The Consolidation of Memory

Emily Wang 9.00 Paper II

Due October 8, 2004

The Consolidation of Memory

Specific Aims

Memory is a phrase that does not describe one entity, but rather encompasses many dif- ferent processes in the brain that creates a link between the present and the past. [Gleitman 242] Remembering something and forming a memory involves three main parts: acquisi- tion, storage, and retrieval. Acquisition involves the initial learning process, storage involves forming a record of the memory in the nervous system, and retrieval involves drawing that information out of storage and using it to react to the environment. A memory is not stored in any one specific place in the brain—instead, it is represented by the way groups of nerve cells behave in concert. [Gleitman 243] Measuring and studying memory is difficult because fixed memory does not mean fixed behavior. [McGaugh 1351]

Much of the physiological research that relates to learning has sought to discover whether or not there is evidence of permanent changes in neural structure due to the creation of memories. Comparisons have also been made between different types of memories—it is known that there are short-term and long-term memories, the latter of which is more stable.

The hippocampus is the portion of the brain that has come under the most scrutiny in

the realm of learning studies. Short-term memories are stored in the hippocampus, while

long-term memories are independent of hippocampal activities—the exception being when

long-term memories are reactivated. It is also known that time-dependent processes are

involved in memory storage. Scientists have also explored what factors are necessary for

the formation and retrieval of memories. [McGaugh 1351] In this proposed study, we seek to better understand how the hippocampus regulates memory formation and also the phe- nomenon of retrograde amnesia. Retrograde amnesia refers to the process whereby old, supposedly stable memories, are reactivated such that they become prone to change from outside influences.

Background

Scientists have found that the hippocampus plays an integral part in the memory-building process of mammals. [Kandel 393] In the hippocampus, the pyramidal cells are those that are crucially involved with memory storage. One question researchers dealt with early on was whether or not the pyramidal cells of the hippocampus functioned differently from the other neurons in the brain. It was discovered that all nerve cells have similar intrinsic properties, and that the signaling capabilities of the hippocampus cells do not differ from, say, that of the motor neurons in the spinal cord, which are responsible for simple movement. Hence, it is not the properties of the pyramidal cells themselves, but the properties of how they form a network with each other, that is responsible for the hippocampus’s role in learning.

Because the hippocampus in mammalian brains has a formidable number of neurons

and an exceedingly complex array of interconnections between those neurons, it is difficult

to study how the neurons work in concert and how these networks of neurons are affected

by learning. Accordingly, researchers have sought to use simpler, analogous models of hip-

pocampus activity to elucidate processes in the human brain. Although one might think that

and humans to be of any use, in actuality, one can gain much knowledge about fundamental principles of neuronal organization through the study of simple animals. Moreover, scien- tists have shown that many behavioral patterns and forms of learning are consistent across humans and simple animals. [Kandel 395]

The giant marine snail Aplysia californicu is one simple invertebrate that has often been used as an experimental subject in psychological research. It was used in many early studies of hippocampal nerve activity. Three important characteristics of its nerve cells make it a favored subject for the neural basis of learning.

First of all, the animal’s nervous system is made up of a relatively small number of cells.

While the brains of mammals have on the order of 10

central nerve cells, Aplysia has only 20,000. These cells are found clustered into 10 groups, called ganglia. Each ganglion is responsible for directing a certain type or family of behaviors. This means that the simplest behaviors that are changed through learning may involve less than 100 cells, making it easier to observe the role individual neurons play in mediating behavior. The nerve cells of Aplysia are also large enough to be seen by the naked eye, and distinctively colored. This means that many of the nerve cells can be uniquely identified. A scientist can then record from a particular cell be able to return to the same cell repeatedly for additional trials. Cells can be easily dissected and examined for biochemical studies, and the identified cells can be injected with labeled compounds, antibodies, or genetic construct procedures. This means that one can use Aplysia to study the conveying of signals inside of individual nerve cells.

[Kandel 395-396]

To begin addressing the problem of learning by using Aplysia as a model animal, cell biologists first defined a simple behavior that could be modified by learning and give rise to memory storage. Next, they identified the cells that made up the neural circuit of the behavior and located the critical points that had been modified by learning. Finally, the researchers analyzed the cellular and molecular changes that occurred in response to learning and memory storage. Researchers found that Aplysia, like humans and other higher-order creatures, also form memories of different duration and require repetition to learn things, thus showing that studies of simpler animals still have results that are pertinent to humans.

Other studies have shown that older memories in the brain are more stable and less vulnerable to being disrupted or erased than newer memories. [Mactutus 1319] This has been known since Ribot studied human amnesia and formulated the “law of regression”.

This law has been verified by many animal studies. This is due to the fact that initially- formed memories are dependent on the hippocampus Another phenomenon that is related to this is the effect that the level of activation of a memory has on its susceptibility to being disrupted. A study on learning in adult male Holtzman rats showed that old memories could be disrupted—that retrograde amnesia could occur—if old memories were first brought back to a more active state.

In this particular study, rats were taught to avoid a black half of a black-white passive-

avoidance chamber by applying shock to their feet when they entered the side that had

been painted black. After they had learned not to “fear” the black compartment, they were

removed from the chamber and returned to a home environment for 24 hours. After this

time period, 1/4 of the rats were simply treated as a control group and handled in the lab environment, while 3/4 of the rats were given a brief exposure to the black chamber that “reminded” them of the danger. Out of these rats, one-third were also submerged in cold water to a severe degree, while one-third were submerged to a milder degree. The last third were not cooled at all. After these varying treatments, the rats were all given another passive-avoidance test to see if and to what extent they had retained their prior knowledge of the black box’s danger. [Mactutus 1319]

It was observed that the rats that had merely been handled showed learning retention rates comparable to those who were only given cues. Those that had been given the cooling treatment showed substantial amounts of memory loss, however, showing that the long-term memories which had been activated had somehow become vulnerable to being disrupted.

[Mactutus 1320]

Later studies focused on the actual cellular processes that cause memories to become

long-term memories and processes that cause long-term memories to be reactivated and

become unstable again. Consolidation theory postulates that new memories require that new

proteins be synthesized in order to be stored in the brain. This was tested in a study where

the protein synthesis inhibitor anisomycin was injected into the hippocampus. It was found

that this caused amnesia for both hippocampal-dependent memories and for hippocampal-

independent memories that had been reactivated. The reactivated memories were found to

stay dependent on the hippocampus for only 2 days after reactivation, however, rather than

for weeks, as in the case of newly forming memories. [Debiec 527]

Researchers in this study also investigated whether or not there was a temporally- dependent retrograde amnesic gradient—that is, whether or not newer memories were more readily disrupted. It was found that when a hippocampus-independent memory was reacti- vated for the second time, it remained hippocampus dependent for less than 2 days. From these results, researchers postulated that each repeated use of a memory may cause the brain to go through another iteration. In effect, the brain is trying to reinforce the memory. This causes the neural networks to become malleable again, and hence the original memories can be altered or erased. An alternate interpretation of the results is that each “reactivation”

is actually the formation of a new memory trace in the brains of the subjects, and it is the new trace that is being destroyed. [Debiec 534]

Research

We seek to study the phenomenon of memory reconsolidation in the hippocampus. The specific question we seek to answer is whether or not reconsolidation in the hippocampus is involved in the creation of false memories. We hypothesize that the hippocampus is indeed involved, and we propose using two groups of human subjects: one group with normal hip- pocampus functionality and another with impaired hippocampus functionality—amnesiacs, for instance.

Subjects will first be asked if they remember a certain childhood event, such as learning

how to ride a bike. After talking to the subject’s family members to independently verify

that the account of the incident is accurate, one of the subject’s family members will then

ask the subject if he or she remembers falling and scraping a knee, even though this has never actually occurred. If it is indeed the hippocampus that is involved in the creation of false memories, then only those subjects with functioning hippocampuses should react to the suggestions and form false memories. If not, then both amnesiac subjects and non-amnesiac subjects should react similarly to suggestions that attempt to alter old, long-term memories.

The independent variable in this study would be whether or not subjects have a normal hippocampus in order to trigger old memories to become unstable. The dependent variable would be how the subjects react to suggestions that seek to alter their old, stable memories.

Confounds might be the degree to which the subjects trust the family members who provide suggestions, the degree to which the subjects trust their own memories, and also how likely it is for a subject to remember a childhood incident. These confounds could be dealt with by sampling over a large and a wide range of people.

Bibliography

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Kandel, Eric R. The Molecular Biology of Memory Storage: A Dialog Between Genes and Synapses. Nobel Lecture, Decembe r 8, (2000).

Mactutus, Charles F., David C. Riccio, and Jacquelyn M. Ferek. Retrograde Amnesia for Old (Reactivated) Memory: Some Anomalous Characteristics. Science, vol. 204, pp1319- 1320 (1979).

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