Emily Wang9.00 Paper IIDue October 8, 2004The Consolidation of MemorySpecific AimsMemory 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. [Gleitman242] Remembering something and forming a memory involves three main parts: acquisi-tion, storage, and retrieval. Acquisition involves the initial learning process, storage involvesforming a record of the memory in the nervous system, and retrieval involves drawing thatinformation out of storage and using it to react to the environment. A memory is not storedin any one specific place in the brain—instead, it is represented by the way groups of nervecells behave in concert. [Gleitman 243] Measuring and studying memory is difficult becausefixed memory does not mean fixed behavior. [McGaugh 1351]Much of the physiological research that relates to learning has sought to discover whetheror not there is evidence of p ermanent changes in neural structure due to the creation ofmemories. Comparisons have also been made between different types of memories—it isknown 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 inthe realm of learning studies. Short-term memories are stored in the hippocampus, whilelong-term memories are independent of hippocampal activities—the exception being whenlong-term memories are reactivated. It is also known that time-dependent processes areinvolved in memory storage. Scientists have also explored what factors are necessary for1the formation and retrieval of memories. [McGaugh 1351] In this proposed study, we seekto 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 fromoutside influences.BackgroundScientists have found that the hippocampus plays an integral part in the memory-buildingprocess of mammals. [Kandel 393] In the hippocampus, the pyramidal cells are those thatare crucially involved with memory storage. One question researchers dealt with early on waswhether or not the pyramidal cells of the hippocampus functioned differently from the otherneurons 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 ofthe motor neurons in the spinal cord, which are responsible for simple movement. Hence, itis not the properties of the pyramidal cells themselves, but the properties of how they forma 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 neuronsand an exceedingly complex array of interconnections between those neurons, it is difficultto study how the neurons work in concert and how these networks of neurons are affectedby learning. Accordingly, researchers have sought to use simple r, analogous models of hip-pocampus activity to elucidate processes in the human brain. Although one might think thatsimple animal models, such as those of invertebrates, might be too remote from mammals2and humans to be of any use, in actuality, one can gain much knowledge about fundamentalprinciples of neuronal organization through the study of simple animals. Moreover, scien-tists have shown that many behavioral patterns and forms of learning are consistent acrosshumans and simple animals. [Kandel 395]The giant marine snail Aplysia californicu is one simple invertebrate that has often beenused as an experimental subject in psychological research. It was used in many early studiesof hippocampal nerve activity. Three important characteristics of its nerve cells make it afavored 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 1012central nerve cells, Aplysia has only20,000. These cells are found clustered into 10 groups, called ganglia. Each ganglion isresponsible for directing a certain type or family of behaviors. This means that the simplestbehaviors that are changed through learning may involve less than 100 cells, making it easierto observe the role individual neurons play in mediating behavior. The nerve cells of Aplysiaare also large enough to be seen by the naked eye, and distinctively colored. This meansthat many of the nerve cells can be uniquely identified. A scientist can then record froma particular cell be able to return to the same cell repeatedly for additional trials. Cellscan be easily dis sected and examined for biochemical studies, and the identified cells can beinjected with labeled compounds, antibodies, or genetic construct procedures. This meansthat one can use Aplysia to study the conveying of signals inside of individual nerve cells.[Kandel 395-396]3To b egin addressing the problem of learning by using Aplysia as a model animal, cellbiologists first define d a simple behavior that could be modified by learning and give riseto memory storage. Next, they identified the cells that made up the neural circuit of thebehavior and located the critical points that had been modified by learning. Finally, theresearchers analyzed the cellular and molecular changes that occurred in resp onse to learningand memory storage. Researchers found that Aplysia, like humans and other higher-ordercreatures, 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 lessvulnerable to being disrupted or erased than newer memories. [Mactutus 1319] This hasbeen 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 relatedto this is the effect that the level of activation of a memory has on its susceptibility to beingdisrupted. A study on learning in adult male Holtzman rats showed that old memories couldbe disrupted—that retrograde amnesia could occur—if old memories