We’re aware that a good night’s sleep helps to restore energy, but a new study in rats and mice, carried by scientists at Cornell University, has found that sleep also resets another vital function, memory. Their research showed that at certain times during deep sleep, specific parts of the hippocampus go silent, allowing those neurons to reset.
Learning or experiencing new things activates neurons in the hippocampus, a region of the brain vital for memory. Later, during sleep, those same neurons repeat the same pattern of activity, which is how the brain consolidates those memories that are then stored in a large area called the cortex. But how is it that we can keep learning new things for a lifetime without using up all of our neurons?
The Cornell University team studied neuronal activity in various areas of the hippocampus in mice and rats during learning tasks and during sleep. They identified activity in the brain that occurs while we sleep—a barrage of action potentials, or a BARR—that plays a crucial role in rebalancing the hippocampal neural network during memory consolidation. The findings offer fresh insights into how our brains preserve memories while maintaining stability, as we slumber.
“This mechanism could allow the brain to reuse the same resources, the same neurons, for new learning the next day,” said Azahara Oliva, PhD, assistant professor of neurobiology. The researchers believe they now have the tools to boost memory, by tinkering with the mechanisms of memory consolidation, which could be applied when memory function falters, such as in Alzheimer’s disease. Importantly, they also have evidence for exploring ways to erase negative or traumatic memories, which may then help treat conditions such as post-traumatic stress disorder.
Lead author Lindsay Karsba, PhD, and corresponding author Oliva reported on their results in Science, in a paper titled “A hippocampal circuit mechanism to balance memory reactivation during sleep.”
Memory consolidation—a process that stabilizes and strengthens our recent experiences into long-term memories—occurs when we sleep. During the non-rapid eye movement (NREM) phase of sleep, hippocampal neurons display short bursts of firing activity called sharp-wave ripples (SWRs). These patterns are known to be essential for memory consolidation. “Hippocampal ensembles that represent behaviorally relevant aspects of experience are reactivated together during SWRs,” the team wrote. “Disruption or enhancement of SWRs in sleep after learning results in memory impairment or improvement, respectively.”
However, the mechanism by which the hippocampus rebalances its activity after this selective increase in firing rates has been unknown. “We hypothesized that the hippocampus leverages distinct circuit mechanisms to balance the increase in firing rates during memory consolidation,” the team continued. The hippocampus is divided into three regions: CA1, CA2 and CA3. CA1 and CA3 are involved in encoding memories related to time and space and are well-studied; less is known about CA2, which the newly reported work found generates this silencing and resetting of the hippocampus during sleep.
For their studies the researchers implanted electrodes into the hippocampi of mice, which allowed them to record neuronal activity during learning and sleep. In this way the team could observe that, during sleep, the neurons in the CA1 and CA3 areas reproduce the same neuronal patterns that developed during learning in the day. But the researchers wanted to know how the brain continues learning each day without overloading or running out of neurons.
“We realized there are other hippocampal states that happen during sleep where everything is silenced,” Oliva said. “The CA1 and CA3 regions that had been very active were suddenly quiet. It’s a reset of memory, and this state is generated by the middle region, CA2.”
Cells called pyramidal neurons are thought to be the active neurons that matter for functional purposes, such as learning. Another type of cell, called interneurons, has different subtypes. The researchers discovered that the brain has parallel circuits regulated by these two types of interneurons—one that regulates memory, the other that allows for resetting of memories.
A subset of CA2 cells fired long barrages of action potentials (BARRs) during NREM sleep. “In addition to SWRs, we observed a different type of network event wherein a subset of CA2 pyramidal cells fired long barrages of action potentials (BARRs), coincident with an increased firing in a subset of CA1 and CA2 interneurons, the team wrote. CA1 neurons that had increased their activity during learning were inhibited. “BARRs selectively inhibited task-related CA1 pyramidal cells in an activity-dependent manner,” the researchers explained. “The more reactivated a given cell was during the learning and, subsequently, during post sleep SWRs, the more it was inhibited during BARRs.”
After learning, disrupting BARRs using optogenetic manipulation led to impaired memory performance. This suggests that a balanced level of neuronal reactivation is essential for memory consolidation, and either too little or too much reactivation can lead to memory problems. BARRs appear to help maintain this balance, preventing excessive neuronal activity that could become pathological. “Our results were replicated for several types of memory tasks and different species, indicating that BARRs are a general hippocampal mechanism that contributes to memory consolidation,” the authors further noted.
The results help to explain why all animals require sleep, not only to fix memories, but also to reset the brain and keep it working during waking hours. “We show that memory is a dynamic process,” Oliva said.
In a related Perspective, Xiang Mou, PhD, and Daoyun Ji, PhD, at the University of California, Berkeley, wrote, “The discovery of BARRs reveals how hippocampal memory reactivation is delicately controlled in memory consolidation during sleep and offers a possible reconciliation between the memory reactivation theory and the synaptic downscaling theory … Future studies will likely reveal more insights into the mechanisms governing sleep-dependent memory consolidation and how they are impaired in brain disorders.”
