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PubMed1996

Deficits in spatial working memory after unilateral temporal lobectomy in man.

Forty neurosurgical patients and 20 controls were tested on a series of computerized tasks (the executive golf, structured golf and rotate tasks) designed to investigate spatial working memory. As defined by Olton [Spatial Abilities, Academic Press, New York, 1982], spatial working memory involves the encoding of specific and contextual information within the spatial domain. Right temporal lobectomy patients were significantly impaired on all three tasks, while the left temporal lobectomy patients showed a less significant overall impairment only on the structured golf task. Although there was no statistically significant differences between the two patient groups on the three tasks, the results point towards a robust deficit in spatial memory associated with right temporal lobectomy. The results provide further evidence for the role of the mesial temporal lobe structures in the processing and encoding of spatial information.

Adult↗

PubMed1996

Spatial working memory is preserved in rats treated with anabolic-androgenic steroids.

The effects of anabolic-androgenic steroid (AAS) compounds on spatial working memory were evaluated in male rats. Thirty days of administration of a high dose of three individual AAS compounds (17 alpha-methyltestosterone, methandrostenolone, or testosterone cypionate) had no effects on spatial memory or motivation as tested on a delayed non-match-to-sample radial arm maze task. Administration of these AAS compounds at doses within the human abuse range does not impair spatial working memory in rats.

Anabolic Agents↗

PubMed2005

High-capacity spatial contextual memory.

Humans show implicit memory for complex spatial layouts, which aids in subsequent processing of these layouts. Research efforts in the past 5 years have focused primarily on a single session of training involving a dozen repeated displays. Yet every day, people encounter many more visual layouts than were presented in such experiments. In this study, we trained subjects to learn 60 repeated displays, randomly intermixed within 1,800 nonrepeated displays, spread over 5 consecutive days. On each day, the subjects conducted visual search on 360 new displays and a new set of 12 repeated displays, each repeated 30 times. Contextual memory was observed daily. One week after the fifth session, the subjects still searched faster on the repeated displays learned previously. We conclude that the visual system has a high capacity for learning and retaining repeated spatial context, an ability that may compensate for our severe limitations in visual attention and working memory.

Adult↗

PubMedDate not supplied

[Spatial synchronization of cerebral cortical potentals at different levels of functioning of short-term verbal memory].

Spatial synchronization of cortical biopotentials was studied at different levels of the functioning of short-term verbal memory. In the phases prior to and during presentation of information the general level of distant synchronization in the cortex at a high functional state of the mnemical mechanism is higher than at a low state. In the phases following presentation and during reproduction, the relations are reverse. The enhancement of distant synchronization involves primarily the posterior parts of the right hemisphere, while the decrease comprises all the cortical areas, with some predominance of this effect in the anterior areas.

Cerebral Cortex↗

PubMed2004

Non-NMDA mechanism in the inhibition of cellular apoptosis and memory impairment induced by repeated ischemia in rats.

The spatial memory impairment and expression of apoptotic cells in hippocampal CA1 cells were investigated in rats using single and repeated ischemia models. The neuroprotective and memory-improving effect of YM-90K, an alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA) receptor antagonist, was compared to MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist. Twice-repeated ischemia, but not single ischemia, impaired the spatial memory and increased expression of apoptotic cells. YM-90K, given before and 6 h after the second reperfusion, significantly improved the memory and reduced the apoptotic cells 7 days after the second reperfusion in repeated ischemia. MK-801 neither improved the spatial memory nor reduced apoptotic cells. The present study showed that delayed expression of apoptotic cells is mediated by mechanisms involving AMPA receptors, but not by NMDA receptor, during the late phase after reperfusion. YM-90K could provide neuroprotective activity and improve the spatial memory impaired by repeated ischemia.

Animals↗

PubMed1998

Memory for spatial location: role of the hippocampus in mediating spatial pattern separation.

A paradigm based on measuring short-term memory for spatial location information as a function of spatial similarity between distal cues was developed to examine the role of pattern separation in the modulation of short-term memory for spatial information. A delayed-match-to-sample for spatial location task using a dryland version of the Morris water maze was used to assess spatial pattern separation in male Long-Evans rats. In the sample phase, animals were trained to displace an object that covered a baited food well in one of 15 spatial locations along a row of food wells perpendicular to a start box. In the ensuing choice phase, the animal was allowed to choose between two objects identical to the sample phase object. One covered the same baited food well as did the object in the study phase (correct choice), and another foil object (incorrect choice) covered a different unbaited food well along the row of wells. Five spatial separations were randomly used to separate the correct object from the foil object. After reaching a criterion before the operation, animals were given either hippocampal or cortical control lesions. In trials after the operation, control animals matched their performance before the operation across all spatial separations. In contrast, hippocampal-lesioned animals displayed impairments across all spatial separations with the exception of the longest (105 cm) spatial separation. The results suggest that the hippocampus may serve to separate incoming spatial information by temporarily storing one place separate from another. It is proposed that hippocampal lesions decrease efficiency in pattern separation, resulting in impairments in trials with increased spatial similarity among working-memory representations.

Animals↗

PubMed2005

Testosterone reverses ethanol-induced deficit in spatial reference memory in castrated rats.

The present study was designed to evaluate the effects of ethanol, testosterone and combination of ethanol and testosterone, on spatial reference memory and beta-endorphin (beta-EN) levels in castrated rats. Male Sprague-Dawley rats (120-150 g) were used in this study, Animals were castrated and ethanol, testosterone or combination of the drugs were administered to rats at 09:00 h. The drugs were administered after a training period of 5 days and spatial reference memory was evaluated for 7 days using the Morris water maze. One hour after the last injection, animals were sacrificed, their brains removed and dissected into cortex, hypothalamus, hippocampus and midbrain. The beta-EN levels in these brain regions were determined by radioimmunoassay. The time to find the platform (latency period) was significantly increased in ethanol-treated rats, indicating that ethanol induces deficit in spatial reference memory. On the other hand, testosterone administration improved spatial reference memory by significantly decreasing the latency period. In addition, there was a significant decrease in latency period in the animals treated with combination of ethanol and testosterone. Results also indicate that administration of ethanol resulted in a significant increase in beta-EN levels in the hippocampus and in the cortex while concurrent administration with testosterone abolished this increase. These findings clearly indicate that administration of testosterone did not only improve memory but also abolished the spatial memory deficit induced by ethanol in castrated rats.

Animals↗

PubMed2004

The role of spatial working memory in visual search efficiency.

Many theories have proposed that visual working memory plays an important role in visual search. In contrast, by showing that a nonspatial working memory load did not interfere with search efficiency, Woodman, Vogel, and Luck (2001) recently proposed that the role of working memory in visual search is insignificant. However, the visual search process may interfere with spatial working memory. In the present study, a visual search task was performed concurrently with either a spatial working memory task (Experiment 1) or a nonspatial working memory task (Experiment 2). We found that the visual search process interfered with a spatial working memory load, but not with a nonspatial working memory load. These results suggest that there is a distinction between spatial and nonspatial working memory in terms of interactions with visual search tasks. These results imply that the visual search process and spatial working memory storage require the same limited-capacity mechanisms.

Exploratory Behavior↗

PubMed2003

Reversible inactivation of the hippocampal formation in food-storing black-capped chickadees (Poecile atricapillus).

The role of the hippocampal formation (HF) in memory processing was assessed in food-storing black-capped chickadees (Poecile atricapilla) by reversibly inactivating the HF during different memory tests. The memory tests required birds to remember a location based on spatial cues only, or based on a combination of both spatial and distinct visual cues. Inactivation of the HF impaired short-term spatial memory, but not visual-spatial memory. Inactivation of the HF impaired the retrieval of short-term (15 min) spatial memories, but not long-term (3-h) spatial memories. The pattern of deficits produced by inactivation of the HF in chickadees suggests a possible function of the hippocampal specialization of food-storing birds, as well as extends the notion of functional homology between the avian and mammalian HF.

Animals↗

PubMed2004

Long-term memory for spatial locations in a food-storing bird (Poecile atricapilla) requires activation of NMDA receptors in the hippocampal formation during learning.

Food-storing birds use a form of long-term memory to recover their hidden food caches that depends on the hippocampal formation (HF). The authors assessed whether food-storing birds' long-term memory for spatial locations requires N-methyl-D-aspartate receptor (NMDA-R)-dependent synaptic plasticity. Black-capped chickadees (Poecile atricapilla) were given bilateral infusions of the NMDA-R antagonist AP5 into the hippocampus, and their memory on a spatial reference memory task was assessed. NMDA-R inactivation during learning prevented formation of long-term spatial memories but did not affect short-term memory and retrieval processes. NMDA-R inactivation immediately following learning did not disrupt long-term memory formation. NMDA-R inactivation disrupted the learning of multiple serially encoded reward locations when a 180-min delay separated successive learning episodes, suggesting that NMDA-R activity has a role in the incorporation of new information into existing long-term memory, as well as in forming unitary long-term memories.

Animals↗

PubMed2003

Dopaminergic modulation of visual-spatial working memory in Parkinson's disease.

Visual-spatial working memory (WM) impairment is frequently associated with the early stage of Parkinson's disease (PD). The aim of this study was to evaluate the performance of a group of PD patients in visual-spatial and visual-object WM tasks and to investigate the effect of administering the dopaminergic agonist apomorphine (experiment 1) or the dopamine precursor L-dopa (experiment 2) on the performance of tests assessing these functions. To study WM processes, the PD patients and age-matched normal controls were given an n-back task paradigm. In both experiments, the PD patients were submitted to two evaluations: one after a 12-hour therapy washout and the other 15 min after a subcutaneous infusion of apomorphine (average 0.04 mg/kg) or 20/30 min after L-dopa intake (200 mg p.o.). The apomorphine infusion had a worsening effect on reaction times in both visual-spatial and visual-object WM tasks, but it did not influence performance accuracy. Instead, L-dopa administration had a ameliorative effect on accuracy and reaction times in both visual-spatial and visual-object tasks. These results highlight the role of dopamine in the modulation of the WM function in PD patients.

Apomorphine↗

PubMed1995

Glucocorticoids, hippocampal corticosteroid receptor gene expression and antidepressant treatment: relationship with spatial learning in young and aged rats.

The emergence of cognitive deficits in a subgroup of aged rats is associated with increased hypothalamic-pituitary-adrenal axis activity, decreased hippocampal mineralocorticoid and/or glucocorticoid receptor gene expression and neuronal loss. Short-term treatment with antidepressant drugs in young rats increases hippocampal corticosteroid receptor gene expression. In this study, the effects of chronic antidepressant administration on hippocampal mineralocorticoid and glucocorticoid receptor gene expression and spatial memory in young and aged rats were investigated. Young (eight months) and old (22 +/- 1 months) Lister-hooded rats were ranked according to watermaze performance. Matched pairs of rats were treated with amitriptyline (10 mg/kg) or saline daily for nine weeks, then reassessed in the watermaze. Amitriptyline significantly improved spatial memory in the young rats (33% increase in transfer test time) and increased hippocampal mineralocorticoid, but not glucocorticoid receptor messenger RNA expression. By contrast, in aged rats, amitriptyline had no effect on spatial memory or hippocampal corticosteroid receptor gene expression, either in cognitively unimpaired or cognitively-impaired animals. In aged rats, basal plasma corticosterone levels, which were significantly higher than in young animals, correlated negatively with spatial memory, while hippocampal glucocorticoid receptor mRNA expression correlated negatively with plasma corticosterone levels and positively with spatial memory. Amitriptyline had no significant effect on basal morning plasma corticosterone levels in either young or aged rats, but significantly decreased evening corticosterone levels in aged rats. Our data support the notion that corticosterone exerts a concentration-dependent biphasic influence, via selective activation of hippocampal mineralocorticoid and glucocorticoid receptor, on spatial memory. Amitriptyline improves spatial memory in young rats and increases hippocampal mineralocorticoid receptor gene expression. The lack of amitriptyline effect on spatial memory in aged rats may reflect decreased plasticity of both the synaptic processes underlying spatial memory and the regulation of hippocampal mineralocorticoid/glucocorticoid receptor expression, with mineralocorticoid receptors fully occupied due to elevated basal plasma corticosterone levels (in part a consequence of inadequate glucocorticoid receptor function).

Aging↗

PubMed1996

Nicotinic, muscarinic and dopaminergic actions in the ventral hippocampus and the nucleus accumbens: effects on spatial working memory in rats.

Acetylcholine (ACh) systems have been widely shown to be important for memory. In particular, ACh hippocampal neurons are critical for memory formation, though ACh innervation of other areas such as the nucleus accumbens may also be important. There has also been increasing interest in ACh and dopaminergic (DA) interactions with regard to short-term spatial memory. In a series of studies, we have found that ACh and DA agonists and antagonists given systemically interact to influence memory. The critical neural loci of these interactions are not currently known. In the present study, we used local infusion techniques to examine the role of ACh and DA transmitter systems in the nucleus accumbens and the ventral hippocampus on radial-arm maze (RAM) working memory performance. Into the nucleus accumbens of rats, we infused the nicotinic ACh agonist nicotine, the nicotinic ACh antagonist mecamylamine, the DA agonist apomorphine, or the DA antagonist haloperidol. Into the ventral hippocampus, we infused nicotine, mecamylamine, the muscarinic ACh agonist pilocarpine, or the muscarinic ACh antagonist, scopolamine. The nicotinic ACh and DA interaction was tested by a hippocampal infusion of mecamylamine alone or together with the DA D2 agonist quinpirole given via subcutaneous injection. The results confirmed that both nicotinic and muscarinic ACh receptors in the ventral hippocampus play a significant role in spatial working memory. Blockade of either nicotinic or muscarinic ACh receptors caused significant impairments in RAM choice accuracy. However, infusion of either nicotinic or muscarinic agonists failed to improve choice accuracy. The interaction of DA D2 systems in different with hippocampal nicotinic blockade than with general nicotinic blockade. Systemic administration of quinpirole potentiated the amnestic effect of mecamylamine infused into the ventral hippocampus, whereas it was previously found to reverse the amnestic effect of systemically administered mecamylamine. In contrast to the significant effects of mecamylamine in the hippocampus, no effects were found after infusion into the nucleus accumbens. Nicotine also was not found to have a significant effect on memory after intra-accumbens infusion. Neither the DA agonist apomorphine nor the DA antagonist haloperidol had a significant effect on memory after infusion into the nucleus accumbens. This study provides support for the involvement of nicotinic and muscarinic receptors in the ventral hippocampus in memory function. Ventral hippocampal nicotinic systems have significant interactions with D2 systems, but these differ from their systemic interactions. In contrast, nicotinic ACh and DA systems in the nucleus accumbens were not found in the current study to be important for working memory performance in the RAM.

Animals↗

PubMed2002

Estrogen replacement improves spatial reference memory and increases hippocampal synaptophysin in aged female mice.

Estrogen deficiency during menopause is often associated with memory dysfunction. However, inconsistencies regarding the ability of estrogen to improve memory in menopausal women highlight the need to evaluate, in a controlled animal model, the potential for estrogen to alleviate age-related mnemonic decline. The current study tested whether estrogen could ameliorate spatial reference memory decline in aged female mice. At the conclusion of testing, levels of the presynaptic protein synaptophysin, and activities of the synthetic enzymes for acetylcholine and GABA, were measured in the hippocampus and neocortex. Aged (27-28-month-old) female C57BL/6 mice were given daily subcutaneous injections of 1 microg or 5 microg of beta-estradiol-3-benzoate dissolved in sesame oil. Control mice received daily injections of sesame oil or no injections. Estradiol treatment began 5 days prior to behavioral testing and continued throughout testing. Spatial and non-spatial memory were assessed in the Morris water maze. The 5 microg dose of estradiol significantly improved spatial learning and memory in aged females. The performance of 5 microg females improved significantly more rapidly than that of control females; estradiol-treated females performed at asymptotic levels by session 2. Furthermore, 5 microg females exhibited a more robust spatial bias than controls during probe trials. In contrast, 1 microg of estradiol did not improve spatial task performance. Neither dose affected performance of the non-spatial task. In the hippocampus, synaptophysin was increased in 5 microg females relative to controls. Estrogen did not affect enzyme activities in either brain region. This study is the first to examine the effects of estrogen replacement on spatial reference memory and synaptophysin expression in aged post-estropausal female rodents. The results suggest that: (1) estrogen can profoundly improve spatial reference memory in aged females, and (2) this improvement may be related to increased hippocampal synaptic plasticity, but not modulation of the synthetic enzymes for acetylcholine and GABA.

Aging↗

PubMed1983

Spatial working memory in rats: effects of monoaminergic antagonists.

To assess the possible involvement of the monoaminergic neurotransmitters norepinephrine, dopamine and serotonin in the maintenance of spatial working memory rats were treated with antagonists 0 or 2 hr after completing the first 4 choices in an 8 arm maze. Haloperidol (0.25-1 mg/kg), when administered 2 hr after Choice 4, produced a small but consistent impairment in performance on retention tests given 5 hr after the first 4 choices. This deficit closely resembled natural forgetting in terms of the type of errors committed. By contrast, haloperidol in the same doses given 0 hr after Choice 4 or 3 hr before the first 4 choices did not affect retention. Likewise treatment with propranolol (10-20 mg/kg), phentolamine (5-20 mg/kg) or methysergide (5-15 mg/kg) did not impair spatial memory, regardless of when these drugs were injected within the session. Evidently dopaminergic neuronal systems are important in the maintenance of normal spatial working memory.

Animals↗

PubMed1982

Scopolamine does not disrupt spatial working memory in rats.

The importance of cholinergic systems for spatial working memory was examined by injecting scopolamine at varying times during a 5 hr-long retention interval imposed between the rat's fourth and fifth choices in an 8 arm maze. Regardless of whether or not the testing procedure required the rats to adopt a spatial solution for the task, scopolamine (1.0-5.0 mg/kg) did not impair retention in a manner that was suggestive of an effect on working memory. Modest deficits observed in some conditions appeared to result from drug effects on performance. Previous findings of impaired acquisition of accurate spatial behavior by scopolamine-treated rats evidently reflect an influence of the drug on physiological systems other than those necessary to maintain working memory for spatial information.

Animals↗

PubMed1998

Effects of huperzine A on nucleus basalis magnocellularis lesion-induced spatial working memory deficit.

AIM: To study the effects of huperzine A on nucleus basalis magnocellularis (NBM) lesion-induced spatial working memory impairment. METHODS: A delayed-non-match-to-sample radial arm maze task was used to study spatial working memory. The choline acetyltransferase (ChAT) activity was determined by the conversion of [3H]acetyl-CoA to [3H]ACh. RESULTS: Unilateral NBM lesion by kainic acid 0.02 mumol impaired rat's ability to perform this working memory task as evidenced by fewer correct choices after different delay intervals and more total errors to complete the task. This behavioral impairment associated with a decrease in the activity of ChAT by about 40% in the ipsilateral cerebral cortex. Huperzine A (0.2 mg.kg-1 i.p. 30 min before testing) ameliorated this spatial working memory impairment. Physostigmine (0.2-0.3 mg.kg-1 i.p. 20 min before testing) also attenuated the NBM lesion-induced memory deficit. CONCLUSION: The integrity of NBM is critical for spatial working memory processing, and this working memory impairment induced by NBM lesion can be ameliorated by huperzine A and physostigmine.

Alkaloids↗

PubMed1994

Hippocampal and amygdaloid involvement in nonspatial and spatial working memory in rats: effects of delay and interference.

Parametric manipulations of the task demand were used to examine the role of the hippocampus and amygdala in nonspatial and spatial working memory in rats. Hippocampal lesions produced an immediate and long-lasting impairment of nonspatial working memory in an operant task. The memory deficits increased as the delay interval and the amount of proactive interference increased. Hippocampal lesions severely impaired spatial working memory in spatial alternation. Extensive postoperative testing reduced the magnitude of impairment of nonspatial but not spatial working memory. Amygdaloid lesions did not impair any aspect of performance in 2 tasks. The results suggest that the hippocampus, but not the amygdala, is involved in working memory and the task demand is a critical determinant for observing impairments of nonspatial working memory following hippocampal lesions.

Amygdala↗