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Memory and the Brain

Lee T. Robertson, Ph.D.

Abstract: This review summarizes some of the recent advances in the neurobiology of memory. Current research helps us to
understand how memories are created and, conversely, how our memories can be influenced by stress, drugs, and aging. An
understanding of how memories are encoded by the brain may also lead to new ideas about how to maximize the long-term
retention of important information. There are multiple memory systems with different functions and, in this review, we focus on
the conscious recollection of ones experience of events and facts and on memories tied to emotional responses. Memories are
also classified according to time: from short-term memory, lasting only seconds or minutes, to long-term memory, lasting months
or years. The advent of new functional neuroimaging methods provides an opportunity to gain insight into how the human brain
supports memory formation. Each memory system has a distinct anatomical organization, where different parts of the brain are
recruited during phases of memory storage. Within the brain, memory is a dynamic property of populations of neurons and their
interconnections. Memories are laid down in our brains via chemical changes at the neuron level. An understanding of the
neurobiology of memory may stimulate health educators to consider how various teaching methods conform to the process of
memory formation.
Dr. Robertson is Professor and Chair, Department of Biological Structure and Function, School of Dentistry, Oregon Health
Sciences University. Direct correspondence and reprint requests to him at the Department of Biological Structure & Function,
Oregon Health Sciences University, 611 SW Campus Drive, Portland, OR 97201-3097; 503-494-8966 phone; 503-494-8554 fax;
Key words: memory, hippocampus, amygdala, prefrontal cortex, long-term potentiation
Submitted for publication 6/7/01; accepted 9/9/01
Editors Note: This article by Robertson and the one following by Hendricson and Kleffner are presented as companion

ost people do not think much about ordinary language, can be further subdivided into
memory until they forget a name, a criti- events that are personally experienced (for example,
cal piece of information, or the place the what you had for breakfast) and memories contain-
car is parked. During such common lapses in ing factual information (for example, information
memory, the possibility of Alzheimers disease may learned in a basic science course). The implicit
jokingly come to mind. In reality, the patient with memories involve the how to aspects of our be-
Alzheimers disease illustrates how essential memory havior that include motor skills and emotional asso-
is for performing simple everyday activities, for syn- ciations with particular stimuli or events, which form
thesizing and analyzing new information, and for our likes and dislikes. Implicit memories also include
applying that information to new situations. Memory priming, which is the ability to identify an item as a
is a fundamental process of being human, since what result of previous exposure to it, even if you are un-
we remember determines largely who we are. With- aware of the previous exposurea phenomenon well
out memory, we are capable of only simple reflexes known to advertisers.
and stereotyped behaviors. There is evidence, however, that the brain does
Websters New World College Dictionary1 de- not really store whole memories, but rather stores
fines memory as what is learned and retained through pieces of information that later can be used to create
nonconscious associative mechanisms. However, memories. We often recall facts incorrectly, suggest-
neuroscientists and experimental psychologists dis- ing that memory is not simply replayed as from a
tinguish several types of memory (Figure 1), each of tape recorder. Memory can be considered a place
which is served by different combinations of brain where we store and process information, where we
regions.2,3 Two general kinds of memory are de- update existing knowledge as new information is
scribed: 1) explicit memoryconscious recollection acquired, and where we compare one experience to
of ones own previous experiences, and 2) implicit another. Different regions of the brain participate in
memorypast experiences that influence current the encoding, storage, and retrieval of particular ex-
behavior but are not consciously recalled. The ex- periences, events, facts, and skills. During retrieval
plicit memory, referred to as simply memory in of a memory, various brain areas are simultaneously

30 Journal of Dental Education Volume 66, No. 1

Techniques Used to Study
Some of the first insights into where and how
the brain processes memory came from the study of
brain-injured amnesic patients.4 Clinical observations
gave rise to the practice of creating controlled le-
sions in experimental animals, from which other
methods have evolved.5 The lesioning technique
became increasingly accurate and specific, although
experimental lesions may block circuits involved in
the acquisition or retrieval of information and not
actually affect the storage of information. After an
experimentally induced lesion, the undamaged neu-
ral tissue may also undergo various types of reorga-
nization, which can affect the interpretation of sub-
sequent behavioral studies. Consequently, researchers
have developed a number of other strategies to study
the various processes involving memory.
By recording the activity of a single neuron or
groups of neurons in animals during separate phases
Figure 1. Memory can be classified into two major
types and several subtypes. Explicit memories are of learning and memory, researchers have identified
those events and facts that can be consciously characteristic patterns of brain activity that change
recalled. Implicit memories are skills, habits, and moment by moment as the brain reacts to stimuli and
information that are acquired and retrieved uncon- executes learned responses. The synchronized actions
sciously. of networks of neurons provide insight into possible
interactions among different brain regions for vari-
activated, a process that occurs within milliseconds, ous aspects of memory storage. Recently, research-
which results in a unified memory in our conscious- ers have used isolated cells in cultures and genetic
ness. engineering to provide insights into the ability of the
In this review, we will focus on the neurobiol- brain to change its structure and chemistry in re-
ogy of explicit memories, particularly those involved sponse to environmental experiences and to reveal
in the storage of facts, and emotionally related memo- that several biochemical steps are necessary to con-
ries, such as those that might be associated with a vert short-term memories into permanent memories.
bad dental experience. After summarizing some of However, there are significant limitations to study-
the techniques used to study memory, we will ex- ing memory in animal models or in single cell prepa-
plain that explicit memories can be dissociated into rations. For example, it is difficult to know whether
short and long-lasting memories and that different animals encode personal events.
brain regions participate in the creation of explicit In the past decade, new techniques in brain
memories. We will then describe the storage of imaging of normal people while they perform learn-
memories related to emotional events. Since the same ing and memory tasks have provided an explosion
cellular processes are likely to be involved in the stor- of knowledge about the basic mechanisms of
age of both explicit and emotionally related memo- memory. These techniques, such as functional mag-
ries, we will present some of the evidence support- netic resonance imaging (fMRI) and positron emis-
ing the main hypotheses of the cellular and molecular sion tomography (PET) scans, allow researchers to
mechanisms of memory. Finally, although beyond see the brains metabolic activity and regional cere-
the scope of this review of the neurobiology of bral blood flow in specific brain regions as people
memory, we will briefly suggest a few procedures to carry out various kinds of memory tasks. The fMRI
enhance memory in our students. This topic is more and PET-based studies reveal that specific cortical
fully explored in the following companion paper by regions are active during specific tasks (such as ver-
Hendricson and Kleffner.

January 2002 Journal of Dental Education 31

bal), whereas other areas are engaged during other long-term memory. Long-term memories are for re-
types of processing (such as visuospatial). calling specific events and facts, recognition of
people and locations, and particular skills, which can
be retained for a long period, especially if revisited
Explicit Memories Can Be periodically. A unique subset of long-term memory
Dissociated into Short and Long- is remote memory that includes deeply embedded
Lasting Memories knowledge about language and music, which are of-
ten the last memories to be lost in conditions such as
Explicit memories are also classified accord- Alzheimers disease.
ing to time (Figure 2). Input from our senses is pro- An important question has been whether short-
cessed in fractions of a second and, if deemed im- term memory, working memory, and long-term
portant enough, either consciously or unconsciously, memory are simply different phases of long-term
the input is stored in short-term memory. Short-term memory or are separate or sequential phenomena.
memory is typically defined as the ability to remem- An accompanying issue has been whether single or
ber five to nine items, such as a telephone number. multiple brain structures or cellular mechanisms ac-
Like telephone numbers, short-term memories are count for all memory or, rather, the structures and
easy to lose without rehearsing. If we rehearse and cellular mechanisms change overtime. The idea that
use information, it can be kept in working memory, a different forms of explicit memory use distinct ana-
type of short-term memory, for minutes to hours. tomical circuits is supported by the existence of pa-
Depending on the extent of rehearsal or use, the tients with an impairment that prevents the forma-
memory is either discarded or planted in the tion of only some types of memory and by

Figure 2. A time-dependent process underlies the creation of different stages of memory. Short-term memory
involves retaining information or events only for seconds. Working memory involves the online processing of
information to accomplish a particular task. Long-term memory includes a relatively permanent type of memory
storage that lasts from hour to months, although some memories last a lifetime. (Modified from McGaugh JL.
Memory: a century of consolidation. Science 2000;287:248-51.)

32 Journal of Dental Education Volume 66, No. 1

experimental studies that indicate memories are ac- short-term and long-term memory and for explicit
tively transferred from one phase to the next. versus implicit memories.
The Story of HM. In 1957, Scoville and Miller4 Consolidation Hypothesis. A series of experi-
published a landmark case study of a twenty-seven- ments has been conducted to examine whether short-
year-old man (HM) with a history of epilepsy, who term and long-term memories occur sequentially or
underwent a neurosurgical procedure to bilaterally act independently, but in parallel (Figure 3). One
remove the medial temporal lobes including the hip- popular idea is that a memory is somehow consoli-
pocampus and the amygdala that lie deep within the dated from a temporary, fragile state to one that is
lobe. The surgery successfully eliminated the sei- relatively permanent.6 Many treatments can affect
zures, but immediately after the surgery, HM was short-term memory while leaving long-term memory
severely amnesic of events leading up to his opera- intact. As the example of HM demonstrated, the sur-
tion and he had a profound inability to learn and re- gical bilateral destruction of the temporal lobes in
tain any new memories of facts and events. Exten- this individual did not affect most of his presurgical
sive psychological testing revealed that HMs long-term memories. However, those brain structures
personality, perception, and intelligence did not that transfer short-term memories into long-term
change, nor did he have problems with short-term memory were compromised. A concussion, such as
memory or with learning new motor skills. However, might occur in a car accident, also typically results
HM was completely unable to form any explicit in memory loss of the events just prior to losing con-
memories after the surgery. To this day, more than sciousness. One explanation for this brief amnesia is
forty years since his surgery, HM is unable to recall that the loss of consciousness prevents the consoli-
the current date, where he lives, what he had for dation of short-term memories into long-term memo-
breakfast, or whom he may have met a few minutes ries. Evidence that time-dependent stages of memory
earlier. As HM has aged, he has even become unable are being processed independently also comes from
to recognize a current picture of himself! Since the various drugs that can disrupt either short-term or
report about HM, new models of learning and long-term memory.
memory have evolved. Models have been proposed Not all short-term memories are consolidated
for the dissociation of the neuronal substrate for into long-term storage. We clearly do not want all

Figure 3. A model of how the brain stores explicit information. The brain receives information about events and fact
(for example, a diagram or a verbal explanation) by means of its sensory systems. After the information has been
processed by the sensory association cortex, it is held in short-term or working memory. If the person is told to
specifically attend to the information, then the information may be consolidated directly from short-term memory
into long-term memory. If the person rehearses or uses the information, then the working memory can be consoli-
dated into long-term memory.

January 2002 Journal of Dental Education 33

the details of everyday experience in permanent stor- in people who had not learned it.9 The increased ac-
age, since the details would interfere with focusing tivity during sleep suggests that the brain is spend-
on what matters. Would you want to remember what ing energy to reinforce prior learning, which re-
you had for dinner last night for the rest of your life? searchers speculate might be a means by which
When consolidation is too effective, the results are memories are put into permanent storage. Although
devastating. People with superhuman memories, the molecular events underlying sleep are not fully
classified as savants,7 can recall long streams of num- known, the increases in cholinergic activity and the
bers and endless facts and words, but they have ex- decreases in the levels of serotonin that occur in vari-
treme difficulty with abstract thought. A savant might ous neuronal structures during REM are good can-
recite long sections of a novel verbatim, for example, didates for the modulation of cellular pathways.10
but have little understanding of the story.
Studies of brain activity suggest that we may
consolidate our memories of the days events while
Different Brain Regions Participate
sleeping. During sleep, the brain activity of a rat has in the Creation of Explicit Memory
a similar pattern to the activity triggered when the
Many differences exist among the various types
animal explored new environments shortly before
of memory at the systems level. Figure 4 shows some
sleeping.8 Similar results have been found for hu-
of the brain regions that are recognizably active dur-
man subjects. PET scans of human subjects during
ing short-term working memory (the prefrontal cor-
the learning of a task and then during rapid eye move-
tex and areas of the medial temporal gyrus) or in the
ment (REM) sleep (REMs are characteristic of
storage of information from short-term into long-
dreaming) revealed common brain areas that were
term (hippocampus and adjacent cortical areas of the
more active in people who had learned the task than

Figure 4. The lateral and medial views of the cerebral cortex show the locations of the prefrontal cortex that partici-
pates in working memory, the hippocampus that is important in the consolidation of short-term memories into long-
term memories, and the amygdala that takes part in the storage of memories related to emotional events. The
coronal section through the rostral part of the temporal lobe shows the relationship of the hippocampus to the
entorhinal and parahippocampal cortex that are part of the medial temporal lobe.

34 Journal of Dental Education Volume 66, No. 1

temporal lobe).11 For long-term memory, consider- rable memories. The ventromedial region of the tem-
able evidence now supports a learning and memory poral lobe also receives information already pro-
system that is different for events versus facts.2 A cessed by other cortical regions, such as the visual
separate neural structure completely supporting the or somatosensory regions. Functional neuroimaging
storage of each kind of memory probably does not (such as an fMRI) studies consistently reveal an in-
exist. It is likely that the memory critically depends crease in activity during memory of particular con-
on the joint functioning of these neural structures. cepts or facts. For example, Wagner et al.15 presented
The important question, then, is how do the various subjects with words that were later classified by the
brain areas interact? subject as remembered well, only weakly, or for-
Short-Term and Working Memory. Evidence gotten. The items remembered well were corre-
for a correlation between conscious experiences and lated with increased activity in the prefrontal cortex
sustained neural activity stems from tasks involving and the left parahippocampal-entorhinal regions.
verbal and visuospatial working memory, that is, the Comparable results were reported in subjects scanned
ability to rehearse or keep in mind such things as a as they studied pictures of everyday scenes and later
spatial location.12 While short-term memory may be tried to remember them, although the recalled pic-
used to briefly hold some information, working tures were associated with increased activity in both
memory is responsible for the short-term storage and the left and right parahippocampal region. Con-
online manipulation of information necessary for versely, neuroimaging studies in elderly people with
higher cognitive functions, such as language, plan- non-Alzheimer dementia (that is, characterized by
ning, and problem-solving. Working memory is usu- impoverished memory of facts) demonstrate a
ally divided into two types of processes: active main- neurodegenerative process within the ventromedial
tenance, which is keeping information available, and parts of the temporal lobe.16
executive control, which governs the encoding and Storage of Information from Short Term into
retrieval of information in working memory.13 Long Term. Deep within the temporal lobe are the
Distinct regions within the prefrontal lobe ap- hippocampus (from the Latin word for seahorse
pear to handle the two types of working memory, because of its arching shape) and the surrounding
with the executive control processes being handled tissue, which is collectively called the hippocampal
in anterior and ventral parts of the lobe, and the con- formation. This region somehow transfers explicit
tent-specific information (such as verbal versus information (perhaps during sleep) to permanent stor-
visuospatial) subserved by the cortex in the more age sites throughout the cerebral cortex. 17
dorsal and posterior regions. With regard to active Neuropsychologists have studied patients with dam-
maintenance, human neuroimaging studies show that age limited to the hippocampal formation and have
the prefrontal cortex is most consistently activated concluded that it is sufficient to impair only the for-
by verbal, spatial, and object information.12 mation of new long-term memories, whereas exten-
Several regions of the left prefrontal cortex sive damage of the hippocampal formation, the con-
show higher activity as the amount and complexity necting fiber bundles, and adjacent cortical tissue
of fact processing rise. Such findings have been taken can produce a complete loss of all new explicit memo-
as evidence that the left prefrontal cortex underpins ries.18 However, animal studies and recent human
the beneficial effects of semantic processing of sub- neuroimagining studies question whether the hippoc-
sequent memory.14 Support of this hypothesis was ampal formation is equally important for the memory
recently provided by Wagner et al. 15 Using of both events and facts. Neuroimaging results sug-
neuroimagining studies, Wagner showed an increase gest that human hippocampal formation subserves
in activity in the left prefrontal cortex when words the storage of events more than the storage of spe-
were categorized on the basis of semantic rather than cific facts19 and that the structure is particularly im-
physical attributes. The prefrontal neuronal activity portant during the learning of spatial or novel infor-
increases when the tasks include analysis of the mean- mationcharacterized as the binding of all
ing of the item. components of new pictorial scenes in memory.
Working memory may also involve the ventro- The hippocampal formation is described as a
medial region of the temporal lobe, which consists memory staging area that connects the multitude of
of the parahippocampal gyrus and the entorhinal stimuli associated with various events. Anatomically,
cortex (Figure 4). This region is known through le- the hippocampus consists of numerous axons form-
sion studies to be required for the formation of du- ing two-way connections among the temporal, fron-

January 2002 Journal of Dental Education 35

tal, and parietal lobes (Figure 5). The massive paral- memory.22 Because new memories build on prior
lel connections involved in laying down a memory memories, the hippocampal formation may play a
may enable us to synthesize information that involves role in the development of patterns of connections
several sensory modalities, which allows for flex- that are activated by similar pairing of sensory stimuli.
ibility in our ability to think. The hippocampus is After further repetitions of the same or similar events
able to synthesize information from multiple sensory and facts, the connections are reinforced and our
modalities and, in turn, sends connections widely to memory becomes deeply embedded in our brain.
many parts of the cerebral cortex.20 Thus, the hip- An important question raised by recent
pocampal formation is thought to play a critical role neuroimaging studies concerns the nature of the re-
in memory by relating different sensory stimuli of a lation between the hippocampus and the cortical ar-
particular event (such as place, sounds, smells, and eas of prefrontal lobe, parahippocampal cortex, and
people), binding the stimuli together, and temporarily the entorhinal cortex during the encoding of infor-
holding the information while making interconnec- mation:23 Do these regions operate serially to sup-
tions with other parts of the brain. port memory encoding, or do they act independently,
Schacter21 describes how the hippocampus may perhaps by providing separate inputs to a common
operate with the example of meeting a friend for structure such as the hippocampus? Recently,
lunch. Such an event involves the integration of vari- Fernandes and associates24 tracked the serial encod-
ous stimulithe look (the friends appearance and ing of memories within the hippocampus and the
manner), the spatial map used to travel to the restau- surrounding cortical areas (that is, the para-
rant, the feel or smell of the restaurant, and the words hippocampal gyrus and entorhinal cortex; see Fig-
on the menuinto a compendium of images and ure 1). These investigators recorded the electrical ac-
words. No one knows exactly how the hippocampal tivity with microelectrodes inserted into the brains
formation lays down memories, but the general hy- of epileptic patients in whom the hippocampus and
pothesis is that it brings together disparate, previ- the adjacent cortex were unaffected by their disease.
ously unassociated elements into a cohesive During the electrophysiological recordings, the pa-

Figure 5. Summary of possible connections between the hippocampus and possible memory storage regions. A
convergence of sensory information flows to the parahippocampal gyrus, which has reciprocal connections with the
entorhinal cortex and then the hippocampus. The hippocampus has widespread connections with multiple cortical
areas within the prefrontal cortex, and the parietal and temporal lobes.

36 Journal of Dental Education Volume 66, No. 1

tients memorized words and, after a brief distraction, related impairments in long-term memory mainly
attempted to recall them. The investigators ultimately involve the acquisition and early retrieval of new in-
found temporally staggered encoding, with the formation, and have less effect on the memory of
parahippocampal region activated before the language, visuospatial ability, and abstract reason-
hippocampus. This is consistent with the hypothesis ing.30 Neuroimaging studies also show a decrease in
that the parahippocampal cortex is an input pathway activity of the prefrontal cortex, hippocampus, and
to the hippocampus, whereas the outputs of the hip- medial temporal lobe that correlates with aging. In
pocampus and possible memory storage sites involve some cases, vascular disease or Alzheimers disease
large areas of the cerebral cortex (Figure 5). The hip- can produce marked deficits in specific types of
pocampus forms widespread reciprocal connections memory and leave other memories unaffected.
with the prefrontal lobe and large areas of the tem-
poral and parietal lobes. It has been suggested that
the hippocampus consolidates memories of facts and
concepts by its connections with the language-related
Storage of Memories Related
cortical areas. to Emotional Events
Factors That Influence Memory Storage.
Most of the changes in hormones and neurotrans- It is now generally accepted that the amygdala,
mitters that affect memory are mediated through an almond-shaped structure in the anterior part of
functional and, in some cases, structural changes in the temporal lobe (Figure 4), plays a critical role in
the prefrontal cortex, hippocampus, and medial tem- emotions and emotionally loaded memories.6,31 A
poral lobe. Those factors that negatively affect these memory may be imprinted forever as the result of a
structures would be expected to disrupt various types strong emotion, which explains why so many people
of memory. For example, interference with normal recall what they were doing, in considerable detail,
hippocampus function could impede the consolida- when President John F. Kennedy was assassinated
tion of short-term memories into long-term memo- or when the space shuttle Challenger crashed.
ries. Chronic stress, besides interfering with our sleep, During high-stress situations, information takes
can knock out molecules that transport glucose to the primary pathway through the thalamus and then
the hippocampus, suppress ongoing cell growth in the amygdala, although other brain areas are also
parts of the hippocampus, and eventually produce involved. Information then flows both ways between
neuronal damage within the hippocampus.25 Loss of the amygdala and the cerebral cortex. The amygdala
sleep and disruption of REM, caused by sleeping of the monkey, for example, processes visual infor-
pills, alcohol, or a dysfunctional thyroid gland, can mation derived from visual cortical areas where neu-
all disrupt normal hippocampal function. Chronic rons respond to the identity of faces and to facial
stress and high blood pressure can also impair work- expression. In primate social behavior, identifying
ing memory.26 and understanding the signals of facial expression
Changes in various hormones, such as estro- of another monkey are of great importance. The brain
gen, can affect memory, although the mechanisms receives the signals that the body sends during emo-
are not fully understood. During normal aging, es- tional experiences, so emotions can then influence
trogen helps maintain verbal memory in women and the subsequent behavior. Human neuroimaging stud-
may forestall the deterioration of storage of new ies reveal increases in activity within the amygdala
memories.27 It appears that estrogen exerts a specific when a person demonstrates an emotional response
effect on memory, since it enhances verbal memory to different facial expressions (for example, facial
without influencing spatial memory. One explana- signs of fear).32 We behave differently if we see an-
tion for this phenomenon is that estrogen may in- ger in a persons face than when we see a friendly
crease the level of neurotransmitters, such as acetyl- smile. Seeing anger, we might immediately withdraw
choline, which affect synaptic action. A second or avoid the person, whereas seeing a friendly smile,
hypothesis is that estrogen increases the number of we might approach or embrace the person.
synaptic contacts of hippocampal neurons.28 Although the amygdala has not been shown to
A number of hormonal and other biochemical process all types of emotions,33 convincing evidence
changes that occur during normal aging result in from animal and human studies suggests that the
subtle impairments both in accessing new informa- amygdala is strongly involved in memories associ-
tion and maintaining it in working memory.29 Age- ated with emotional arousal. Destroying, electrically

January 2002 Journal of Dental Education 37

stimulating, or inactivating the amygdala of rats im- pathways.31 While both explanations may be correct,
mediately after they receive an electric shock to the numerous animal studies and human neuroimaging
foot impairs the retention of the negative experience.34 studies support the hypothesis that emotional events
In human neuroimaging studies, the amygdala is ac- elicit specific hormones that increase the activity of
tivated by cues that connote a threat, fear condition- the amygdala, which leads to the long-term memory
ing, and the general negative effects induced by view- storage of the associated event.
ing unpleasant pictures.35,36 Although considerable The amygdala interacts with endogenous stress
evidence indicates that the amygdala is crucial for hormones, which are released as part of an emotional
memory associated with events that are intrinsically event, to modulate long-term memory storage in other
punishing, the amygdala also appears to participate parts of the brain. Injections of the adrenal medul-
in memory associated with positive emotional rein- lary hormone adrenaline enhance memory only when
forcement.37 the injections are given immediately after a learning
Two possible explanations are proposed for the experience. The effects of adrenaline on memory
way emotionally charged events are emblazoned in appear to be mediated by activation of !-adrenergic
our memories. One explanation for intense emotion- receptors of the vagal nerve, which projects to the
ally linked memories is that they are novel. People nucleus of the solitary tract located in the brainstem.
tend to discuss and, in effect, replay events in their Signals from the solitary nucleus are then relayed to
lives that are unique and/or important to them, which the amygdala.
strengthens the memory. The other explanation is that Emotional experiences are also associated with
stress hormones and neurotransmitters are released a release of hormones from the hypothalamic-pitu-
during emotional experiences, which give the event itary system. The release of both adrenocorticotro-
special significance and prominence in the memory pin and glucocorticoids can modulate memory stor-

Figure 6. A proposed neural circuit of the storage of an emotionally linked event. The event can be stored in various
brain regions, but, during a period of emotional arousal, the memory of the event can be modulated by activation of
the amygdala and emotionally activated hormones. (Reprinted from Cahill L, McGaugh JL. Mechanisms of emotional
arousal and lasting declarative memory. Trends Neurosci 1998;18:411-8. With permission of Elsevier Science.)

38 Journal of Dental Education Volume 66, No. 1

age.38 McGaugh6 and his associates have proposed pocampal neurons can be studied). These studies re-
that memories of emotionally arousing events can veal that LTP has input-specificity because enhanced
simultaneously affect the amygdala and several stress- synaptic strength occurs in only the synapses involv-
related hormonal systems, which then can also modu- ing the active pathway, whereas other synapse sites
late the activity of the amygdala (Figure 6). Since on the same cell that do not receive input are unaf-
the amygdala has widespread connections to other fected. However, LTP is also associative because the
brain areas, the amygdala can affect memory pro- activation of one set of synapses on a cell can bolster
cesses in many parts of the cortex. However, once neighboring synapses with a different input if both
the memory is stored, the amygdala is not required inputs are activated simultaneously. Producing an
for the normal retrieval of stored information or ex- effect in neighboring synapses may explain the phe-
periences, since bilateral destruction of the amygdala nomenon of associative learning, in which pairing
has no effect on an emotionally remembered event two stimuli can individually produce an identical re-
once it is stored in long-term memory. sponse. Pavlovs dogs learned to salivate when a bell
sounded whether or not food was presented.
LTP is a kind of molecular switch that initiates
a biochemical mechanism to improve synaptic effi-
Cellular and Molecular cacy. The key to LTP is the NMDA receptor (N-me-
Mechanisms Controlling thyl-D-asparate), which sits on the postsynaptic cell
membrane and binds to the neurotransmitter
Memory glutamate. The NMDA receptor is a minuscule pore
in the cells membrane that controls the entry of cal-
What happens at the cellular and molecular cium ions into the neuron. If one neuron sends sig-
level when the brain forms new memories and then nals to another neuron via the neurotransmitter
somehow translates short-term transient experiences glutamate, the NMDA receptor reacts to glutamate
into long-lasting memories that can last for days, and unleashes a cascade of chemical reactions within
weeks, or years? One popular hypothesis is that al- the postsynaptic neuron. However, the NMDA re-
ternations occur in the synapses, where neurons com- ceptor needs more than just the glutamate signal. It
municate with other neurons. The strength of the also must receive an electrical discharge from its own
connection between neurons is somehow improved cell by activating another ion channel at the same
by repeated experience. Repetition of an event, idea, time and in neighboring synapses (that is, the depo-
or fact results in the simultaneous and coordinated larization of the postsynaptic membrane causes the
activation of a pattern of neuronal connections, which removal of a Mg2+ from the pore of the NMDA re-
makes it easier for the same neuronal connections to ceptor) before the NMDA channel permits calcium
reactivate later. The change in the efficacy of the syn- ions to flow into the postsynaptic cell. This makes it
apse is considered a basic mechanism of how memory easier for the cell to turn on the next time it receives
traces are encoded.39 the same synaptic input. Thus, two separate signals,
In laboratory experiments where the ionic cur- the binding of the glutamate and the membrane de-
rents are recorded through channels of individual cells polarization, serve as coincidence detectors to help
(the patch-clamp method), the strengthening of syn- the brain associate the two events.40 Although no
aptic connections has been shown to occur when single source may be sufficient to activate the neu-
neural pathways are electrically stimulated in coor- ron, hippocampal neurons receive inputs from many
dination with other activity of neurons. This enhance- sources and, when simultaneously and repeatedly
ment in synaptic strength, which can last for hours presented (that is, temporal and spatial summation),
or even days, is known as long-term potentiation it is sufficient to activate the neuron. Synaptic plas-
(LTP), and the molecular changes that underlie LTP ticity not only occurs in the hippocampus, but in the
are the key ingredients of memory storage.39 amygdala34,41 and throughout the cerebral cortex,
Since the hippocampus is somehow involved where NMDA receptors help to establish connections
in consolidating short-term memories into long-term among various cortical inputs.39
memories, many studies have examined the synaptic The NMDA hypothesis has been tested by ei-
plasticity in a hippocampal slice preparation (where ther blocking NMDA receptors with drugs or devel-
a piece of hippocampal tissue is maintained in a cul- oping genetic strains of mice without NMDA recep-
ture dish so that the ionic currents of individual hip- tors. In both cases, the animals become

January 2002 Journal of Dental Education 39

memory-disabled. When NMDA receptor blockers term memory consolidation, thereby improving over-
are injected into the hippocampus of rats, for instance, all long-term memory retention? The first step is
they fail to learn the pattern of a maze. Likewise, the gaining the learners complete attention. Attention
genetic engineering of mice that lack a critical part filters incoming information, allowing only relevant
of the NMDA receptor in the hippocampus produces information into working memory.46 Intense atten-
mice with poor spatial memory.40 Tsien and his col- tion has a strong positive effect on tests of explicit
leagues have also tried to improve memory by stimu- memory, whereas attention has minimal value dur-
lating the NMDA receptor and, thereby, making a ing the learning of implicit memories, such as ac-
strain of mice that learn faster than their normal coun- quiring fine hand motor skills.47 Psychologists have
terparts.42,43 These researchers altered a gene in such found that retention of events and facts is increased
a way that the NMDA receptor works more effi- when students are instructed to pay particular atten-
ciently. The mice were tested with a series of stan- tion or when their attention is directed to understand-
dardized memory tasks and, compared to normal ing concepts or abstract meaning rather than con-
mice, the gene-altered smart mice were superior centrating on superficial attributes of presented
every time. Taken together, the various studies of LTP information.21
and NMDA demonstrate that these receptors appear Involving multiple sensory systems (visual,
to play an important role in synaptic efficacy and auditory, and somatosensory) in the acquisition of
memory processes. It may be possible to genetically new information will improve the retention of the
engineer an animal to perform either brilliantly or information. Memory is influenced by the sensory
poorly: it all depends on whether the brain can con- modality in which the information is presented. For
solidate a memory and whether the appropriate genes example, using a dual-mode presentationauditory
are activated to produce the proteins that consolidate information with visual illustrationsresults in im-
the memory. However, the genetic engineering to proved memory performance compared to single
make smart human beings is not ethical. Because modality formats.48 It is easier to remember the con-
NMDA receptors are found throughout the brain, tent of a lecture when interesting visual illustrations
human genetic alteration could cause unforeseen and are included, as opposed to simply listening to a ver-
unpredictable complications. Further, some scientists bal presentation. However, if only one modality is
dispute the connection between LTP and memory, used, an auditory presentation results in better
since LTP typically last only hours or, at best, days, memory than a visual presentation of same the ma-
but memories can last a lifetime.44 Ultimately, the terial. This is an indication that words are processed
LTP role in memory is also only part of the story, in a distinct manner. An excellent example of an op-
since it is not yet known how memories are repre- timal learning environment is the gross anatomy labo-
sented by ensembles of neurons.45 ratory in which learning involves vision, sounds,
smells, and touch; such multimodality experiences
result in the elaborate encoding of three-dimensional
anatomical structures in long-term memory.
Procedures to Enhance We can get facts and events into long-term
Memory within Dental memory simply by rehearsing them.49 The brain
strives to make associations. If you already have an
Education established neuronal circuit for a particular type of
information, then the hippocampus effectively stores
Major marketing opportunities exist for prod- related information alongside the previous informa-
ucts and strategies to enhance memoryfrom brain- tion. It is essential, however, to allow the brain time
boosting supplements to special diets, from memory to transfer the information from working memory
training seminars to exercise programs that ensure into long-term memory. The traditional, one-hour
an ample supply of blood to the brain, and from TV didactic lecture potentially fills working memory to
talk shows to technique books on memory improve- capacity, but allows little opportunity for the con-
ment. But for dental educators, the question is how solidation of the information into long-term memory.
we can use the information about the neurobiology Holding information in working memory is effortful,
of memory to improve classroom instruction. How attention-demanding, and prone to failure when the
can we maximize the acquisition of information into information load or other cognitive demands are
working memory, and facilitate short-term to long-

40 Journal of Dental Education Volume 66, No. 1

high.49 During the didactic lecture, there is usually
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42 Journal of Dental Education Volume 66, No. 1