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At least 793 records · Page 44Linked to original sources
PubMed1999

Brain insulin receptors and spatial memory. Correlated changes in gene expression, tyrosine phosphorylation, and signaling molecules in the hippocampus of water maze trained rats.

Evidence accumulated from clinical and basic research has indirectly implicated the insulin receptor (IR) in brain cognitive functions, including learning and memory (Wickelgren, I. (1998) Science 280, 517-519). The present study investigates correlative changes in IR expression, phosphorylation, and associated signaling molecules in the rat hippocampus following water maze training. Although the distribution of IR protein matched that of IR mRNA in most forebrain regions, a dissociation of the IR mRNA and protein expression patterns was found in the cerebellar cortex. After training, IR mRNA in the CA1 and dentate gyrus of the hippocampus was up-regulated, and there was increased accumulation of IR protein in the hippocampal crude synaptic membrane fraction. In the CA1 pyramidal neurons, changes in the distribution pattern of IR in particular cellular compartments, such as the nucleus and dendritic regions, was observed only in trained animals. Although IR showed a low level of in vivo tyrosine phosphorylation, an insulin-stimulated increase of in vitro Tyr phosphorylation of IR was detected in trained animals, suggesting that learning may induce IR functional changes, such as enhanced receptor sensitivity. Furthermore, a training-induced co-immunoprecipitation of IR with Shc-66 was detected, along with changes in in vivo Tyr phosphorylation of Shc and mitogen-activated protein kinase, as well as accumulation of Shc-66, Shc-52, and Grb-2 in hippocampal synaptic membrane fractions following training. These findings suggest that IR may participate in memory processing through activation of its receptor Tyr kinase activity, and they suggest possible engagement of Shc/Grb-2/Ras/mitogen-activated protein kinase cascades.

3T3 Cells↗
PubMed1997

Experimental field study of spatial memory and learning in wild capuchin monkeys (Cebus capucinus).

Despite a large body of data on diet and ranging patterns in prosimians, monkeys and apes, little is known regarding the types of information that non-human primates use when making foraging decisions. In a series of controlled field experiments, we tested the ability of wild capuchins (Cebus capucinus) at La Suerte Biological Research Station in north-eastern Costa Rica to remember the spatial positions of 13 feeding platforms and use olfactory and visual cues to identify baited (real bananas) versus sham (plastic bananas) feeding sites. The results indicate that when 'place' was predictable, the capuchins learned the spatial locations of food and non-food sites rapidly (one-trial learning). In a second experiment, the positions of baited feeding sites were random. In the absence of other information, the capuchins used the presence of a local landmark cue (yellow block) placed at reward platforms to select feeding sites. In a final experiment, there was evidence that expectations regarding the amount of food available at a platform (2 bananas vs. 1/2 banana) had a significant influence on capuchin foraging decisions. Although the capuchins were sensitive to changes in experimental conditions, when they were given conflicting cues, spatial information was predominant over other information in selecting feeding sites.

Animals↗
PubMed1997

Experience-dependent facilitating effect of corticosterone on spatial memory formation in the water maze.

Stress-related adrenal steroid hormones modulate brain and cognitive function. Electrophysiological studies, including primed burst potentiation and long-term potentiation, have indicated concentration-dependent inverted U-shape effects of corticosterone in hippocampal function and plasticity. Here, we explored the role of corticosterone in the consolidation and long-term retrieval of spatial learning in the Morris water maze task in rats. We postulated that corticosterone actions might be experience-dependent with regard to stimulus intensity, such as differential water temperatures. Indeed, rats trained at 19 degrees C showed a quicker rate of acquisition and better long-term retention than rats trained at 25 degrees C water. In addition, post-training corticosterone levels, on the first training day, were significantly higher in rats in the 19 degrees C group than in the 25 degrees C group. Performance of rats trained at 25 degrees C, but not at 19 degrees C, water was improved by injecting them i.p. with corticosterone immediately after each training session. Thus, the effect of exogenously administered corticosterone appears to be experience-dependent, with the experience-induced corticosterone concentrations as a critical factor determining the cognitive consequences of steroid treatment. Therefore, this work indicates a facilitating corticosterone action, during the post-training period, on the neural mechanisms determining the strength of information storage under acute, physiological conditions.

Analysis of Variance↗
PubMed1993

Effects of chronic administration of adenosine A1 receptor agonist and antagonist on spatial learning and memory.

Spatial memory acquisition in Morris water maze was tested in C57BL/6 mice. Animals were injected once daily with different doses of either N6-cyclopentyladenosine (CPA) or 8-cyclopentyl-1,3-dipropylxanthine (CPX). Drugs were administered for 9 days either concurrently with water maze testing (drugs injected 1 h after each trial), or prior to the entire block of trials. In the latter case, 1 day without injections preceded water maze experiments. Chronic administration of CPA resulted in a significant, dose-dependent reduction of target latencies, rapid development of spatial preference, and the absence of animals unable to perform the task. CPX treated animals did not show significant performance changes, and failed to develop spatial preference. Locomotor disturbances were not the cause of the observed effects. Our results indicate that chronic treatment with agents acting at adenosine A1 receptors results in behavioral effects that are significantly different from those observed following their acute administration. Therefore, particular caution is required in development of adenosine-based strategies targeted at neurodegenerative or cognitive disorders in which chronic treatment is advocated.

Adenosine↗
PubMed2003

Spatial memory for food hidden by rats (Rattus norvegicus) on the radial maze: studies of memory for where, what, and when.

Rats (Rattus norvegicus) were allowed to hide food items on an 8-arm radial maze by carrying the items from the center to boxes at the end of each arm. Retrieval tests given after rats had hidden 4 items showed that they selectively returned to the maze arms where food had been hidden (Experiments 1 and 2). When rats were allowed to hide pieces of cheese (refed food) and pretzels (less preferred food) on different arms, they both hid and retrieved cheese before pretzels (Experiments 2-5). In Experiment 6, rats chose between arms where cheese and pretzels were hidden,with cheese degraded at one delay interval but not the other. Together, these experiments indicate memory for what and where but not when.

Animals↗
PubMed1990

MK-801 impedes the acquisition of a spatial memory task in rats.

Several studies have reported that MK-801 impairs the acquisition of various learning and memory tasks, while others suggest that MK-801 may interfere with performance rather than having a specific effect on memory. To characterize further the effects of MK-801 on learning and memory, MK-801 (0.05 mg/kg, SC) was administered prior to or immediately after learning trials in a trial-independent water maze task. Since MK-801 may affect nonassociative variables that may influence learning and memory, motor activity and general reactivity measures were also determined for 0.0125, 0.025, or 0.05 mg/kg of MK-801 administered SC. Since MK-801 may also be used to treat children with epilepsy, we investigated the possible persistent cognitive effects on neonates. MK-801 (0.02 mg/kg, SC) was administered at postnatal days 9-15 and tested in the same task as above starting at day 36 of age. There were no persistent effects of neonatal treatment. However, in adult rats, MK-801 impaired the acquisition of the water maze task but did not affect performance during a recall task in the same apparatus. At doses affecting learning, there were no effects on motor activity or general reactivity in adult rats. These results are consistent with the conclusion that MK-801 interferes with acquisition of spatial learning in the rat.

Aging↗
PubMed2004

Nucleus accumbens dopamine receptors in the consolidation of spatial memory.

Nucleus accumbens dopamine is known to play an important role in motor activity and in behaviours governed by drugs and natural reinforcers, as well as in non-associative forms of learning. At the same time, activation of D1 and D2 dopamine receptors has been suggested to promote intracellular events related to neural plasticity. Therefore, in this study we wished to investigate the role of the two classes of dopamine receptors within the nucleus accumbens on the consolidation of spatial information. On day 1, CD1 male mice were placed in an open field containing five different objects and, immediately after three sessions of habituation, the animals were focally injected within the nucleus accumbens with either the D1 antagonist SCH 23390 (12.5, 25 or 50 ng/side), or the D2 antagonist sulpiride (25, 50, 75 or 100 ng/side). Twenty-four hours later the ability of mice to discriminate an object displacement was assessed. Both the D1 and the D2 antagonists impaired the ability of mice to detect the spatial change. If the highest doses of the two antagonists were injected 2 h after the end of the last of the habituation sessions, no effect was observed in the reactivity to spatial change examined 24 h later. These data demonstrate that activation of both D1 and D2 receptors within the accumbens is necessary in the early stages of the consolidation of spatial information. The data are discussed in terms of involvement of nucleus accumbens dopamine in information processing in the absence of explicit reinforcers.

Animals↗
PubMed1983

Can age-related deficits in spatial memory be attenuated through the use of verbal coding?

In a sequential mental rotation task, women of three age groups (18-28, 50-60, and 70-80) viewed semi-abstract figures which were rotated in the picture plane. To investigate the effects of verbal mediation, each figure was presented under one of four labeling conditions. Errors increased as a function of age. Meaningful labels were beneficial in decreasing errors for the older subjects. Reaction time results generally replicated earlier studies, but there were indications that some women in the oldest group might have used strategies other than mental rotation. Results suggest that possible age related deficiencies in spatial abilities may be compensated for by greater use of verbal mediation.

Adolescent↗
PubMed2005

Spatial memory performance in androgen insensitive male rats.

Masculinization of the developing rodent brain critically depends on the process of aromatization of circulating testosterone (T) to its estrogenic metabolite 17beta-estradiol, which subsequently interacts with estrogen receptors to permanently masculinize the brain. However, it remains unclear what role other androgenic mechanisms may play in the process of masculinization. A novel way of examining this is through the study of male rats that express the tfm mutation of the androgen receptor (AR) gene; such males are fully androgen insensitive and manifest a female phenotype due to a failure of AR-mediated masculinization of peripheral structures. Because tfm-affected males develop secretory testes and have near-normal T titers during development, aromatization would be expected to proceed normally, and brain mechanisms may be developmentally masculinized despite the feminized periphery. We compared tfm-affected males (X(tfm)Y) with normal males and females in the Morris Water Maze, a task in which males typically perform better than females. Performance of tfm-affected males was intermediate between that of normal males and females. While an overall male superiority was found in the task, the X(tfm)Y group reached male-typical escape latencies faster than females. Furthermore, in the X(tfm)Y group, the granule cell layer of the dentate gyrus was significantly larger than in females. These results support the suggestion that that AR mediated mechanisms contribute to the masculinization of spatial behaviours and hippocampal morphology, and this may be independent of estrogenic processes.

Analysis of Variance↗
PubMed1990

Locomotion, active choice, and spatial memory in children.

In two studies, children between 4 and 6 years old were tested on a radial search task requiring nonredundant sampling of eight identically labeled positions in a room. In the training phase (5 days), children made free choices by walking between positions, were passively transported in a pushchair, actively directed their own route from a pushchair, or were led on foot to positions selected by the experimenter. When tested (whether walking or directing while seated in a pushchair), children who had either walked independently or directed the experimenter while being pushed performed competently; those led on foot without spatial choice performed almost as well. Only the children who had neither independent locomotor experience nor autonomous choice performed very poorly. The results are related to neurobiological models of spatial cognition and may have implications for the transportation of children with mobility problems.

Child, Preschool↗
PubMedDate not supplied

Behavioral manipulation of retrieval in a spatial memory task for Drosophila melanogaster.

A paradigm for operant conditioning of freely walking single Drosophila flies has been described previously. A fly can be conditioned to avoid one side of a small test chamber if the chamber is heated whenever the fly enters this side. In a subsequent memory test without heat the fly continues to avoid the previously heat-associated side. In this experimental design one cannot exclude that flies mark the heated side by an odor that they subsequently avoid during the test. As a final proof for associative learning in the present experiment, flies are trained in one chamber and tested for learning in another, similar one. Handling in the transfer experiment interferes with memory display, even if the fly is returned to the old chamber instead of a new one. Memory can be reactivated, however, by subjecting the fly to an additional brief training (priming), which is too short to establish significant learning in naive flies. For efficient priming, heat has to be applied to the same side as during training in the old chamber. Only then the fly subsequently shows a side preference and avoids the side of the new chamber, which in the old one had been associated with heat. The two chambers are similar but not identical The transfer experiment therefore raises the question as to what the flies use as spatial reference during training and test. In the light, they can be shown to orientate according to visual landmarks associated with the chamber. In complete darkness, where training and memory scores do not differ from those in the light, they are assumed to use a combination of tactile and idiothetic information for orienting.

Animals↗
PubMed2004

The role of crawling and walking experience in infant spatial memory.

This research explored infants' use of place learning and cue learning in a locomotor task across the transition from crawling to walking. Novice and expert crawling and walking infants were observed in a novel locomotor task-finding a hidden goal location in a large space. In Experiment 1, infants were tested with distal landmarks. Infants with fewer than 6 weeks of experience, either crawling or walking, could not find the goal location. All infants with more locomotor experience were more successful. Learning did not transfer across the transition to walking. In Experiment 2, novice and expert crawlers and walkers were tested with a direct landmark. Again, novice crawlers and walkers with fewer than 6 weeks of experience could not find the goal, whereas those with more experience could. Taken together, these findings suggest that infants' spatial learning is inextricably linked to mode of locomotion.

Child Development↗
PubMed1992

Effects of systemic and intracerebroventricular administration of mecamylamine, a nicotinic cholinergic antagonist, on spatial memory in rats.

The effects of both systemic and intracerebroventricular administration of mecamylamine, a nicotinic antagonist, were tested on the Morris water maze performance of rats. In experiment 1, mecamylamine (0, 3, and 10 mg/kg, IP) was administered before daily training sessions on the Morris water maze, a task in which rats use environmental cues to learn the location of an invisible escape platform in a large pool of water. The escape latencies of rats given the higher dose of mecamylamine were significantly longer than the latencies of rats given either saline or the peripherally-acting nicotinic antagonist hexamethonium (10 mg/kg). Analysis of search patterns during a free swim trial conducted in the absence of an escape platform confirmed the disruptive effects of the higher dose of mecamylamine. Similar drug effects were not observed when these rats were trained to a visible platform, and mecamylamine did not affect the retrieval of spatial information in well-trained rats. In experiment 2, similar effects were observed with ICV administration of mecamylamine (0, 10, 30, and 100 micrograms). The two higher doses increased escape latencies during the last day of place training and all three doses significantly impaired performance on a free swim. No significant effects were noted on subsequent training to a visible platform, and only the highest dose marginally impaired the retrieval of spatial information in well-trained animals. Thus, mecamylamine appears to impair the acquisition of spatial information in the Morris water maze but does not affect retrieval of previously acquired spatial information at comparable doses.

Animals↗
PubMed2000

Passive and active place avoidance as a tool of spatial memory research in rats.

A modified model of the arena described by Bures et al. (Bures J, Fenton AA, Kaminsky Y, Zinyuk L. Place cells and place navigation, Proc. Natl. Acad. Sci. USA. 1997a;94:343-350) was applied to the place learning of adult male rats in two different avoidance paradigms. In the passive avoidance task rats exploring a stationary circular arena had to avoid a 60 degrees sector entering of which was punished by mild footshocks. Intramaze as well as extramaze cues could be used for adequate solution of this task. In the active avoidance paradigm rats were trained to avoid a room frame defined sector (e.g. North-East) of a slowly rotating arena the movement of which forced the animals to rely on extramaze cues and to ignore intramaze information. Rats had to find an active solution of the task since otherwise they were passively transported into the room frame defined punished zone. The suitability of these tasks for testing spatial abilities of rats is discussed.

Animals↗
PubMed1996

Effects of the uncompetitive NMDA receptor antagonist memantine on hippocampal long-term potentiation, short-term exploratory modulation and spatial memory in awake, freely moving rats.

Chronic treatment of adult male F-344 rats (9-12 months old) with therapeutically relevant doses of memantine (30 mg/kg/day in chow for > 8 weeks) increased the maintenance of long-term potentiation of field excitatory postsynaptic potentials from perforant path-granule cell hippocampal synapses recorded in the fascia dentata in vivo. In contrast, there was no effect of memantine on baseline synaptic responses or population spikes. Likewise, short-term exploratory modulation of these hippocampal evoked responses was not different between memantine-treated and control rats. Both groups of rats were able to learn the spatial version of the Morris water task equally well, but the memantine-treated group showed a strong tendency to show more selective spatial search patterns in the training quadrant of the water pool during a final probe trial. As such, these studies provide the first electrophysiological evidence that memantine can increase the durability of synaptic plasticity and provide preclinical confirmation of the cognitive improvement seen with memantine in the treatment of demented patients.

Animals↗
PubMed2004

Hippocampal protein-protein interactions in spatial memory.

Memory consolidation in mammalian brain is accompanied by widespread reorganization of synaptic contacts and dendritic structure. Understanding of the protein-protein interactions that underlie these structural changes has been hampered by the difficulty of studying protein-protein interactions produced in vivo by signaling, learning, and other physiological responses using current methodologies. Using a novel technique that separates interacting proteins from noninteracting proteins on the basis of their protein-target affinity, we identified 16 proteins for which protein-target binding is altered in vivo by spatial learning, including stathmin, complexin I, 14-3-3, and several structural proteins including F-actin capping protein, tubulin, GFAP, and actin. Interactions between complexin and its targets (p25alpha and Drac1-like protein) and the interaction between CapZ and tubulin were calcium-dependent. The preponderance of structural proteins and proteins involved in synapse formation and reorganization of growth cones among proteins undergoing memory-specific changes in protein-protein interactions suggests that synaptic structural reorganization is a predominant feature of the consolidation phase of memory.

Adaptor Proteins, Vesicular Transport↗
PubMed2005

Spatial memory and saccadic targeting in a natural task.

Previous work on transsaccadic memory and change blindness suggests that only a small part of the information in the visual scene is retained following a change in eye position. However, some visual representation across different fixation positions seems necessary to guide body movements. To understand what information is retained across gaze positions, it seems necessary to consider the functional demands of vision in ordinary behavior. We therefore examined eye and hand movements in a naturalistic task, where subjects copied a toy model in a virtual environment. Saccadic targeting performance was examined to see if subjects took advantage of regularities in the environment. During the first trials the spatial arrangement of the pieces used to copy the model was kept stable. In subsequent trials this arrangement was changed randomly every time the subject looked away. Results showed that about 20% of saccades went either directly to the location of the next component to be copied or to its old location before the change. There was also a significant increase in the total number of fixations required to locate a piece after a change, which could be accounted for by the corrective movements required after fixating the (incorrect) old location. These results support the idea that a detailed representation of the spatial structure of the environment is typically retained across fixations and used to guide eye movements.

Adult↗
PubMed1999

Effect of a novel prolyl endopeptidase inhibitor, JTP-4819, on spatial memory and on cholinergic and peptidergic neurons in rats with ibotenate-induced lesions of the nucleus basalis magnocellularis.

We conducted behavioral and neurochemical studies of a novel prolyl endopeptidase inhibitor, (S)2-[[(S)-2-(hydroxyacetyl)-1pyrrolidinyl]carbonyl]-N-(phenylmeth yl)-1-pyrrolidine-carboxamide (JTP-4819), in rats with lesions of the nucleus basalis magnocellularis (NBM-lesioned rats) induced by ibotenate. Administration of JTP-4819 (1 and 3 mg/kg, p.o.), on and after the 8th day, significantly shortened the escape latency in the Morris water maze as compared to the vehicle-treated group. JTP-4819 also significantly increased the path length in the quadrant with the platform removed in the spatial probe trial. Neurochemical studies of brains removed after the Morris water maze task showed that choline acetyltransferase activity in the cerebral cortex, but not the hippocampus, was significantly reduced by NBM lesioning, while there were no changes of muscarinic M1 receptor binding activity detected using [3H]pirenzepine. JTP-4819 had almost no effect on these cholinergic parameters in NBM-lesioned rats. Substance P-like immunoreactivity (LI), thyrotropin-releasing hormone (TRH)-LI, and arginine-vasopressin-LI were not significantly changed in the cerebral cortex and hippocampus of NBM-lesioned rats as compared to sham-operated rats. However, these neuropeptide levels were significantly increased in both brain regions by repeated administration of JTP-4819 (1, 3 and/or 10 mg/kg, p.o.). These results suggest that JTP-4819 ameliorated memory impairment due to NBM lesioning by potentiating SP, TRH and AVPergic neurons secondary to PEP inhibition.

Animals↗