University of California, Irvine researchers have identified that axons within the hippocampus, not just the traditional thalamo-cortical system, are responsible for generating two critical brain waves for deep sleep.

Summary: Researchers at UC Irvine have discovered that the hippocampus, not just the thalamo-cortical circuit, generates critical brain waves for deep sleep: slow waves and sleep spindles. This finding, detailed in Scientific Reports, shows these waves originate in the hippocampus’s cornu ammonis 3 region axons, independent of neuronal spikes. Utilizing advanced techniques, the team observed these oscillations at the single-axon level, challenging previous beliefs about their generation and offering new insights into sleep’s role in memory processing that could lead to novel treatments for sleep-related disorders.

Key Takeaways: 

  • The UC Irvine study reveals that the hippocampus, specifically the axons within the cornu ammonis 3 region, is a new source of slow waves and sleep spindles, which are crucial for deep sleep. Previously, these were believed to originate solely from a brain circuit linking the thalamus and cortex.
  • The research demonstrates that these brain waves occur independently of neuronal spiking activity, which challenges the existing theories that brain waves primarily arise through volume conduction mediated by neuronal spikes.
  • The team used different techniques, including in vitro reconstructions and microfluidic tunnels, to study isolated hippocampal neurons and detect spontaneous spindle waves directly in single axons, providing a clearer understanding of the underlying mechanisms of memory consolidation during sleep.

University of California, Irvine biomedical engineering researchers have uncovered a previously unknown source of two key brain waves crucial for deep sleep: slow waves and sleep spindles. 

Traditionally believed to originate from one brain circuit linking the thalamus and cortex, the team’s findings, published in Scientific Reports, suggest that the axons in memory centers of the hippocampus play a role.

Challenging Traditional Theories

For decades, slow waves and sleep spindles have been identified as essential elements of deep sleep, measured through electroencephalography recordings on the scalp. However, the UC Irvine-led team revealed a novel source of these brain waves within the hippocampus and were able to measure them in single axons.

The study demonstrates that slow waves and sleep spindles can originate from axons within the hippocampus’ cornu ammonis 3 region. These oscillations in voltage occur independently of neuronal spiking activity, challenging existing theories about the generation of these brain waves.

“Our research sheds light on a previously unrecognized aspect of deep sleep brain activity,” says lead author Mengke Wang, former UC Irvine undergraduate student in biomedical engineering who is now a graduate student at Johns Hopkins University (Wang conducted the study while at UC Irvine), in a release. “We’ve discovered that the hippocampus, typically associated with memory formation, plays a crucial role in generating slow waves and sleep spindles, offering new insights into how these brain waves support memory processing during sleep.”

Research Techniques

The team utilized different techniques—including in vitro reconstructions of hippocampal subregions and microfluidic tunnels for single axon communication—to observe spontaneous spindle waves in isolated hippocampal neurons. These findings suggest that spindle oscillations originate from active ion channels within axons, rather than through volume conduction as previously thought.

“The discovery of spindle oscillations in single hippocampal axons opens new avenues for understanding the mechanisms underlying memory consolidation during sleep,” says co-author Gregory Brewer, PhD, adjunct professor of biomedical engineering, in a release. “These findings have significant implications for sleep research, potentially paving the way for new approaches to treating sleep-related disorders.”

Brewer’s other research affiliations include the Institute for Memory Impairment and Neurological Disorders and the Center for Neurobiology of Learning and Memory.

By uncovering the hippocampus’ role in generating slow waves and sleep spindles, the researchers say this research expands the understanding of the brain’s activity during deep sleep and its impact on memory processing and offers a foundation for future studies exploring the therapeutic potential of targeting hippocampal activity to improve sleep quality and cognitive function.

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