The human brain is a powerful computer. It can receive information from the sense organs (eyes, nose, ears and skin) and process the information to create a perception for you. It can also store these perceptions as what we call memory. These memories can last a whole lifetime. That is why you can remember events that happened long ago during your childhood. The mystery was how the brain stores these memories? In what format? How does it recover these memories?
Experiments conducted on mice have now shed some light on how the brain may be storing long-term memories. Synchronously firing neurons encode strong and stable memories. This provides redundancy that enables memories to persist over time. Results from these experiments have implications for understanding how memory might be affected after brain damage, such as by strokes or Alzheimer’s disease.
Memory Formation Experiments on Mice
Researchers first implanted tiny endoscopes on to the brains of experimental mice (1). These endoscopes can image and measure neuronal activity of the brain. One of these mice was placed in an experimental track, about 5 feet long with white walls. Unique symbols marked different locations along the walls of the track. For example, a bold plus sign near the right-most end and an angled slash near the centre. Sugar water (a treat for mice) was placed at either end of the track. While the mouse explored, the researchers used the implanted endoscopes to measure the activity of specific neurons in the mouse hippocampus (the region of the brain where new memories are formed) that are known to encode for places.
Researchers observed that when mice were initially placed in the track, they were unsure of what to do and wandered left and right until they came across the sugar water. In these cases, researchers measured single neurons were activated when the mice took notice of a symbol on the wall. But over multiple experiences with the track, the mice became familiar with it and remembered the locations of the sugar. As the mice became more familiar, more and more neurons were activated in synchrony by seeing each symbol on the wall. Essentially, the mice were recognising where they were with respect to each unique symbol.
This means that the mice were developing their memory (more neurons activated synchronously) with increasing time spent in the track.
Memory Fading Experiments
To study how memories fade over time, the researchers then withheld the mice from the track for up to 20 days. Upon returning to the track after this break, mice that had formed strong memories encoded by higher numbers of neurons remembered the task quickly. Even though some neurons showed different activity, the mouse’s memory of the track was clearly identifiable when analysing the activity of large groups of neurons. In other words, using groups of neurons enables the brain to have redundancy and still recall memories even if some of the original neurons fall silent or are damaged.
Upon returning to the track after a break of 20 days, mice that had formed strong memories encoded by higher numbers of neurons remembered the track easily.
Is it the same in humans?
Memory is so fundamental to human behaviour that any impairment to it can severely impact our daily life. Loss of memory occurs as part of normal ageing. This can be a significant handicap for senior citizens. In diseases like Alzheimer’s, it has devastating consequences that can interfere with the most basic routines in life. For example, recognising relatives or remembering the way back home. This work suggests that memories might fade during ageing as they are encoded by fewer neurons. If any of these neurons fail, the memory is lost. This study also suggests that one day, designing treatments that could boost the recruitment of a higher number of neurons to encode a memory could help prevent memory loss.
It is also important to note that the experiments performed in these studies were on mice. How much it translates to human brains remains to be seen. Having said that, it is currently impossible to conduct direct experiments on human brains due to ethical and technical limitations. Therefore, mice research is the best alternative to understanding human biology today. If a drug can be made that can increase the number of neurons in mice, it might also work in human brains. However, it needs to be tested.
- 1.W. G. Gonzalez, H. Zhang, A. Harutyunyan, C. Lois, Persistence of neuronal representations through time and damage in the hippocampus. Science, 821–825 (2019).