In Funes the Memorious, Argentinian writer Jorge Luis Borges tells the story of Ireneo Funes, who, after falling from a horse and injuring his head, develops the ability to remember everything.1 Unlike the mind of Borges’ character, the human brain is much more selective, storing some, but not all, information people experience throughout their lives.
How the brain chooses what information to store intrigued György Buzsáki, a neuroscientist at New York University, for decades. In a study published in Science, Buzsáki’s team described how a pattern of brain activity known as sharp wave ripples (SWR) labeled mice’s experiences in a maze, which were later replayed in their brain when the animals slept.2 Their findings point to the waking SWR as a mechanism for selecting experiences that might later be consolidated into long-term memories.
“This paper gives some evidence that there is something important, and at least much more specific than we had seen before, about individual elements of experience being stored and then replayed later,” said Loren Frank, an investigator at the University of California, San Francisco, who was not involved in the work.
Hippocampal SWR have captured Buzsáki’s interest for over 30 years. These are bursts of electrical activity that primarily occur during sleep, but they are also seen in the awake state when the brain is resting.3 Previous work from Buzsáki’s team and others revealed a key role of sleep SWR in memory consolidation, as well as awake SWR in supporting memory in rodents.4-7 Yet, researchers did not know whether these hippocampal oscillations also helped the brain decide which experiences to store and which to eliminate.
In the new study, Buzsáki and his team recorded up to 500 neurons simultaneously while mice completed 70 runs on a maze. By analyzing the firing pattern during the trials, the team could discriminate one trial from the other since a small portion of the cells behaved differently. “It’s like swimming 70 laps in a swimming pool,” explained Buzsáki. “Each lap is the same, but not quite, because you know that you are not in the first, but you haven't finished it yet, so it’s not the 70th.”
Despite being considered the most synchronous events that occur in the mammalian brain, neurons that participate in SWR fire in sequence.8 The researchers exploited this feature to examine the role of awake SWR on the selection of events. Since awake SWR emerge when the brain is idling, the team allowed the mice to take a break from the task by providing a water reward every time they concluded a trial in the maze. When the researchers looked at the SWR that emerged during the reward, they found that the neuronal firing sequence contained in those SWR was most similar to the firing sequence seen in the last five runs of the maze.
The team next investigated the relationship between these awake SWR and the ones that occur during sleep. They discovered that the neuronal firing patterns seen during the sleep SWR resembled those observed during the awake SWR. “[Sleep SWR] are replaying mostly those events that were marked by the waking sharp waves,” said Buzsáki.
Since sleep plays an important role in memory consolidation and sleep SWR have been also implicated in that process, the researchers proposed that awake SWR function as a tagging mechanism that selects information for later replay during sleep and long-term storage.9
“These sharp ripples that occur in the hippocampus have been linked to this physiological process of selective reactivation of experiences, and only those experiences which are reactivated in sleep are the ones that are consolidated in the long term,” explained Shantanu Jadhav, a neuroscientist at Brandeis University who was not involved in the research. “But what selects them for reactivation has been unknown. This study tries to get at that.”
Despite the compelling evidence suggesting that the awake SWR tag experiences for replay during sleep, Jadhav and Frank remain curious about whether these labeled events are consolidated and turn into memories in the animal’s brain. “If they're promoting memory storage, what does that mean? What does it mean in the rest of the brain that these memories are stored and then how are they brought back up again to be used to do something?” Frank said.
While understanding how the brain learns, stores, and remembers experiences has fascinated researchers for decades, they have only started to explore these and other processes under the lenses of large neuronal populations. “We have hundreds of thousands of neurons spread out across circuits. How do they work together to create these activity patterns that lead to our memory and cognition?” said Jadhav. “That's where a lot of the mystery of the brain lies.”
- Borges JL. Ficciones. Grove Press; 1962.
- Yang W, et al. Selection of experience for memory by hippocampal sharp wave ripples. Science. 2024;383(6690):1478-1483.
- Tang W, Jadhav SP. Sharp-wave ripples as a signature of hippocampal-prefrontal reactivation for memory during sleep and waking states. Neurobiol Learn Mem. 2019;160:11-20.
- Ego-Stengel V, Wilson MA. Disruption of ripple-associated hippocampal activity during rest impairs spatial learning in the rat. Hippocampus. 2010;20(1):1-10.
- Girardeau G, et al. Selective suppression of hippocampal ripples impairs spatial memory. Nat Neurosci. 2009;12(10):1222-1223.
- Jadhav SP, et al. Awake hippocampal sharp-wave ripples support spatial memory. Science. 2012;336(6087):1454-1458.
- Fernández-Ruiz A, et al. Long-duration hippocampal sharp wave ripples improve memory. Science. 2019;364(6445):1082-1086.
- Buzsáki G. Hippocampal sharp wave-ripple: A cognitive biomarker for episodic memory and planning. Hippocampus. 2015;25(10):1073-1188.
- Diekelmann S, Born J. The memory function of sleep. Nat Rev Neurosci. 2010;11(2):114-126.
