Your Brain: Use it or lose it
 
Making Memories: How the Brain Stores Our Experience
Brain.Com Exclusive
        
We all forget things from time to time, but for some people, amnesia is asevere problem. Take the case of E.P., a 76-year old who lost his ability to form new memories following a virus infection in his brain. Even after he had met with the researchers 40 times in a single year, he still could not recognize them, and he had no familiarity with his surroundings. Yet, when he was taken on a visit to his home town in California, E.P. was as adept as five of his former school mates at finding his way around town (1).

Patients like E.P. are rare, but they tell us a lot about how the brain creates and stores memories. While E.P. had lost the ability to form any new memories, he was able to recall very distant memories from his past. This suggests that the formation of new memories, and the long-term storage of old ones, are separate processes, happening in different parts of the brain. Apparently, the virus infection damaged an area needed for new memory formation, while leaving distant memories intact.

Brain scans on patient E.P. revealed that the herpes infection had damaged an area of his brain called the hippocampus and its most closely linked areas, including the perirhinal cortex and the entorhinal cortex. It would appear that the ability to form new memories lies here.
The first inkling of the importance of the hippocampus to memory began in 1957 with a patient known as "H.M." whose hippocampus was removed during surgery to treat epilepsy. The effect was drastic: like E.P., H.M. lost the ability to form new memories, even the death of his mother escapes him. Yet, he could still recall details of his childhood (2).

In the last few years, these relatively crude clinical observations have been backed up by brain imaging studies which reveal the hippocampus at work. Eleanor Maguire and colleagues at the Institute of Neurology in London have shown that the hippocampus literally lights-up with activity in brain scans of normal individuals who are trying to learn their way around a virtual reality environment (3).

Binding

So how does the hippocampus and its associated regions create a memory? And how does it decide exactly what will be remembered?
According to animal studies by Howard Eichenbaum and colleagues at Boston University, Massachusetts, the hippocampus works by linking together different pieces of information to form a detailed snapshot of a given moment in time.

This allows, for example, the ability to compare different types of smells and remember which one was more pleasant (4). The researchers have discovered that neurons lying next to each other in the rat hippocampus can respond to different kinds of information, such as food smells or the size and appearance of their cage.

The team believes that these neurons could contribute their respective types of information to a single memory, combining both recognition of the cage and its smells, which enables the rats to return at a later time and successfully retrieve food hidden inside the cage (5).

The decision of what information will be linked, or "bound" into a single memory is not restricted to the hippocampus. The process instead appears to be a dynamic one, involving a flow of information from many different areas of the brain.

While sensory information comes directly to the hippocampus from the brainstem, a more select version of the same information also arrives from the cortex, where it has already been analyzed to determine which features are worth remembering.

As for the binding process itself, timing is everything. Jon Lisman at Brandeis University, Massachusetts, believes that the packaging together of several different cues to create a single memory depends on precisely when those cues arrive at the hippocampus. Rat studies have shown that neurons within the hippocampus enter a rhythmic pattern of firing whenever an animal explores a new environment, as if getting ready to receive new information.

Lisman believes that if a particular set of cues enters the hippocampus "in rhythm," that is at the same point in the rhythmic firing pattern, they will be packaged together as a single memory (6).

According to Eichenbaum, the hippocampus then finds common information between different memories to build up knowledge of certain facts. The facts can then be retrieved without having to recall every memory that contributed to the knowledge. Remembering that Paris is the capital of France, for example, does not require us to remember every classroom geography lesson.

Long-term memory storage

As E.P. and H.M. have revealed, new memory formation requires the hippocampus, while long-term memory storage occurs in another part of the brain--which is believed to be the cortex. Hence the ability to recall childhood memories regardless of hippocampal damage. No one yet knows, however, whether or not the hippocampus is the initial site of memory storage.

"It may serve as a temporary storage of information, which is later transferred to the neocortex, or it may serve as a cataloguing device containing pointers to where within the neocortex the information is actually stored," says Ole Paulsen of Oxford University.

What is clear, however, is that the storage process is a very gradual one, sometimes taking many years to complete. Either this is a very slow transfer process that is taking place, or it takes time for the cortex to operate independently of its hippocampal reins. Patient E.P. illustrates this well. While his ability to recall memories of the very distant past was intact, he had difficulty remembering events from the few years immediately preceding his illness, a phenomenon known as “retrograde amnesia”.

Some researchers have just had their first peek at this process of transfer, or consolidation. Bruno Bontempi, Robert Jaffard and colleagues at the Laboratoire de Neurosciences Cognitives, Université Bordeaux I, in Talence, France, have shown that the hippocampus is especially active in mice when recalling the location of food in a maze, particularly within 5 days of initially learning its whereabouts. But 25 days later, the hippocampus is less active, and the cortex seems busier (7).

Memory formation therefore appears to be a very dynamic process involving many different parts of the brain working together over long periods of time. Identifying all the parts involved, and how they operate, is the Holy Grail of memory research.

In Part II, we'll look at the important role our emotions play in the formation of memories and the phenomenon of long-term potentiation (LTP) that neurons use to strengthen the connections they make. We’ll also look towards possible future advances in boosting learning and memory and treating some types of neurodegenerative diseases such as Alzheimer’s disease.

Sources:

(1) Teng E, Squire LR. Memory for places learned long ago is intact after hippocampal damage. Nature 1999;400:675-677.

(2) Schoville WB, Milner B. Loss of recent memory after bilateral hippocampal lesions. Journal of Neurology, Neurosurgery and Psychiatry 1957;20:11-12.

(3) Maguire E, Burgess N, Donnett J, Frackowiak, RSJ, Frith CD, O'Keefe J. Knowing where and getting there: a human navigation network. Science 1998;280:921-924.

(4) Dusek JA, Eichenbaum H. The hippocampus and memory for orderly stimulus relations. Proceedings of the National Academy of Sciences 1997;94:7109-7114.

(5) Wood ER, Dudchenko PA, Eichenbaum H. The global record of memory in hippocampal neural activity. Nature 1999;397:613-616.

(6) Lisman, J. What makes the brain’s tickers tock. Nature 1998;394:132-133.

(7) Bontempi B, Laurent-Demir C, Destrade C, Jaffard R. Time-dependent reorganisation of brain circuitry underlying long-term memory storage. Nature 1999;400:671-675.