Imagine glimpsing a celebrity taking a selfie at the Eiffel Tower and later relaying that split-second encounter to a friend. How did your brain form a memory of that one episode? A group led by Rodrigo Quian Quiroga, University of Leicester, England, and Itzhak Fried, University of California, Los Angeles, suggest a mechanism for these instant episodic memories in the July 1 Neuron. They report that individual human brain cells alter their firing pattern in response to such fleeting encounters. The finding hints that rapid adaptation by single neurons underlies encoding of episodic memories. 

“Having a better understanding of how assemblies of neurons represent learning and memory might lead to novel ways to improve the cognitive deficits in patients with some neurological disorders,” first author Matias Ison told Alzforum.

The researchers studied patients who had temporary electrodes implanted in their brains to guide surgical procedures that would treat epileptic seizures. The electrodes can record from single neurons. Previously, Quiroga had reported on individual brain cells in the medial temporal lobe that respond to different, though related images, such as of Luke Skywalker and Yoda, characters from the “Star Wars” movies (Quiroga, 2012). He called them “concept cells,” because they encoded a common notion. Likewise, other concept cells responded to images of two researchers the patients had only just met, implying that these concept cells rapidly made associations. His group wondered how fast neurons formed these connections, and what role they might have in learning and memory.

To find out, Ison and colleagues initially screened 14 epilepsy patients, aged 18 to 53, by showing them more than 100 images and measuring their neural responses. Electrodes had been implanted in these volunteers in the medial temporal lobe, depending on where seizures were suspected to start. Regions included the hippocampus, entorhinal cortex, amygdala, and parahippocampal cortex. From the 100 or so images, the researchers chose an average of 14—half of a known celebrity and the other half of a familiar place—that specifically triggered one individual neuron in each subject.

During the experiment, patients viewed the images individually, allowing the researchers to record baseline firing for each neuron. Then the researchers combined images by superimposing one of the celebrities onto one of the places. For instance, actor Clint Eastwood might appear in front of the Leaning Tower of Pisa (see image above), or volleyball player Kerri Walsh Jennings could be pictured in front of the White House. They flipped through these composite pictures in random order about 15 times. The task was meant to mimic the kind of episodic memories created when encountering a person in a specific place.

The scientists found that individual neurons that at first were triggered only by one person or one place began to fire at the sight of the associated image, too. For example, the neuron initially triggered by the visage of Clint Eastwood began to fire at the image of the leaning tower. Interestingly, this new burst of firing began as soon as the subject “learned” the association, meaning that it occurred as soon as the patient correctly associated the face/place pair. This suggested that the new firing pattern underlay the learning. “These neurons change their behavior exactly at the moment of learning,” Ison told Alzforum. In many cases, this occurred after just one trial, implying that these firing changes can happen instantly.

“This and earlier work by the group provides a compelling picture of how individual neurons in the hippocampus and neighboring cortical areas encode memories,” said Howard Eichenbaum of Boston University. Animal studies have implied that single neurons change firing patterns as they rapidly encode associative memories, but this is the first time it has been observed in people, he told Alzforum (Wirth et al., 2003; McKenzie et al., 2013). “It fits with the growing evidence that associations are encoded when sets of neurons become activated by both elements of the association,” Eichenbaum said. Because associative memory deteriorates early in Alzheimer’s and other disorders of memory, understanding how it works will give scientists something to focus on when they look at treatments, he added.

“This group is detecting rapid learning at the level of single neurons,” said John Wixted, University of California, San Diego. He agreed with the authors that this is a hard quality to study in animals because they usually require multiple trials and copious rewards to learn an association. Wixted said the study presents good evidence that the task is picking up on episodic memory, but he would like to see it replicated in more patients and with other methodologies to be more certain.

Ison said he is interested to know what happens to these associations next, when they are either forgotten or stored in long-term memory.—Gwyneth Dickey Zakaib

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References

Paper Citations

  1. . Concept cells: the building blocks of declarative memory functions. Nat Rev Neurosci. 2012 Jul 4;13(8):587-97. PubMed.
  2. . Single neurons in the monkey hippocampus and learning of new associations. Science. 2003 Jun 6;300(5625):1578-81. PubMed.
  3. . Learning causes reorganization of neuronal firing patterns to represent related experiences within a hippocampal schema. J Neurosci. 2013 Jun 19;33(25):10243-56. PubMed.

Further Reading

Papers

  1. . Medial Prefrontal Cortex Role in Recognition Memory in Rodents. Behav Brain Res. 2015 Jun 23; PubMed.
  2. . The medial temporal lobe and recognition memory. Annu Rev Neurosci. 2007;30:123-52. PubMed.

Primary Papers

  1. . Rapid Encoding of New Memories by Individual Neurons in the Human Brain. Neuron. 2015 Jul 1;87(1):220-30. PubMed.