Building upon previous understandings that a single memory exists as a network of neurons across various regions of the brain, researchers in Japan shed light for the first time on the integration pattern of a memory by showing that elements of a given experience instantly tied to preconfigured neuronal ensembles in various brain regions are inter-regionally integrated during post-experience sleep to form a new memory.
In the brain, neuronal ensembles that bear the memory of an experience existed beforehand, suggesting a paradox that we already know what we are about to know. New research on the integration of information on a single memory distributed throughout the brain provides a possible explanation.
In a fear conditioning task, researchers found in rats that groups of neuronal ensembles that participate in memory acquisition were configured in the amygdala and prefrontal cortex prior to memory acquisition but developed through experience in the hippocampus. “This means an ensemble’s meaning is determined later when it is connected to other ensembles through experience,” states Research Associate Hiroyuki Miyawaki, first author of the study.
Together with Professor Kenji Mizuseki of the Department of Physiology, Osaka City University Graduate School of Medicine, the two-researcher team wanted to combine two conflicting depictions of memory information. “On the one hand we know that the neuronal ensemble corresponding to a given memory is active during both acquisition and recall of the memory,” explains Professor Mizuseki, “however it is also believed that information is first stored in the hippocampus, among other areas, as short-term memory, then transferred to the cerebral cortex among other areas during sleep as long-term memory.”
The researchers saw that these differing accounts of memory information were obtained depending on the anatomical scale of interest. They concluded that a reconciliation would require they record the activity of many neurons from multiple brain regions while simultaneously analyzing the ensemble activity in the local and interregional brain network – a technically difficult task.
To overcome this, the team captured the activity of many neurons by simultaneously deploying large-scale electrophysiological recordings in the amygdala, hippocampus, and prefrontal cortex of freely behaving rats – brain regions known to house the neuronal ensembles behind memory acquisition. Next, in each brain region they mathematically analyzed the neural firing patterns during rat performance of fear conditioning tasks to identify the ensembles involved in memory and estimated the activity intensity of each ensemble. Lastly, they analyzed the temporal structure that exists between ensembles across brain regions.
There were three main findings.
First, they found that while there was synchronized activity with amygdala-prefrontal and hippocampal-prefrontal ensembles in memory acquisition, their temporal evolution was different. Amygdala-prefrontal synchrony was already present and hippocampal-prefrontal synchrony was only weakly present during memory acquisition, while both pairs showed significant activity during post-memory acquisition sleep. “When we compared the proportion of ensemble pairs showing significant activity during memory acquisition and recall,” Miyawaki explains, “the amygdala-prefrontal ensemble showed a decreasing trend while the hippocampal-prefrontal ensemble showed an increasing trend in activity.” These results suggest that the amygdala-prefrontal network forms rapidly during experience, whereas the hippocampal-prefrontal network develops relatively slow after experience.
Second, the team found that during post-memory acquisition sleep and memory recall, ensemble synchrony across the brain regions was particularly strong during transient bursts of activity such as hippocampal ripple oscillations, amygdala high-frequency oscillations, and prefrontal cortical ripple oscillations. This aligns with previous studies indicating transient burst activity is associated with memory consolidation during sleep and memory recall during wakefulness and suggests that the synchronous activity of neuronal ensembles across brain regions may also be involved.
Third, they found that the ensemble itself is present in local neuron circuits of the amygdala and prefrontal cortex before memory acquisition, while it appears in the hippocampus in an experience-dependent manner. Combined with the fact that the synchronized activity of the cross-regional ensemble is not seen prior to memory acquisition, this suggests that information about new experiences is rapidly acquired by linking it to patterns already present in the amygdala and prefrontal cortex, whereas the cross-regional network that integrates this information is formed more slowly as it relies first on the experience.
“Our findings suggest that information about new experiences is retained by being tied to pre-existing activity patterns, and that a memory is acquired when these patterns are connected to each other across brain regions via transient bursts of activity,” concludes Professor Mizuseki.
The fear conditioning task used in the study is an animal model of human post-traumatic stress disorder (PTSD). The research team hopes the result of this study can serve as a basis for the development of more effective treatments for PTSD. They also hope to expand the scope of the study beyond fear conditioning tasks to understand the operating principles of the memory system in general and elucidate issues with memory dysfunction associated with aging and disease.
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About Osaka Metropolitan University
Osaka Metropolitan University is a new public general university formed by a merger between Osaka City University and Osaka Prefecture University and established in April 2022.
With 12 undergraduate and more than 15 graduate schools, Osaka Metropolitan University offers diverse and unique curricula designed to foster students’ abilities to handle a wide range of issues.
