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Multiple memory processes following training that a food is inedible in Aplysia.

In many organisms, memory after training can be separated into a number of processes. We now report that separable memory processes are also initiated by a training procedure affecting Aplysia feeding behavior, a model system for examining the neural mechanisms underlying the regulation of a complex behavior. Four distinct memory process were identified: (1) a very short-term memory that declines within 15 min, (2) a short-term memory that persists for 0.5-1.0 hr, (3) an intermediate-term memory, observed 4 hr after training, and (4) a long-term memory that is seen only after a 12- to 24-hr delay. The four memory processes can be distinguished by the different training procedures that are required to elicit them. A single 5-min training session is sufficient to elicit the very short-term memory. However, a longer training session that continues until the animal stops responding to food is needed to elicit short-term memory. Intermediate-term memory is observed only after a spaced training procedure (three 5-min training sessions separated by 30-min intervals). A single 5-min training session that does not cause either short-term or intermediate-term memory is sufficient to induce long-term memory, indicating that short- and long-term memory are independent, parallel processes. Short- and long-term memory can also be separated by the effects of a post-training experience. Long-term, but not short-term, memory can be attenuated by cooling animals immediately after training. Cooling before the training does not affect either the training or the subsequent short- or long-term memory.

Animals↗

[Memories and Alzheimer's disease].

INTRODUCTION: Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Memory loss is generally the most pervasive cognitive symptom of AD but is not the only one and is not homogeneous in its loss. DEVELOPMENT: Memory complaint is one of the most frequent complaints in elderly people but not all complaints of memory inefficiencies in old age reflect dementing illnesses. Amnesia is the failure or lack of memory. Research in cognitive psychology and neuropsychology of memory has produced evidence than human memory is not a unitary aspect of human cognition but is organized in independent systems. Tulving (1995) and Van der Linden (1997) identified at least five major memory systems: primary memory or working memory, episodic memory, semantic memory, procedural system and perceptual priming. From a theoretical view of multiple memory systems, the purpose of the present conference is the review of multiple systems models of human memory and the memory processes, encoding, storage and retrieval in AD and memory assessment. Memory assessment is not limited by formal testing and requires ecological assessment by daily living tasks of AD patients. Appropriateness of multiple memory systems models is discussed.

Alzheimer Disease↗

The Memory Assessment Scales and lateralized temporal lobe epilepsy.

We report Memory Assessment Scales (MAS) performance in 101 patients with unilateral temporal lobe epilepsy (TLE; left, n = 51; right, n = 50) with left cerebral language dominance. A significant multivariate group effect was present for the major summary indices (Verbal Memory, Visual Memory, and Global Memory, p < .04). Univariate analyses revealed no significant differences for either the Global Memory or Verbal Memory summary scores, although a significant group difference was present for Visual Memory (p < .04). The Verbal Memory-Visual Memory discrepancy score was significantly different between right and left TLE groups (p < .004). Verbal Memory scores were at least 14 points lower than Visual Memory scores in 34 patients (left = 20, 59%; right = 14, 41%). Visual Memory scores were at least 14 points lower than Verbal Memory performance in 20 patients (left = 5, 25%; right = 15, 75%). Diagnostic efficiency statistics show higher sensitivity but lower specificity in group classification for left TLE patients. These data suggest that the MAS is sensitive to material-specific memory deficits associated with a unilateral temporal lobe seizure focus. However, over one-third of the patients (19/54) with at least a 14-point Verbal Memory-Visual Memory discrepancy were classified incorrectly. The MAS, like other material-specific memory measures, should be interpreted within the context of other clinical findings.

Adult↗

Effects of two antidepressants on memory performance in depressed outpatients: a double-blind study.

Forty outpatients with primary depression were randomly assigned on a double-blind basis to treatment with amitriptyline (a tricyclic antidepressant) or clovoxamine (a nontricyclic, experimental antidepressant). Memory and depression were assessed during a pretreatment baseline period and at the end of days 4, 7, and 28 of drug treatment. A signal detection recognition memory task and conventional memory measures (including the Benton Visual Retention, Wechsler Logical Memory, and verbal learning tests) were used to assess memory. Although both drugs led to comparable clinical improvement in depression, they affected memory performance differently. The signal detection recognition memory task detected an impairment in memory after chronic amitriptyline administration, as contrasted with an improvement in memory after chronic administration of clovoxamine. The memory impairment in the amitriptyline group and improvement in the clovoxamine group were the result of changes in sensitivity [P(A)]. No changes in response bias (B) were detected. Conventional memory tests failed to detect drug-related differences in memory between the two groups. On the Benton, errors decreased over time within both drug treatment groups, whereas correct reproductions increased within the amitriptyline group only. However, between-group differences on the Benton did not reach significance. Results from the signal detection task suggest an amitriptyline-associated memory impairment. However, this interpretation is tempered by the finding that conventional memory measures failed to detect differences in memory performance between the two groups. We discuss the limitations of traditional memory measures and the utility of a signal detection approach in studies of psychopharmacologic influences on memory.

Adult↗

Hippocampal alpha 7 and alpha 4 beta 2 nicotinic receptors and working memory.

Nicotine and other nicotinic receptor agonists have been found in a variety of studies to improve memory, while nicotinic receptor blockade can impair memory. The critical neural mechanisms for nicotinic involvement with memory are still under investigation. Initial evidence supports the involvement of the ventral hippocampus. Lesions in this area block nicotine-induced memory improvement and mecamylamine-induced impairment. Local ventral hippocampal application of the nicotinic channel blocker mecamylamine impairs memory in the 8-arm radial maze. Both alpha 4 beta 2 and alpha 7 nicotinic receptors seem to be involved. Ventral hippocampal infusions of high doses of the alpha 4 beta 2 nicotinic antagonist dihydro-beta-erythrodine (DH beta E) and the alpha 7 nicotinic antagonist methyllycaconitine (MLA) impair memory performance on the 8-arm radial maze. However, high doses of these drugs may limit specificity and they cause preconvulsant effects, which in themselves may affect memory. The current study used the more challenging 16-arm radial maze to determine the effects of lower doses of these drugs on memory and to differentiate effects on working and reference memory. Adult female Sprague-Dawley rats were trained on a working and reference memory task in the 16-arm radial maze and then were implanted with bilateral chronic guide cannulae directed to the ventral hippocampus. After recovery from surgery, the rats received acute intrahippocampal infusions of dose combinations of DH beta E and MLA. In the first study, DH beta E (0 and 6.75 microg/side) and MLA (0, 6.75, 13.5 and 27 microg/side) were administered in a counter-balanced order. In the second study, lower doses of DH beta E (0, 1.6375, 3.275 and 6.75 microg/side) were administered alone or with MLA (0 and 6.75 microg/side) in a counter-balanced order. In the first study, DH beta E caused a significant increase in both working and reference memory errors. MLA at a dose of 27 microg/side caused a significant increase in working memory errors, but this dose had no significant effect on reference memory errors. Interestingly, no additive effects were seen with combined administration of DH beta E and MLA in this study, and at the doses used, no effects were seen on response latency. In the second study, lower doses of DH beta E did not cause a significant deficit in working memory performance. Co-administration of MLA with these subthreshold doses did precipitate a memory impairment. The current results confirm the specificity of the memory deficits caused by these drugs. These results support the involvement of alpha 4 beta 2 and alpha 7 nicotinic receptors in the ventral hippocampus as being critical for memory function.

Acetylcholine↗

Memory function in normal aging.

Basic findings obtained on memory functions in normal aging are presented and discussed with respect to five separate but interacting memory systems. These systems are: episodic memory, semantic memory, short-term memory, perceptual representation system and procedural memory. All available evidence from cross-sectional research shows that there is a linear, decreasing memory performance as a function of age for episodic memory. Longitudinal studies suggest, however, that this age deficit may be an overestimation, by showing a relatively stable performance level up to middle age, followed by a sharp decline. Studies on semantic memory, short-term memory, perceptual representation system, and procedural memory show a relatively constant performance level across the adult life span, although some tasks used to assess short-term memory and procedural memory have revealed an age deficit. Disregarding the mixed results for these latter two memory systems, it can be concluded that episodic memory is unique in showing an age deficit. Episodic memory is also unique in the sense that it is the only memory system showing gender differences in performance throughout the adult life span with a significantly higher performance for women.

Adult↗

Human learning and memory.

There have been several notable recent trends in the area of learning and memory. Problems with the episodic/semantic distinction have become more apparent, and new efforts have been made (exemplar models, distributed-memory models) to represent general knowledge without assuming a separate semantic system. Less emphasis is being placed on stable, prestored prototypes and more emphasis on a flexible memory system that provides the basis for a multitude of categories or frames of reference, derived on the spot as tasks demand. There is increasing acceptance of the idea that mental models are constructed and stored in memory in addition to, rather than instead of, memorial representations that are more closely tied to perceptions. This gives rise to questions concerning the conditions that permit inferences to be drawn and mental models to be constructed, and to questions concerning the similarities and differences in the nature of the representations in memory of perceived and generated information and in their functions. There has also been a swing from interest in deliberate strategies to interest in automatic, unconscious (even mechanistic!) processes, reflecting an appreciation that certain situations (e.g. recognition, frequency judgements, savings in indirect tasks, aspects of skill acquisition, etc) seem not to depend much on the products of strategic, effortful or reflective processes. There is a lively interest in relations among memory measures and attempts to characterize memory representations and/or processes that could give rise to dissociations among measures. Whether the pattern of results reflects the operation of functional subsystems of memory and, if so, what the "modules" are is far from clear. This issue has been fueled by work with amnesics and has contributed to a revival of interaction between researchers studying learning and memory in humans and those studying learning and memory in animals. Thus, neuroscience rivals computer science as a source of interdisciplinary stimulation. Research on topics such as memory for spatial location, the relation between memory and affect, and autobiographical memory reminds us that general theories of memory based on studies of verbal materials alone are limited. Investigating how people remember complex natural events should provide us with a larger set of memory phenomena to explain and consequently insight into a wider range of memory principles or a deeper understanding of the ones we already accept (e.g. the role of repetition, encoding specificity), including their functional significance for human behavior.(ABSTRACT TRUNCATED AT 400 WORDS)

Affect↗

[Dissociation of retrograde memory impairment in a case of herpetic encephalitis].

OBJECTIVE: To report an uncommon case of memory impairment after meningoencephalitis. METHOD: Detailed description of the history, the lesions, the evolution and review of the bibliography. RESULTS: A 33 year-old man showed a loss of verbal anterograde memory and a dissociation of retrograde memory impairment after an herpetic meningo-encephalitis with lesions predominant in the left temporal lobe. The patient had impairment of verbal anterograde memory. Visual memory, procedural one were intact. He had normal performances in frontal tests. Neuropsychological assessment revealed major loss of episodic biographical memory and public events memory, but sparing of semantic biographical memory and professional knowledge. This patient who was amnesic but who had not difficulties with visual memory, procedural memory, frontal abilities and didactic memory conserved ability to work. CONCLUSION: This case report emphasize the multiplicity of the memory systems and the likely links between episodic biographical memory, semantic biographical memory, autobiographic episodic memory, public event memory and didactic memory.

Adult↗

Memory as the "whole brain work": a large-scale model based on "oscillations in super-synergy".

According to recent trends, memory depends on several brain structures working in concert across many levels of neural organization; "memory is a constant work-in progress." The proposition of a brain theory based on super-synergy in neural populations is most pertinent for the understanding of this constant work in progress. This report introduces a new model on memory basing on the processes of EEG oscillations and Brain Dynamics. This model is shaped by the following conceptual and experimental steps: 1. The machineries of super-synergy in the whole brain are responsible for formation of sensory-cognitive percepts. 2. The expression "dynamic memory" is used for memory processes that evoke relevant changes in alpha, gamma, theta and delta activities. The concerted action of distributed multiple oscillatory processes provides a major key for understanding of distributed memory. It comprehends also the phyletic memory and reflexes. 3. The evolving memory, which incorporates reciprocal actions or reverberations in the APLR alliance and during working memory processes, is especially emphasized. 4. A new model related to "hierarchy of memories as a continuum" is introduced. 5. The notions of "longer activated memory" and "persistent memory" are proposed instead of long-term memory. 6. The new analysis to recognize faces emphasizes the importance of EEG oscillations in neurophysiology and Gestalt analysis. 7. The proposed basic framework called "Memory in the Whole Brain Work" emphasizes that memory and all brain functions are inseparable and are acting as a "whole" in the whole brain. 8. The role of genetic factors is fundamental in living system settings and oscillations and accordingly in memory, according to recent publications. 9. A link from the "whole brain" to "whole body," and incorporation of vegetative and neurological system, is proposed, EEG oscillations and ultraslow oscillations being a control parameter.

Aging↗

Vasopressin fragment, AVP-(4-8), improves long-term and short-term memory in the hole board search task.

The hole board search task (HBST) measures long-term and short-term memory, operationally defined as reference memory and working memory. The HBST is an open-field spatial learning test. Previously, we have shown that desglycinamide(Arg8) vasopressin (DGAVP) modulated reference memory, working memory, spatial sequence memory, and learning in the HBST in a dose-dependent manner (Vawter MP, Van Ree JM. Effects of des-glycinamide-sup-9-(arginine-sup-8) vasopressin upon spatial memory in the hole-board search task. Psychobiology 1995; 23: 45-51). To examine the potential active site of the DGAVP molecule, the fragment of the vasopressin amino acid sequence, [pGlu4,Cyt6]AVP-(4-8) (AVP-(4-8)), was administered 1 h prior to training in the HBST. Three groups received either 0, 0.3 microgram, or 1 microgram AVP-(4-8). A repeated measures MANOVA showed the AVP-(4-8) pretreatment factor to be significant (P = 0.048) on the reference memory measure, but not the working memory or learning measures. Interactions between peptide x sessions for reference memory (P = 0.015), working memory (P = 0.003) and learning (P = 0.010) indicated differences in improvement over sessions between placebo- and peptide-treated groups. Post hoc comparisons revealed that the AVP-(4-8) fragment in a dose of 0.3 microgram increased reference memory on the fourth, fifth and sixth acquisition sessions compared with placebo or 1 microgram AVP-(4-8) pretreated groups. Working memory and errors were significantly lowered by 0.3 microgram AVP-(4-8) on the first acquisition session when compared with placebo pretreatment. Thus, AVP-(4-8) improves long-term and short-term memory scores in the HBST, similar to previous results with DGAVP. However, AVP-(4-8) appears twice as potent than DGAVP in improving long-term memory scores in the HBST. The data suggest that the memory modulating property of DGAVP is contained within the amino acid sequence of the AVP-(4-8) peptide.

Analysis of Variance↗

Memory performance in severely depressed patients treated by electroconvulsive therapy.

OBJECTIVES: Depression is accompanied by disturbed implicit (unconscious) and explicit (conscious) memory functions. The aim was the assessment of immediate and delayed verbal and visual memory functions, concentration/attention during the course of electroconvulsive therapy (ECT) treatment. METHODS: Twenty severely depressed, drug-treatment resistant, elderly patients were assessed with the Wechsler Memory Scale-Revised (WMS-R) before and at the end of the ECT series. RESULTS: Patients revealed deficits in acquisition (immediate verbal and visual memory), attention/concentration, and retrieval of information (delayed memory) before ECT. After ECT, significant improvements were observed in immediate memory but not in delayed memory. Although higher total stimulation levels (millicoulombs) (P = 0.015) were associated with improvements in immediate visual memory, we found that longer duration of convulsions (P = 0.016) as well as lower levels of stimulation at last ECT (P = 0.036) were associated with improvements in immediate verbal memory. Moreover, we found that stimulation energy (millicoulombs) in total and at last ECT was the best predictor among several clinical and ECT parameters of improved visual memory and concentration and decreased verbal and general memory. CONCLUSIONS: Prefrontal cortex-related memory processes, especially immediate memory encoding, improved after ECT, whereas long-term memory remained impaired, indicating that severely depressed patients remain cognitively inferior to normal subjects despite clinically successful treatment. This study may yield a better understanding of the time course of memory alterations in severely depressed patients receiving ECT. Improvement of immediate memory may be essential for establishing normal daily activities of life in the recovery phase of depression.

Major Depressive Disorder↗

Inhibition of hippocampal protein synthesis following recall disrupts expression of episodic-like memory in trace conditioning.

Transition of short-term to long-term memory is referred to as consolidation and the process is dependent on protein synthesis. Recently, several studies have shown that expression of consolidated memory for simple forms of learning tasks (e.g., delay conditioning, contextual fear, inhibitory avoidance) becomes vulnerable to disruption by inhibition of protein synthesis when administered shortly after recall. In the present study, we address whether recall-induced dependence on protein synthesis is a fundamental property that can be applied to a form of memory requiring attentional awareness or is specific to memories for simple forms of conditioning. Trace fear conditioning is a form of learning that requires an active memory trace to associate a conditioned stimulus (CS) with an unconditioned stimulus (US) separated by time. Our data demonstrate that whether a CS-alone recall trial in a novel context acts as an extinction or reactivation trial depends on the strength of the original memory. Inhibition of protein synthesis following the recall trial in animals receiving one trace conditioning training session (that gives rise to weak memory) resulted in enhanced CS-elicited freezing compared with vehicle control, as a result of impaired extinction memory, but had no effect on contextual memory. However, inhibition of hippocampal protein synthesis following the recall trial in animals receiving two trace conditioning training sessions (that gives rise to stronger memory) resulted in impaired retention of both trace CS-US associative and contextual memory despite that the context-US association was not directly reactivated. This provides evidence that, for a robust memory, the CS-alone recall trial results in the reactivation of an episodic-like memory, including trace CS- and contextual-memory, and that hippocampal information storage for the memory as a whole is returned to a labile state requiring de novo protein synthesis. This and other studies are consistent with the role of the hippocampus in coordinating episodic memory retrieval.

Animals↗

Is binding to nicotinic acetylcholine and dopamine receptors related to working memory in rats?

Nicotinic acetylcholine (ACh) and dopamine (DA) receptor activation has been found to be important for working memory. The regional distribution of these receptors in the brain has been well characterized. However, the relationship of the region-specific nicotinic ACh and DA binding density to memory performance has not been well assessed. In the current studies the relationship of receptor binding and memory function was examined. Receptor binding and memory performance were assessed in rats in three types of conditions: 1) chronic nicotine and mecamylamine vs. vehicle infusion; 2) lesions of the fimbria-fornix or medial basalocortical projection vs. sham lesions; and 3) 2-year-old aged rats vs. 3-month-old young adult rats. Nicotinic ACh receptors were labeled by [3H]N-methyl-carbamylcholine ([3H]MCC), D1 receptors by [3H]SCH 23390, and D2 receptors by [125I]iodosulpiride. Working memory was assessed using the radial-arm maze and T-maze delayed spatial alternation tasks. Chronic nicotine infusion substantially increased nicotinic receptor binding in a variety of brain areas and significantly improved working memory performance in the radial-arm maze. However, nicotinic receptor binding did not correlate well with memory performance. The nicotinic antagonist mecamylamine did not block nicotine-induced increased nicotinic binding, but it did block nicotine-induced memory improvement. Aged rats relative to young adults showed both a decrease in nicotinic binding and impaired memory performance. However, chronic effects of nicotine on nicotinic receptor binding and memory performance did not correlate in the aged rats. Nicotine also increased nicotinic receptor binding in the aged rats in brain areas except for the VTA, but did not improve memory performance. Lesions of the medial basalocortical projection or the fimbria-fornix did not cause significant changes in nicotinic binding in their target fields, but they did cause significant deficits in memory performance. Finally, there were no significant correlations of nicotinic binding in any brain region and memory performance. DA receptor binding was not altered by chronic nicotine or mecamylamine infusion, fimbria-fornix lesions, medial basalocortical lesions, or in aged rats. However, DA receptor binding did correlate with memory performance. There was a positive correlation of T-maze accuracy and D1 receptor binding in the frontal cortex and a negative correlation of T-maze accuracy and D1 receptor binding in the VTA and dentate gyrus. In contrast, a positive correlation was seen between radial-arm maze accuracy and D1 receptor binding in the VTA. Radial-arm maze accuracy was positively correlated with D2 receptor binding in the striatum and dentate gyrus. There are significant relationships between the extent of DA receptor binding and working memory, but relationship between nicotinic ACh receptor binding density and memory is weak.

Animals↗

On the relationship between autobiographical memory and perceptual learning.

Although the majority of research on human memory has concentrated on a person's ability to recall or recognize items as having been presented in a particular situation, the effects of memory are also revealed in a person's performance of a perceptual task. Prior experience with material can make that material more easily identified or comprehended in perceptually difficult situations. Unlike with standard retention tests, effects of prior experience on a perceptual task do not logically require that a person be aware that he or she is remembering. Indeed, amnesic patients purportedly show effects of practice in their subsequent performance of a perceptual or motor task even though they profess that they do not remember having engaged in that prior experience. The experiments that are reported were designed to explore the relationship between the more aware autobiographical form of memory that is measured by a recognition memory test and the less aware form of memory that is expressed in perceptual learning. Comparisons of effects on perceptual learning and recognition memory reveal two classes of variables. Variables such as the level of processing of words during study influenced recognition memory, although they had no effect on subsequent perceptual recognition. A study presentation of a word had as large an effect on its later perceptual recognition when recognition memory performance was very poor as it did when recognition memory performance was near perfect. In contrast, variables such as the number and the spacing of repetitions produced parallel effects on perceptual recognition and recognition memory. Following Mandler and others, it is suggested that there are two bases for recognition memory. If an item is readily perceived so that it seems to "jump out" from the page, a person is likely to judge that he or she has previously seen the item in the experimental situation. Variables that influence ease of perceptual recognition, then, can also have an effect on recognition memory, so parallel effects are found. The second basis for recognition memory involves elaboration of a word's study context and depends on such factors as level of processing during study--factors that are not important for perceptual recognition of isolated words. Comparisons of perceptual recognition and recognition memory are shown to be useful for determining how a variable has its effect. Effects of study on perceptual recognition appear to be totally due to memory for physical or graphemic information. Results reported are also relevant to theories of perceptual learning. A single presentation of an item is shown to have large and long-lasting effects on its later perceptual recognition. At least partially, effects of study on perceptual recognition depend on the same variables as do effects on more standard memory tests.

Discrimination Learning↗

Memories for emotional autobiographical events following unilateral damage to medial temporal lobe.

Abnormalities of both memory and emotion have been reported in patients with unilateral damage to the anteromedial temporal lobe, probably reflecting the functions of the amygdala and hippocampus in these processes. Emotion and memory are also known to interact: emotional experiences often leave remarkably durable autobiographical memories. To explore this interaction, and to extend prior studies to the domain of autobiographical memory, we investigated the recollection of real-life emotional events in patients with unilateral damage to the anteromedial temporal lobe. Twenty-three patients who had undergone unilateral temporal lobectomy for the treatment of epilepsy (12 left, 11 right) and 20 healthy comparison participants completed an emotional autobiographical memory test. Participants were asked to recollect their five most emotional memories from any time in their lives and then they completed a word-cued autobiographical memory task. Participants dated each memory and gave ratings on scales of pleasantness, intensity, significance, novelty, vividness and frequency of rehearsal. Left temporal lobectomy (LTL) and healthy comparison groups generated similar numbers of pleasant and unpleasant memories, whereas the right temporal lobectomy (RTL) group produced significantly fewer memories of unpleasant events (P < 0.01). When memories were further categorized according to pleasantness and intensity, the RTL group produced significantly fewer unpleasant/high intensity memories than the other groups (P < 0.01). All groups reported more memories from between the ages of 10 and 30 (the so-called autobiographical memory 'bump'). The results demonstrate a positive bias in the recollection of autobiographical memory following right-sided anteromedial temporal damage. This finding is consistent with the notion that the right, but not the left, anteromedial temporal lobe is involved in the retrieval of negatively valenced, high-intensity memories.

Adult↗

Functional neuroanatomy of remote episodic, semantic and spatial memory: a unified account based on multiple trace theory.

We review lesion and neuroimaging evidence on the role of the hippocampus, and other structures, in retention and retrieval of recent and remote memories. We examine episodic, semantic and spatial memory, and show that important distinctions exist among different types of these memories and the structures that mediate them. We argue that retention and retrieval of detailed, vivid autobiographical memories depend on the hippocampal system no matter how long ago they were acquired. Semantic memories, on the other hand, benefit from hippocampal contribution for some time before they can be retrieved independently of the hippocampus. Even semantic memories, however, can have episodic elements associated with them that continue to depend on the hippocampus. Likewise, we distinguish between experientially detailed spatial memories (akin to episodic memory) and more schematic memories (akin to semantic memory) that are sufficient for navigation but not for re-experiencing the environment in which they were acquired. Like their episodic and semantic counterparts, the former type of spatial memory is dependent on the hippocampus no matter how long ago it was acquired, whereas the latter can survive independently of the hippocampus and is represented in extra-hippocampal structures. In short, the evidence reviewed suggests strongly that the function of the hippocampus (and possibly that of related limbic structures) is to help encode, retain, and retrieve experiences, no matter how long ago the events comprising the experience occurred, and no matter whether the memories are episodic or spatial. We conclude that the evidence favours a multiple trace theory (MTT) of memory over two other models: (1) traditional consolidation models which posit that the hippocampus is a time-limited memory structure for all forms of memory; and (2) versions of cognitive map theory which posit that the hippocampus is needed for representing all forms of allocentric space in memory.

Amnesia↗

Memory and the brain.

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 one's 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.

Amygdala↗

Retrograde amnesia: neither partial nor complete hippocampal lesions in rats result in preferential sparing of remote spatial memory, even after reminding.

Many lesion experiments have provided evidence that the hippocampus plays a time-limited role in memory, consistent with the operation of a systems-level memory consolidation process during which lasting neocortical memory traces become established [see Squire, L. R., Clark, R. E., & Knowlton, B. J. (2001). Retrograde amnesia. Hippocampus 11, 50]. However, large lesions of the hippocampus at different time intervals after acquisition of a watermaze spatial reference memory task have consistently resulted in temporally ungraded retrograde amnesia [Bolhuis, J. J., Stewart, C. A., Forrest, E. M. (1994). Retrograde amnesia and memory reactivation in rats with ibotenate lesions to the hippocampus or subiculum. Quarterly Journal of Experimental Psychology 47B, 129; Mumby, D. G., Astur, R. S., Weisend, M. P., Sutherland, R. J. (1999). Retrograde amnesia and selective damage to the hippocampal formation: memory for places and object discriminations. Behavioural Brain Research 106, 97; Sutherland, R. J., Weisend, M. P., Mumby, D., Astur, R. S., Hanlon, F. M., et al. (2001). Retrograde amnesia after hippocampal damage: recent vs. remote memories in two tasks. Hippocampus 11, 27]. It is possible that spatial memories acquired during such a task remain permanently dependent on the hippocampus, that chance performance may reflect a failure to access memory traces that are initially unexpressed but still present, or that graded retrograde amnesia for spatial information might only be observed following partial hippocampal lesions. This study examined the retrograde memory impairments of rats that received either partial or complete lesions of the hippocampus either 1-2 days, or 6 weeks after training in a watermaze reference memory task. Memory retention was assessed using a novel 'reminding' procedure consisting of a series of rewarded probe trials, allowing the measurement of both free recall and memory reactivation. Rats with complete hippocampal lesions exhibited stable, temporally ungraded retrograde amnesia, and could not be reminded of the correct location. Partially lesioned rats could be reminded of a recently learned platform location, but no recovery of remote memory was observed. These results offer no support for hippocampus-dependent consolidation of allocentric spatial information, and suggest that the hippocampus can play a long-lasting role in spatial memory. The nature of this role--in the storage, retrieval, or expression of memory--is discussed.

Amnesia, Retrograde↗