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At least 703 records · Page 39Linked to original sources
PubMed1998

Intraseptal injections of 192 IgG saporin produce deficits for strategy selection in spatial-memory tasks.

The involvement of the cholinergic septohippocampal system in strategies used to reach a spatial goal was examined by functionally inactivating this system with infusions of 192 IgG saporin, a potent cholinergic immunotoxin. Rats were initially trained on a win-shift radial arm maze (RAM) task and then given injections of either 192 IgG saporin (LES) or saline vehicle (CON) into the medial septum and vertical limb of the diagonal band. Rats were then retested postoperatively on the RAM to assess whether allocentric spatial strategies used to solve the task were impaired. The results indicated that injections of 192 IgG saporin into the septum of rats produced deficits in allocentric strategies used to locate the spatial goal when retested. In addition, place and response learning was also examined in a modified version of the Morris water maze task. In this task, rats with cholinergic lesions were mildly impaired in their ability to learn a place response. In order to clarify further whether rats may have been relying on allocentric or egocentric learning strategies to locate the platform, a probe trial was given on the final test day in which the visible platform was moved to a new location. Control rats swam either to the new platform location or the old platform location indicating the use of both an allocentric and egocentric response. However, rats with the cholinergic septal lesions swam to the new platform location indicating an egocentric response. Taken together, these results suggest that selective cholinergic lesions of the septum produce deficits in spatial strategies used to locate a spatial goal.

Animals↗
PubMed1996

Spatial memory impairment induced by lesion of the mesohippocampal dopaminergic system in the rat.

The hippocampal formation has long been thought to play a role in learning and memory. Previous studies from our laboratory examined the organization of mesencephalic projections to the hippocampal formation in the rat. In order to evaluate the effects on learning and memory of retrograde selective lesions of mesencephalic dopaminergic neurons, following bilateral injection of 6-hydroxydopamine in the dorsal and ventral subiculum and adjacent CA1 field of the hippocampal formation, young adult Sprague-Dawley rats were trained in classical inhibitory avoidance, inhibitory avoidance using a multiple trial (training to criterion) and the standard Morris water maze task (cued and spatial versions). With regard to inhibitory avoidance, retention was examined one, three and 10 days after training. Concerning the Morris water maze task, 6-hydroxydopamine-lesioned and sham-operated rats received four training trials on each of four days. After training sessions, the rats were tested during a 60-s probe trial (free-swim trial) in which the platform was removed from the maze. The loss of mesencephalic dopaminergic neurons in the 6-hydroxydopamine-lesioned rats, compared to sham-operated rats, was verified by tyrosine hydroxylase immunohistochemistry. Although the 6-hydroxydopamine-lesioned rats were indistinguishable from sham-operated rats in performing the inhibitory avoidance and the cued version of the Morris water maze task, in the spatial version of the Morris water maze, lesioned rats, compared to controls, exhibited significant differences in the latency (P < 0.05), quadrant time (P < 0.01) and number of platform crossings (P < 0.05). These results suggest that the rat's ability to acquire spatial learning and memory for place navigation in the Morris water maze is likely to be dependent also on the integrity of mesohippocampal dopaminergic connections.

Animals↗
PubMed1996

Posttraining intrahippocampal estradiol injections enhance spatial memory in male rats: interaction with cholinergic systems.

Male Long-Evans rats received an 8-trial training session in a spatial water maze task, followed by a unilateral posttraining intrahippocampal injection of either estradiol (1.0 microgram/0.5 microliter) or saline. Retention was tested 24 hr later, and latency to escape was used as a measure of memory. Retention test escape latencies of rats given intrahippocampal injections of estradiol were lower than those of saline-treated rats, indicating an enhancement of memory. Intrahippocampal injections of estradiol delayed 2 hr posttraining did not affect retention. In Experiment 2, the memory enhancing effect of intrahippocampal injection of estradiol was blocked by peripheral administration of a subeffective dose (0.1 mg/kg) of the cholinergic antagonist scopolamine. Intrahippocampal injections of estradiol enhance memory in male rats, and estradiol may influence memory through an interaction with muscarinic cholinergic systems.

Animals↗
PubMed1998

Place field dynamics and directionality in a spatial memory task.

In previous studies place fields have been shown to be governed by one or more polarizing stimuli such that rotation of the stimuli caused concomitant rotation of the fields. Place fields have also been observed to persist after removal of stimulus cues. In the present study we confirm the previous findings and report two new responses. Hippocampal place fields were observed to decrease or cease place specific firing after the removal of the polarizing cues. Others increased or initiated place specific firing after cue removal. Thus in these instances place field location was dependent on the orientation of the polarizing cues but place field magnitude was governed by their presence or absence. A subset of the place fields recorded in the present study were found to display directionality. Place field directionality was found to be governed by the polarizing cues such that cue rotation produced concomitant rotation in the direction of maximal firing. However directionally specific firing was unaffected by cue removal. These results suggest that place field directionality is initially set up by the polarizing cues but is subsequently independent of them.

Action Potentials↗
PubMed1992

[Study of the role of different types of glutamate receptors in spatial memory in rats].

A comparative study was performed to assess effects of different antagonists of glutamate receptors on spatial discrimination of rats in 8-arm radial and water mazes. Noncompetitive NMDA receptor blocker MK-801 in the dose 0.10 mg/kg and higher impaired the accuracy of performance in radial maze, whereas in the doses 0.05--0.30 mg/kg in water maze. Quisqualate IAMPA- and 2-amino-4-phosphonobutyrate (2-APB) I antagonists glutamate diethyl ester (250--500 mg/kg) and 2-APB (50--100 mg/kg), respectively, only increased time to complete radial maze performance and failed to alter choice accuracy. Both antagonists at the same doses did not affect performance of water maze task. The involvement of each type of glutamate receptors in different stages of spatial discrimination process in rats was discussed.

Animals↗
PubMed1994

Two neuronal systems involved in short-term spatial memory in monkeys.

The investigation of the neuronal activity in the monkey cerebral cortex during the delayed spatial choice performance allowed us to develop the hypothesis about two neuronal networks supporting the operative memory. The work of one of them is based on the relay-race and reverberation principles of information transfer. Another neuronal network provides for the reliability of transfer phases of these processes. The two networks are present in both prefrontal and parietal association cortical area.

Animals↗
PubMed1998

Independent reference frames in human spatial memory: body-centered and environment-centered coding in near and far space.

Our apparently seamless experience of the spatial environment seems to be derived from information coded across a variety of spatial reference frameworks, each tied to the metric of a different sensory or motor system. A fundamental distinction is that between body-centered and environment-centered reference frameworks. This study reports the first clear evidence of a behavioral dissociation between body-centered and environment-centered coding in human adults. Subjects, seated in a rotating chair with closed eyes, were required to point to remembered, auditorily presented target locations. The subjects were rotated between the presentation and recall of targets. Targets were held stationary with respect to either body-centered or environment-centered spatial coordinates. Prior to recall, subjects were required to point to a series of prelearned distractor locations, which also remained fixed with reference either to the subject's body or to the stationary environment. Memory for the target locations was selectively impaired when distractor locations were specified within the same spatial reference frame as the target, regardless of whether target and distractor locations were near to or distant from the subjects. In contrast, distractor locations specified in a different reference frame from that of the target had either little or no effect on memory for target locations.

Adult↗
PubMed1990

Testosterone fails to reverse spatial memory decline in aged rats and impairs retention in young and middle-aged animals.

Recently, the vasopressin (AVP) innervation in the rat brain was shown to be restored in senescent rats following long-term testosterone administration. In order to investigate whether this restoration is accompanied by an improvement in learning and memory, both sham- and testosterone-treated young (4.5 months), middle-aged (20 months), and aged (31 months) male Brown-Norway rats were tested in a Morris water maze. All animals learned to localize a cued platform equally well, indicating that the ability to learn this task was not affected by sensory, motoric, or motivational changes with aging or testosterone treatment. There were no significant differences in retention following cue training. Subsequent training with a hidden platform in the opposite quadrant of the pool (place training) revealed impaired spatial learning in middle-aged and aged animals. Retention following place training was significantly impaired in the sham-treated aged rats as compared with sham-treated young rats. Testosterone treatment did not improve spatial learning nor retention of spatial information, but, on the contrary, impaired retention in young and middle-aged animals. The present results confirm earlier reports on an impairment of spatial learning and memory in senescent rats but fail to support a role of decreased plasma testosterone levels and central AVP innervation in this respect.

Aging↗
PubMed1985

Scopolamine degrades spatial working memory but spares spatial reference memory: dissimilarity of anticholinergic effect and restriction of distal visual cues.

The influence of the centrally active anticholinergic, scopolamine hydrobromide, on working and reference memory was studied in rats tested in a 12-arm radial maze. Both 0.25 and 0.5 mg/kg doses of the drug increased the number of working memory (WM) errors but had no effect on reference memory (RM) errors. A lower dose (0.125 mg/kg) was ineffective, as was the peripherally active anticholinergic, scopolamine methylbromide (0.5 mg/kg). Some of the behavioral effects of anticholinergics on spatial memory are mimicked by blindness or eliminating distal visual cues. If distal visual cues were more important for maintaining accurate WM than for RM, the selective effect of scopolamine on WM could be easily explained. But surrounding the maze with a curtain to eliminate extramaze cues increased RM errors without significantly increasing WM errors. Thus, the selective effect of anticholinergies on spatial memory in the radial maze is qualitatively different from the effect of restricting distal visual cues and must arise from some other action of the drug.

Animals↗
PubMed1981

Deficits in spatial memory performance induced by early undernutrition.

Recent studies have shown that rats have a remarkable ability to keep track of their spatial location. Explanations stress the involvement of a form of short-term (working) memory in which the hippocampus appears to play a major role. The hippocampus appears to be vulnerable to early undernutrition and preliminary investigations indicate that Areas CA3 and CA4 suffer the most. Ninety-day-old rats, previously undernourished prenatally and throughout lactation, were tested in an 8- and, then, a 16-arm radial maze. Significant differences were observed between the experimental and control groups on both tests, especially in the 16-arm maze. Error distributions were also significantly different with experimental animals tending to perseverate in 1 area of the maze. Differences were also observed in the time taken to make the choices and in exploratory behavior. We conclude that early undernutrition affected the spatial learning ability of the animals and that this may be due to the distortions observed in the normal growth pattern of the hippocampus.

Animals↗
PubMed2004

Reduced cortical noradrenergic neurotransmission is associated with increased neophobia and impaired spatial memory in aged rats.

In the present study, young (5-month-old (mo)) and aged (24 mo) adult male Fischer-344 (F344) rats were assigned to experimental groups based upon their performance of a reference memory task in the Morris water maze and reactivity to a novel palatable taste in a gustatory neophobia task. Levels of norepinephrine (NE) and its metabolite 3-methoxy-4-hydroxy-phenylglycol (MHPG) were assayed via high performance liquid chromatography (HPLC) in brain regions associated with the locus coeruleus (LC)-hippocampus-cortex system and A1/A2-hypothalamic system. Binding of ligands specific for alpha-1, alpha-2, beta-1, and beta-2 receptors was assessed in hippocampus and cortex with receptor autoradiography. Impaired acquisition and retention of the water maze task and gustatory neophobia in aged rats was primarily associated with decreased NE activity in cingulate cortex (CC) as indicated by a significant reduction in the MHPG/NE ratio coupled with increased NE content. No significant changes in adrenergic receptor binding were detected in any region sampled. The results suggest that an aging-related reduction in cortical NE neurotransmission is associated with the expression of increased neophobia and deficits in spatial learning and memory performance occurring with advanced age in rats.

Adrenergic alpha-Agonists↗
PubMed1997

Neural Network Model of Spatial Memory: Associative Recall of Maps.

This paper offers a neural network model that can memorize and recall spatial maps. When driving through a place we have been before, we can recall and imagine the scenery that we cannot see yet but shall see soon. Triggered by the newly recalled image, we can also recall other scenery further ahead of us. The model emulates such a chain process of recalling using a correlation matrix memory. A correlation matrix memory by itself, however, does not accept shifts in location of stimulus patterns, and each stimulus pattern has to be placed accurately at the location of one of the memorized patterns. We propose adjusting the location of the stimulus pattern using the cross-correlation between the stimulus pattern and the "piled pattern", which is the sum of all patterns memorized in the correlation matrix. A map of Europe is divided into a number of overlapping segments, and these segments are memorized in the proposed model. Triggered by an input image, say a map around Scotland, the model can recall maps of other parts of Europe sequentially up to Italy, for example. Copyright 1997 Elsevier Science Ltd.

Journal Article↗
PubMed2006

Enhancement of long-term spatial memory in adult rats by the noncompetitive NMDA receptor antagonists, memantine and neramexane.

Memantine and neramexane are noncompetitive NMDA receptor antagonists which have been investigated for their promising effects in aiding memory in people with dementia. Memantine is approved for the treatment of Alzheimer's disease, and neramexane is currently under development for this indication. Therefore, the present study provided a comparative assessment of the effects of equimolar doses of memantine and neramexane on spatial (hippocampus-dependent) memory. Adult male rats were given only 3 training trials to learn the location of a hidden platform in a water maze. In control (vehicle-injected) rats, this minimal amount of training produced intact short-term (15 min), but poor long-term (24 h), memory. Pre-training administration of memantine or neramexane produced a dose-dependent enhancement of long-term memory. Pharmacokinetic experiments with equimolar doses of both agents indicated that lower plasma levels of neramexane were more effective than memantine at enhancing memory. The effective doses of both agents in the current study produced plasma levels (and extrapolated brain CSF levels) within a range of activity at NMDA receptors and plasma levels seen in patients with Alzheimer's disease. These findings provide support for the use of neramexane as a pharmacological intervention in the treatment of dementia.

Alzheimer Disease↗
PubMed2005

Right parietal contributions to verbal working memory: spatial or executive?

The left inferior parietal cortex has been claimed to be the site of the verbal short-term store, yet imaging studies report activity of a homologous right-hemisphere region in verbal working memory tasks as well. In spite of its prevalent activity, right parietal contributions to verbal working memory are poorly understood. To clarify its role in verbal working memory performance, we tested a patient with a lesion in the right parietal lobe on verbal and spatial versions of the N-back task. The patient was impaired in all the spatial conditions regardless of load (0-, 1-, and 2-back), whereas in the verbal N-back he was impaired only in the conditions with a memory demand (1- and 2-back). Given that we had presented stimuli at multiple locations in the verbal N-back, however, it remained possible that the lesion impaired spatial representation rather than verbal working memory per se. With central stimulus presentation, his performance dramatically improved indicating that his difficulty with the N-back task was largely due to his poor visuospatial abilities.

Aged↗
PubMed1993

Hippocampus, theta, and spatial memory.

The past 18 months have witnessed interesting developments in several areas of hippocampal research. First, the mechanisms of hippocampal theta are becoming clear, as is its role in spatial coding; each theta cycle appears to act as a clock mechanism against which the firing of the place cells can be timed. Second, there has been a continued strengthening in the support for the spatial theory of hippocampal function from single unit and lesion experiments; particularly important is the finding that the deficit in (non-spatial) delayed non-match to sample memory experiments in the monkey following medial temporal lobe damage stems from the part of the cortex which surrounds the hippocampus, and not from the hippocampus itself. Third, in contrast, it is proving more difficult than originally thought to show a causal relationship between long-term potentiation at the synaptic level and place learning-induced changes in hippocampal synapses.

Animals↗
PubMed1995

Systemic or intrahippocampal cannabinoid administration impairs spatial memory in rats.

The purpose of the present study was to investigate the disruptive effects of cannabinoids on working memory as assessed in the eight-arm radial-maze. Systemic administration of delta 9-THC, WIN-55,212-2, and CP-55,940 increased the number of errors committed in the radial-maze. CP-55,940 was the most potent cannabinoid in impairing memory (ED50 = 0.13 mg/kg). delta 9-THC and WIN-55,212-2 disrupted maze-choice accuracy at equipotent doses (ED50 values = 2.1 and 2.2 mg/kg, respectively). In addition, systemic administration of each of these agents retarded completion time. Whereas the doses of delta 9-THC and CP-55,940 required to retard maze performance were higher than those needed to increase error numbers, WIN-55,212-2 was equipotent in both of these measures. On the other hand, neither anandamide, the putative endogenous cannabinoid ligand, nor cannabidiol, an inactive naturally occurring cannabinoid, had any apparent effects on memory. A second aim of this study was to elucidate the neuroanatomical substrates mediating the disruptive effects of cannabinoids on memory. Intrahippocampal injections of CP-55,940 impaired maze performance in a dose-dependent manner (ED50 = 8 micrograms/rat), but did not retard the amount of time required to complete the maze. The effects of intrahippocampal CP-55,940 were apparently specific to cognition because no other cannabinoid pharmacological effects (e.g., antinociception, hypothermia, and catalepsy) were detected. This dissociation between choice accuracy in the radial-maze and other cannabinoid pharmacological effects suggests that the working memory deficits produced by cannabinoids may be mediated by cannabinoid receptors in the hippocampus.

Analgesics↗
PubMed1988

Galanin impairs acquisition but not retrieval of spatial memory in rats studied in the Morris swim maze.

The effect of intraventricular administration of the neuropeptide galanin on acquisition and retrieval in a modified Morris swim maze was studied in rats. Galanin induced a significant deficit in the acquisition of the task while no effects on the retrieval were observed. No deficits were seen 24 h after the last treatment. Galanin did not increase the number of failures to reach the platform. It is suggested that endogenous galanin modulates learning possibly via the galanin-containing cholinergic neurons in the septum-basal forebrain area projecting to the hippocampus and cortex.

Animals↗
PubMed2004

External and body-centered frames of reference in spatial memory: evidence from touch.

The study reports independent effects of external and body-centered reference cues on spatial coding of an irregular sequence of haptic locations. The aim was to investigate the nature of spatial coding by using a modality that does not provide distal cues routinely. Our method isolates and combines body-centered and external spatial reference cues for irregularly placed locations, scanned along a raised-line route. Disrupting body-centered reference for the locations, by orienting the map differently to the body in the test phase than in the presentation phase, doubled errors in positioning the locations along the route in recall. Adding external reference, by giving instructions to use a surrounding frame for reference when body-centered coding was disrupted, reduced errors to near baseline (no-rotation) levels. Adding external reference cues to intact (not displaced) body-centered reference halved errors, as compared with the baseline. The results are consistent with the hypothesis that accurate spatial coding is determined by the congruence of potential reference cues from diverse sources. The new findings suggest that external and body-centered reference cues have independent additive effects on spatial coding. The sequence of locations had a significant effect in all the reference conditions, suggesting the additional use of fortuitous but distinctive local touch cues on the route. The discussion considers theoretical and practical implications of the results.

Adolescent↗