Episodic Memory Formation In The Hippocampus

Michael A. Colicos, UC San Diego.

In a fascinating new study, a team of researchers based at the University of California, San Diego describe experimental findings that shed light on the neural mechanisms behind episodic memory formation in the human brain. More specifically, they found that each memory is encoded, or created, within a small fraction of distributed neurons within the hippocampus and that individual neurons are committed to a small number of memories. The study has been published in PNAS.

Episodic memory is a system that enables us to remember past events, or episodes.  This system is part of one of the two major classifications of long-term memory called declarative (or explicit) memory. The other type of memory in this division is semantic memory which is our record of facts, meanings and concepts. The first step in the formation of an episodic memory is called encoding.

It is known that the formation of episodic memories in rapid succession depends on the hippocampus, which is a region of the brain critical to learning and memory. However, what remained unknown is how neurons within the hippocampus represent specific memories. Computational models suggested that each memory was likely to be coded by a small fraction of distributed hippocampal neurons but there was no experimental evidence to back this up, and whether each individual neuron is responsible for one or multiple episodic memories remained unknown. 

In order to investigate this theory, the researchers enrolled nine epilepsy patients undergoing seizure monitoring into the study. These participants all had electrodes previously implanted into their brains that were able to record single neuron activity.

The individuals were first given a list of words to memorize and were then presented with a longer list of words that contained previously studied words (targets) and new words (foils). They were asked to discriminate between the targets and the foils, and also to indicate how well they remembered the words. The researchers found that hippocampal neurons fired much more when the participants were presented with targets when compared with foils, suggesting that these cells were representative of specific memories.

Furthermore, the researchers discovered that the targets were coded in a sparsely distributed fashion throughout the hippocampus with around 2% of cells responding to any one target and 3% of targets eliciting a strong firing response in any one neuron.

“Intuitively, one might expect to find that any neuron that responds to one item from the list would also respond to the other items from the list, but our results did not look anything like that,” said lead author John Wixted in a news-release. “The amazing thing about these counterintuitive findings is that they could not be more in line with what influential neurocomputational theorists long ago predicted must be true.”

Although 2% may sound pretty small, given the number of cells present in the hippocampus this is representative of a large number of neurons, likely several hundred thousand. Therefore the loss of a single cell would have a trivial impact on the ability to recall recent events.

The researchers will continue their work by investigating whether a similar system is at play in the formation of other types of memories, such as memories of people and places. It is hoped that understanding these mechanisms will further our knowledge of memory loss associated with aging and certain neurodegenerative diseases.

“Knowing the mechanism of memory storage and retrieval is a critical step in understanding how to better treat the dementing illnesses affecting our growing elderly population,” said senior author Peter Steinmetz. 

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