons in the brain.

Dr Ison said: “A better understanding of how assemblies of neurons represent learning and memory might lead to novel ideas about our memory capacities and how these might deteriorate in patients suffering from certain neurological disorders.”

The work is the result of a five year study carried out in collaboration between University of Leicester and Ronald Reagan UCLA Medical Center. Dr Ison said: “I have had the opportunity to work with an amazing group of patients who volunteered to participate in our study. It was very compelling to work with them. I feel very grateful.”

“Almost a decade ago, when I obtained a PhD in Statistical Physics from the University of Buenos Aires in Argentina, I decided to join Quian Quiroga’s team at the University of Leicester to work on Neuroscience. Back then it was hard to imagine that I was going to be able to contribute to the understanding of how the brain works at such vital level. It really feels like a major achievement.”

Contacts and sources:
Matias Ison