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How Sleep Builds Relational Memory

Learning connections between unrelated items requires neurons and brain circuits representing these items to be active and interact during sleep

Sleep is required to bind and strengthen relational memories — learned connections between unrelated items, such as names and faces. (Pixabay)

Relational memory is the ability to remember arbitrary or indirect associations between objects, people or events, such as names with faces, where you left your car keys and whether you turned off the stove after cooking but before you left the house.

Previous research has established that animal and human memory benefits from sufficient, quality sleep. In a new study, published May 25, 2022 in the Journal of Neuroscience, Maxim Bazhenov, PhD, professor of medicine at University of California San Diego School of Medicine, and Timothy Tadros, a graduate student in his lab, describe the underlying mechanisms that strengthen or create new relational memories during sleep.

The authors developed an artificial model of two regions of the brain: the thalamic (involved in earlier sensory processing) and the cortical (involved in memory, learning and decision-making). The model was capable of simulating two major brain states: awake when neurons are spontaneously active and optimized to process sensory input and deep sleep when intrinsic oscillations of electrical activity are generated, such as slow-waves.

The properties of the network model could be changed to promote transitions between awake and asleep activity, similar to what the biological brain does every day.

In the cortical region, connections between the neurons were permitted to become stronger or weaker based on their activity, known as synaptic plasticity, which reflects the primary known biological mechanism for how memories are formed or erased.

“We modelled the cortex after visual processing, with one cortical layer representing primary visual cortex and another cortical layer representing associative cortex,” said Tadros. “Every time one sees the same object, roughly the same neurons in the visual cortex would be active. If a person sees two objects in the same context, then these associations might be learned in the associative cortex by strengthening connections between neurons that represent each of the two objects.”

The scientists trained the network in its awake mode to learn such direct associations, such as A+B or B+C but not A+C, then discovered that in the sleep mode, the model formed indirect associations: A+C.

“This happened because during sleep the neurons representing all three related items (A, B and C) spontaneously fired in close temporal order, a phenomenon called sleep replay, which triggered synaptic plasticity and led to formation of strong synaptic connections between all these neurons,” said Bazhenov. “Therefore, after sleep, activating any one group, such as A, activated all other related groups, such as B and C.”

While primarily conceptual, the researchers said the work has real-world implications.

“One important real-world impact of the study is in informing future studies of disease, such as schizophrenia and autism spectrum disorder,” said Bazhenov. “Studies have shown that people with these conditions perform worse on relational memory tasks and also have disrupted sleep, specifically slow-wave sleep.

“Our study suggests that focusing on improving slow-wave sleep in order to alleviate some of the cognitive symptoms associated with these conditions may be a more fruitful path forward than focusing on the cognitive symptoms exclusively.”

The authors also noted that memory function and sleep quality decline with age, but current or new technologies that augment sleep oscillations may help protect and improve memory function in older adults.

Funding for this research came, in part, from the Office of Naval Research (grant MURI: N00014-16-1-2829), the National Science Foundation (IIS-1724405) and the National Institutes of Health (1RO1MH125557 and 1RO1MH117155).


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