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Behavioral and pharmacological unravelling of memory formation.

A brief description of how a passive avoidance task, using one day-old chicks, has been used to test for memory formation is given. Chicks will peck at bright shiny beads but if a bead is painted with a bitter tasting chemical, after tasting it once, the chicks will refuse to peck on subsequent presentation of that bead. The chick associates the bitter taste with the particular characteristics of the bead. These experiments have led to the development of a model of memory. The basic model is made of short-term memory, which lasts 10 minutes, intermediate memory that has two phases A and B and lasts for 30 minutes and finally long-term memory. The use of certain classes of drugs to prolong, delay or abolish the various phases is described and then it is shown that many hormones and certain behavioral manipulations can modulate memory. Experiments are described which examine not only the temporal storage but delineate spatial storage within the brain. A brief discussion of current methodologies for looking at the exact spatial location of memory traces is given. The article concludes by emphasizing how even minor differences in protocols across laboratories can have large effects on the memory traces and stresses the significance of the narrow temporal windows, around the training trial, when memory can be modulated.

Animals↗

Wakeful response to command indicates memory potential during emergence from general anesthesia.

OBJECTIVE: An important aspect of assessing anesthetic depth is determining whether a patient will remember events during surgery. We looked for a clinical sign that would indicate a patient's potential for memory formation during emergence from anesthesia. A clinical sign indicating memory potential could be a useful endpoint for measuring the performance of anesthetic depth monitors and for titrating administration of anesthetic agents. METHODS: We evaluated patients' responses to commands to open the eyes, squeeze the hand four times, and count 20 numbers. These responses were correlated with results on recall, cued recall, and multiple-choice memory tests. MAIN RESULTS: Patients did not have evidence of memory formation until they sustained wakefulness sufficiently long to complete at least four hand squeezes or count four numbers. Of 28 patients, 13 (46%) with this sustained wakeful response had memory. Of 22 patients, 0 (0%) had evidence of memory formation when they demonstrated a brief wakeful response, defined as being responsive to command but unable to complete more than one hand squeeze or count, or an intermediate response, defined as two or three hand squeezes or counts. CONCLUSIONS: We conclude that a brief wakeful response to command indicates that a patient is unlikely to form memories, while a sustained wakeful response indicates that a patient may form memories. Thus, a patient's wakeful response to command could be a useful indicator of potential for memory.

Adult↗

Influence of other-beliefs on self-beliefs and on everyday memory self-report in the elderly.

BACKGROUND AND AIMS: Elderly people tend to evaluate their memory functioning pessimistically and have a decrease in self-efficacy beliefs associated with an attributional style which relies mainly on uncontrollable causes. This pattern may be significantly influenced by the caregivers evaluations of self-efficacy beliefs and attributional style of the elderly. This study compares older and younger adults with respect to everyday memory self-assessment, self-efficacy beliefs and attributional style, and examines the relationships between everyday memory self-assessment, self-evaluations, and evaluations by significant others as regards elderly self-efficacy beliefs, attributional style, and everyday memory. METHODS: 100 older, 100 younger, and 100 middle-aged adults were required to complete questionnaires aimed at assessing everyday memory, attributional style, and self-efficacy beliefs. The group of middle-aged adults was asked to complete questionnaires aimed at assessing the perceived efficacy and attributional style of the older and younger participants. RESULTS: Data indicate that, unlike younger adults, the elderly negatively evaluate their everyday memory, have an attributional style mainly characterized by uncontrollable factors, and have less confidence in their memory. A structural equation model shows that the opinions of the significant others (relatives or medical staff) as regards the perceived efficacy and attributional style of elderly people affect their self-efficacy and attributional style which, in turn, influence everyday self-reported memory efficiency. CONCLUSIONS: Results indicate the central role of metamemory in everyday memory evaluation in the elderly, and stress the importance of what significant others think as regards the elderly person in question. From a practical point of view, it makes an important contribution to intervention and prevention programs involving people in close contact with the elderly, by suggesting ways in which significant others can help in optimizing the ability of older people to meet the challenges of aging successfully.

Adolescent↗

Working memory in aging: maintenance and suppression.

The present research is focused on a fine-grained analysis of memory decline with aging, and the role of suppression mechanisms in age-related memory decline. Three groups of participants (continuous age ranges; young-old: 55-65 years, old: 66-75 years, and old-old: more than 75 years) were administered Forward and Backward span test, and a Working Memory task with Categorization (WMC). This new task requires lists of five words to be processed in order to individuate animal nouns, and that the last word of each list be contemporarily maintained. The words incorrectly recalled as target items, but presented during the task (intrusion errors), were computed in order to analyze the efficiency of suppression mechanisms. The findings indicated a continuous decline in working memory measures, and an early decline in short-term memory (passive storage) measures (between 60's and 70's). An age-related increase in intrusion errors was observed; the intrusion index was inversely related to working memory performance but, according to the hypotheses, was not related to short-term memory measures. These results suggest that the stronger working memory effect observed through age might be due to the combined influence of a decline in the capacity of short-term memory, and a loss of efficiency in suppression mechanisms.

Aged↗

The effects of noradrenergic re-uptake inhibition on memory encoding in man.

RATIONALE: Animal and human evidence implicate the central noradrenergic system in the process of memory modulation for emotional material. Blockade of the beta-adrenergic system in humans has been shown to result in decreased recall and recognition memory performance, relative to placebo, for the emotional elements of a series of slides accompanied by a narrative. Stimulation of the noradrenergic system with yohimbine has also been shown to result in increased recall and recognition performance relative to placebo for the same stimulus materials. OBJECTIVES: The present study tested the hypothesis that stimulating the central noradrenergic system using the new noradrenaline re-uptake inhibitor reboxetine would result in a dose-dependent enhancement of memory for emotional material in man. METHODS: The central noradrenergic system was manipulated using reboxetine in a double-blind, randomised between-group, placebo-controlled design with 36 healthy adult subjects in each of three groups (placebo, 4 and 8 mg reboxetine). Free recall and recognition memory performance were assessed in a 'surprise' memory test following a 7-day interval. RESULTS: We found no memory enhancing effect of reboxetine. In contrast we observed a dose-dependent effect on memory opposite to the predicted direction. There were no significant differences between groups in self-rated stress and arousal scores or self-rated emotional reactions to the stimuli. All groups showed the expected increased memory performance for the middle 'emotive' phase of the story. CONCLUSION: Selective stimulation of the central noradrenergic system at encoding did not result in enhanced long-term memory for emotional material in man.

Adrenergic Uptake Inhibitors↗

Chronic inhibition of alpha4beta2 nicotinic receptors in the ventral hippocampus of rats: impacts on memory and nicotine response.

RATIONALE: Acute and chronic systemic nicotine administration has been shown to cause significant spatial memory improvement. The critical nicotinic receptor subtypes for this effect and their location are still being determined. Nicotinic receptors in the ventral hippocampus have been found to be critically involved in memory. Acute ventral hippocampal infusions of dihydro-beta-erythroidine (DHbetaE), an alpha4beta2 nicotinic receptor antagonist, impaired spatial memory of rats in the radial-arm maze. OBJECTIVES: The current study used chronic ventral hippocampal infusion of DHbetaE as a model of nicotinic receptor loss such as that which occurs in Alzheimer's disease. The therapeutic effect of systemic nicotine treatment in reversing the DHbetaE-induced memory impairment was determined. METHODS: Rats were pretrained to asymptotic levels of performance on the eight-arm radial maze. Then, they were implanted with bilateral infusion cannulae in the ventral hippocampus, through which 0, 33.3, or 100 microg/side/day of DHbetaE was continuously infused for 4 weeks. The rats were retested on the eight-arm maze throughout infusion period and after withdrawal, and the interaction of acute systemic nicotine injections on memory was tested. RESULTS: The higher (100 microg/side/day) but not the lower (33.3 microg/side/day) DHbetaE dose caused a significant spatial memory impairment. Acute systemic nicotine injections (0, 0.1, 0.2, and 0.4 mg/kg, subcutaneous) attenuated the memory impairing effects of 100 microg/side/day of DHbetaE. There was no significant effect on response latency with the chronic DHbetaE infusion. Acute systemic nicotine infusions did significantly speed responding, an effect which was reversed by chronic hippocampal infusions of DHbetaE. After withdrawal there were no significant lasting effects on choice accuracy or response latency. Wet-dog shakes were significantly elevated during chronic hippocampal DHbetaE administration with no effect during the withdrawal period. CONCLUSIONS: These results indicate that chronic inhibition of a subset of nicotinic receptors in the hippocampus results in a significant impairment in the spatial memory choice accuracy. The ability of nicotine to attenuate the impairment supports the development of nicotinic agonist therapy of syndromes, such as Alzheimer's disease, that involve a chronic decrease in the activity of the alpha4beta2 nicotinic receptors and memory impairment.

Alzheimer Disease↗

Infralimbic kappa opioid and muscarinic M1 receptor interactions in the concurrent modulation of anxiety and memory.

RATIONALE: Spontaneous working memory and anxiety-like behaviour can be concurrently influenced following kappa opioid or muscarinic M1 antagonist infusions in the infralimbic (IL) area of the ventromedial prefrontal cortex (vmPFC) in CD-1 mice. Further dose-response analyses of our previous norBNI and pirenzepine data revealed significant dose x drug interactions on trial-1 and -2 anxiety-related elevated plus-maze indices. These data prompted us to evaluate the effects of simultaneous IL norBNI/pirenzepine infusions on anxiety and spontaneous working memory. OBJECTIVE: The present study sought to evaluate whether (a) our previously reported anxiogenic and working memory disruptive effects of norBNI, and anxiolytic and working memory disruptive effects of pirenzepine data could be replicated using the most effective dose (10 nmol) of each drug and (b) IL infusions of mixed kappa/M1 receptor inhibitor drugs might interactively influence these cognitive, behavioural processes. METHODS: Anxiety was evaluated in the elevated plus maze, and spontaneous alternation memory was evaluated in the Y-maze following pirenzepine, norBNI or two levels of norBNI/pirenzepine drug mix infusions in the IL vmPFC. RESULTS: Pretreatment with the M1 antagonist pirenzepine was anxiolytic in trial 1 (10 nmol) and trial 2 (no-injection) in the elevated plus maze 24 h later, and disrupted alternation performance and some aspects of attention in the Y-maze. Pretreatment with the kappa antagonist norBNI was anxiogenic in trial 1 (10 nmol) and trial 2 (no-injection) in the elevated plus maze 24 h later, and also disrupted alternation performance and some aspects of attention in the Y-maze. The norBNI-10 nmol/pirenzepine-10 nmol mixed drug infusion was somewhat anxiogenic in trial 1, exerted no carry-over effects in trial 2 in the elevated plus maze, and disrupted alternation memory and some aspects of attention in the Y-maze. The norBNI-5 nmol/pirenzepine-10 nmol drug mix had no effect on trial-1 or -2 anxiety measures in the elevated plus maze, yet also disrupted Y-maze spontaneous memory performance. CONCLUSIONS: (1) The effects of IL infusions of norBNI or pirenzepine (10 nmol/0.5 microl) alone on anxiety-like behaviour and aversive learning and memory in the elevated plus-maze replicated previously reported data. (2) Mixed M1/kappa receptor inhibition in the IL cortex exerted counteractive effects on anxiety-like behaviour and aversive learning in the elevated plus maze. (3) Mixed M1/kappa receptor inhibition appeared to exert additive disruptive effects on alternation performance and aspects of attention related to active working memory in the Y-maze.

Animals↗

Effects of different doses of glucose and insulin on morphine state-dependent memory of passive avoidance in mice.

RATIONALE: Behavioral effects of morphine, including its effect on memory, have been demonstrated to be influenced by glucose pretreatment. The measurement of step-down latency in passive avoidance has been used to study memory in laboratory animals. The pre-training injection of 5 mg/kg morphine impaired memory, which was restored when 24 h later the same dose of the drug was administered. OBJECTIVES: To investigate the effects of glucose and insulin alone or in combination with morphine, on pre-test day, on memory recall in mice. METHODS: The effects of different doses of glucose (50, 100, and 200 mg/kg, IP) and insulin (5, 10, and 20 IU/kg, IP) alone or in combination with morphine, have been studied in mice. The blood glucose level and locomotor activity of the animals were also measured. RESULTS: Although the administration of glucose alone showed no effect on morphine-induced memory impairment, its co-administration with morphine resulted in a significant and dose-dependent memory enhancement compared with the effects of morphine administration alone. Like glucose, the administration of different doses of insulin alone produced no change in the memory, but when the drug was co-administered with morphine, it significantly reduced morphine-induced memory retrieval. The effect of insulin was the opposite of glucose. None of the animals subjected to insulin treatment showed convulsions. CONCLUSIONS: Glucose is suggested to increase, on the test day, the morphine-induced memory enhancement by three different mechanisms: cholinergic or opioidergic modulations, or regulation of the ATP-dependent potassium channels.

Analgesics, Opioid↗

Impairment of specific episodic memory processes by sub-psychotic doses of ketamine: the effects of levels of processing at encoding and of the subsequent retrieval task.

RATIONALE: The precise nature of the impact of the N-methyl-D-aspartate antagonist, ketamine, upon human episodic memory, has yet to be elucidated fully. OBJECTIVES: This study sought to assess the effects of ketamine on the sub-processes facilitating memory encoding and retrieval. METHODS: We evaluated the effects of the drug on a series of memory performance measures depending upon whether it was administered at the encoding or retrieval stage and on the nature of the encoding task used. Twelve healthy volunteers participated in a double-blind, placebo-controlled, randomized, within-subjects study. Intravenous infusions of placebo, 50 ng/ml ketamine or 100 ng/ml ketamine were administered. We investigated the effects of ketamine on three key aspects of episodic memory: encoding vs retrieval processes, source memory, and depth of processing. Data were analysed using both multinomial modelling and standard measures of item discrimination and response bias. RESULTS: Deleterious effects of ketamine on episodic memory were primarily attributable to its effects on encoding, rather than retrieval processes. Recognition memory was impaired for items encoded at an intermediate level of processing, but preserved for shallowly and deeply encoded items. Increased source guessing bias was also observed when encoding took place under ketamine. CONCLUSIONS: The effects of ketamine upon episodic memory seem, therefore, to predominate at encoding. Furthermore, our results are also consistent with a specific impairment of encoding processes that result in subsequent recollective, as opposed to familiarity-based, retrieval. The observed effects are compatible with memory deficits seen in schizophrenia and thus provide some support for the ketamine model of the disease.

Adolescent↗

Modulation of memory and visuospatial processes by biperiden and rivastigmine in elderly healthy subjects.

RATIONALE: The central cholinergic system is implicated in cognitive functioning. The dysfunction of this system is expressed in many diseases like Alzheimer's disease, dementia of Lewy body, Parkinson's disease and vascular dementia. In recent animal studies, it was found that selective cholinergic modulation affects visuospatial processes even more than memory function. OBJECTIVE: In the current study, we tried to replicate those findings. In order to investigate the acute effects of cholinergic drugs on memory and visuospatial functions, a selective anticholinergic drug, biperiden, was compared to a selective acetylcholinesterase-inhibiting drug, rivastigmine, in healthy elderly subjects. METHODS: A double-blind, placebo-controlled, randomised, cross-over study was performed in 16 healthy, elderly volunteers (eight men, eight women; mean age 66.1, SD 4.46 years). All subjects received biperiden (2 mg), rivastigmine (3 mg) and placebo with an interval of 7 days between them. Testing took place 1 h after drug intake (which was around Tmax for both drugs). Subjects were presented with tests for episodic memory (wordlist and picture memory), working memory tasks (N-back, symbol recall) and motor learning (maze task, pursuit rotor). Visuospatial abilities were assessed by tests with high visual scanning components (tangled lines and Symbol Digit Substitution Test). RESULTS: Episodic memory was impaired by biperiden. Rivastigmine impaired recognition parts of the episodic memory performance. Working memory was non-significantly impaired by biperiden and not affected by rivastigmine. Motor learning as well as visuospatial processes were impaired by biperiden and improved by rivastigmine. CONCLUSIONS: These results implicate acetylcholine as a modulator not only of memory but also of visuospatial abilities.

Aged↗

Effects of DHEA administration on episodic memory, cortisol and mood in healthy young men: a double-blind, placebo-controlled study.

RATIONALE: Dehydroepiandrosterone (DHEA) has been reported to enhance cognition in rodents, although there are inconsistent findings in humans. OBJECTIVES: The aim of this study was to investigate the effects of DHEA administration in healthy young men on episodic memory and its neural correlates utilising an event-related potential (ERP) technique. METHODS: Twenty-four healthy young men were treated with a 7-day course of oral DHEA (150 mg b.d.) or placebo in a double blind, random, crossover and balanced order design. Subjective mood and memory were measured using visual analogue scales (VASs). Cortisol concentrations were measured in saliva samples. ERPs were recorded during retrieval in an episodic memory test. Low-resolution brain electromagnetic tomography (LORETA) was used to identify brain regions involved in the cognitive task. RESULTS: DHEA administration led to a reduction in evening cortisol concentrations and improved VAS mood and memory. Recollection accuracy in the episodic memory test was significantly improved following DHEA administration. LORETA revealed significant hippocampal activation associated with successful episodic memory retrieval following placebo. DHEA modified ERPs associated with retrieval and led to a trend towards an early differential activation of the anterior cingulate cortex (ACC). CONCLUSIONS: DHEA treatment improved memory recollection and mood and decreased trough cortisol levels. The effect of DHEA appears to be via neuronal recruitment of the steroid sensitive ACC that may be involved in pre-hippocampal memory processing. These findings are distinctive, being the first to show such beneficial effects of DHEA on memory in healthy young men.

Adolescent↗

Confidence level and feeling of knowing for episodic and semantic memory: an investigation of lorazepam effects on metamemory.

The effects of lorazepam (0.026 or 0.038 mg/kg), a benzodiazepine, and of a placebo on metamemory, i.e. knowledge about one's own memory capabilities, were investigated in 36 healthy volunteers. Accuracy of confidence levels (CL) in the correctness of recalled answers and accuracy of feeling of knowing (FOK) the answers when recall fails were measured using a sentence memory task assessing episodic memory and a task consisting of general information questions and assessing semantic memory. Lorazepam impaired episodic memory. Unexpectedly, it also impaired performance in both the recall and recognition phases of the task assessing semantic memory, suggesting that it decreased the ability to distinguish between correct and incorrect information. In episodic memory, lorazepam 0.038 mg/kg-treated subjects exhibited an impaired CL accuracy, compared to placebo-treated subjects, and their FOK accuracy was at chance. In semantic memory, their overall CL and FOK accuracy was apparently spared. However, these subjects selectively overestimated their CL judgements for incorrect answers; moreover, secondary analyses showed that FOK accuracy for a subset of low-accuracy items was virtually nil. These results suggest that lorazepam impairs metamemory for both episodic and semantic memory.

Adult↗

The cannabinoid CB1 receptor antagonist SR141716A attenuates the memory impairment produced by delta9-tetrahydrocannabinol or anandamide.

The administration of delta9-tetrahydrocannabinol (THC), the principle psychoactive ingredient in marijuana, or the endogenous cannabinoid anandamide, has been shown to impair recent memory. The purpose of the present investigation was to determine if the cannabinoid CB1 receptor antagonist SR141716A could attenuate THC- or anandamide-induced memory impairment, and to assess the effects on memory of SR141716A alone. Memory was assessed in rats well-trained in a two-component instrumental discrimination task, consisting of a conditional discrimination, and a non-match-to-position to assess recent or working memory. SR141716A (0.0-2.0 mg/kg) had no effect on either the conditional discrimination or the non-match-to-position. However, SR141716A (0.0-2.0 mg/kg) attenuated the memory impairment produced by THC (2.0 or 4.0 mg/kg) as indexed by an enhancement of performance in the non-match-to-position. When administered to rats pretreated with anandamide (2.0 mg/kg), SR141716A (0.0-2.5 mg/kg) impaired performance in the conditional discrimination at the highest dose. This was interpreted as a deficit in some capacity unrelated to memory (e.g., motor impairment). However, lower doses of SR141716A (0.1 and 0.5 mg/kg) attenuated the anandamide-induced impairment of performance in the non-match-to-position without affecting the conditional discrimination. This is the first report that the memory impairment produced by anandamide can be attenuated by a cannabinoid antagonist; results suggest that anandamide-induced memory disruption is mediated by CB receptors.

Animals↗

Impairment of memory and plasma flunitrazepam levels.

Flunitrazepam was administered to volunteers in three different oral doses. The effects on psychomotor sedation, attention, working memory and explicit memory were then assessed at various intervals after dosing and compared with levels of the drug in the plasma. Three groups of 12 healthy males with similar levels of education were given placebo or flunitrazepam (1, 2 or 4 mg) in a double-blind, random-sequence study. Volunteers completed a battery of tests at night, 3.5 h after taking the drug and in the morning, 10 h afterward. Blood samples were collected for drug analysis before and after the nocturnal tests and before morning tests. At night, only the highest dose of flunitrazepam (4 mg) induced significant changes in psychomotor sedation, attention, working memory, and prose immediate recall. Doses of 2 and 4 mg flunitrazepam significantly reduced the mean scores of explicit memory (morning tests). Z-scores, calculated from differences between flunitrazepam and placebo, revealed that 2 mg flunitrazepam impaired memory but not alertness or attention. Linear regression analysis of the relationship between plasma levels of flunitrazepam and its effects (Z-scores) indicated that there was a significant positive correlation between peak levels of flunitrazepam at night and impairment of night attention and explicit memory, i.e. delayed recall of prose (r = 0.59, P < 0.01) and trigrams (r = 0.55, P < 0.01). However, memory and attention Z-scores as a function of plasma levels fitted with nonlinear regression analysis to the Emax model had higher correlation coefficients. To produce an effect equal to 50% of the maximum effect for memory impairment, concentrations (EC50) were 6.1 and 6.4 ng/ml for prose and trigrams delayed recall; but for attention they were much higher, at 13.2 ng/ml. The overall results indicate that higher concentrations were needed to impair attention than were required to impair memory.

Adult↗

The acetylcholinesterase inhibitor, ENA 713 (Exelon), attenuates the working memory impairment induced by scopolamine in an operant DNMTP task in rats.

RATIONALE: The disruption of working memory in the delayed non-matching to position (DNMTP) task by the muscarinic antagonist, scopolamine, is considered to be a model of the spatial working memory deficit in Alzheimer's disease (AD) patients. OBJECTIVE: To investigate whether ENA 713 (Exelon) (0.1, 0.5 mg/kg, IP), an acetylcholinesterase inhibitor, would reverse the effects of scopolamine in the DNMTP task. METHODS: Male Lister Hooded rats were trained to criterion in an operant DNMTP task (0- to 16-s delay intervals) before receiving vehicle, scopolamine (0.05 mg/kg, SC) alone, ENA 713 (0.1, 0.5 mg/kg, IP) alone, or combinations of scopolamine and ENA 713, in two variations of the task - with and without barriers inserted between the food magazine and the two levers. Barriers were inserted to prevent the use of positional strategies to perform the task, since this behaviour may confound the conclusions of the effect of drugs on working memory. RESULTS: It was found that: (i) scopolamine significantly reduced choice accuracy delay-dependently in both test situations while modifying non-mnemonic measures of task performance delay-independently, indicating an impairment of working memory; (ii) ENA 713 (0.5 mg/kg) significantly attenuated the scopolamine-induced impairment of working memory and significantly reduced the scopolamine-induced changes in some non-mnemonic measures of task performance; (iii) the presence of barriers did not alter the effects of scopolamine and ENA 713 on working memory. CONCLUSION: ENA 713 reversed the working memory deficit induced by scopolamine. These results are consistent with the attenuation of learning and memory disruptions due to cholinergic dysfunction by ENA 713 in other preclinical assays, and predict a drug-induced improvement in working memory in AD patients.

Animals↗

How should we measure nutrition-induced improvements in memory?

There is a basic distinction between declarative memories, which can be stated verbally, and non-declarative memory, such as how to ride a bicycle, which cannot be expressed in words. With age it is the performance of declarative memory, particularly episodic memory that requires recall of events placed in time, that declines. As memory is not a unitary phenomenon, it should be ideally monitored using a range of tests that reflect theoretical conceptions of the topic. If circumstances demand the use of a single test then a measure of episodic memory is suggested. When it proves only possible to use a rating scale it should be ensured that memory is distinguished from other aspects of cognition and that different types of memory are not confused. The tests used, and the form in which they are used, need to be chosen to be of appropriate difficulty for the sample studied. A major conclusion is that the selection of the measure of memory used in the study of a dietary intervention should never be routine. It is inevitable that the form of the test used will need to be chosen carefully for the population being studied.

Aged↗

Effects of reversible inactivations of the medial septal area on reference and working memory versions of the Morris water maze.

Involvement of the medial septal area (MSA) in reference memory and working memory versions of the Morris water maze (MWM) task was investigated in rats with reversible inactivation of this area by drugs injected through a single cannula aimed at the MSA. In Experiment 1, rats were trained in a reference memory version of the MWM with two blocks of four trials per day for 3 consecutive days. Acquisition was impaired by pretrial MSA injection of 10 ng tetrodotoxin (TTX) in 1 microliter saline but not of saline alone into MSA. In Experiment 2, intraseptal injection of TTX (10 ng, 1 microliter) immediately after two blocks of four trials had no effect on the consolidation of spatial reference memory. In Experiment 3, intraseptal injection of TTX (10 ng, 1 microliter) impaired retrieval of well established spatial reference memory in rats which had received 8 trials per day for 3 consecutive days. In Experiments 4 and 5, rats were trained in a working memory version of MWM task to find a new target position in trial 1 and retrieval of this information was tested 75 min later in trial 2. Intraseptal injection of lidocaine (4%, 1 microliter) prior to training impaired working memory performance while immediately posttraining injection of lidocaine had no effect. It is concluded that normal activity of the MSA is necessary for the memory formation at the time of training but its involvement in posttraining consolidation is unlikely. The MSA function is required for retrieval of well established spatial reference memory.

Animals↗

Cortical DC potential shifts accompanying auditory and visual short-term memory.

Negative DC potential shifts appeared over the scalp during the performance of verbal and non-verbal short-term memory tasks. Three items were successively presented (presentation of memory items) and then had to be retained in memory for 3 sec (memory retention) before being compared to a probe which was either a member (in set) or not a member (out of set) of the memory set. Verbal items (the digits "1" through "9") were tested in the auditory and visual modality and non-verbal items (musical notes) were tested in the auditory modality. Stimulus modality had a significant effect on DC potential shifts during both presentation of memory items and memory retention. There was a sustained negative shift during these periods which was larger over frontal regions with auditory than with visual material whereas the negative shift was larger over posterior temporal regions with visual than with auditory material. Out of 21 subjects who participated in the study, 9 reported the use of visual images in the auditory task, 5 used subvocal auditory rehearsal in the visual task and 7 used imagery concordant with the stimulus modality being memorized. These different strategies had a significant effect on the amplitudes and distribution of the DC potential shifts. The speed of response affected the amplitude of the DC potential shifts in the frontal regions, being larger with fast RTs than with slow RTs but only when verbal items were being processed. These results indicate that stimulus modality, modality of mental imagery, and speed of scanning of the memory store affect DC potential shifts during a 3 sec period of memory retention.

Acoustic Stimulation↗