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At least 1,693 records · Page 94Linked to original sources
PubMed2003

Effects of head-slaved navigation and the use of teleports on spatial orientation in virtual environments.

The type of navigation interface in a virtual environment (VE)--head slaved or indirect--determines whether or not proprioceptive feedback stimuli are present during movement. In addition, teleports can be used, which do not provide continuous movement but, rather, discontinuously displace the viewpoint over large distances. A two-part experiment was performed. The first part investigated whether head-slaved navigation provides an advantage for spatial learning in a VE. The second part investigated the role of anticipation when using teleports. The results showed that head-slaved navigation has an advantage over indirect navigation for the acquisition of spatial knowledge in a VE. Anticipating the destination of the teleport prevented disorientation after the displacement to a great extent but not completely. The time that was needed for anticipation increased if the teleport involved a rotation of the viewing direction. This research shows the potential added value of using a head-slaved navigation interface--for example, when using VE for training purposes--and provides practical guidelines for the use of teleports in VE applications.

Adolescent↗
PubMed1993

Hippocampal morphology and spatially related behavior in Long-Evans and CFY rats.

Behavioral responses to novelty in an open field and spatial learning in a radial maze with four arms out of eight reinforced were tested in male and female CFY and Long-Evans rats. Subsequently, the sizes of the total hippocampi and of various hippocampal cell layers and terminal fields at the midseptotemporal level were measured in Timm-stained sections. No strain differences were found in the open field (except for defecation). In the radial maze, Long-Evans rats showed better spatial reference memory capabilities than rats of the CFY strain. The relative sizes of the intra- and infrapyramidal mossy fiber (IIP-MF) projections did not differ between the strains. Within the more variable CFY strain, a positive correlation between the size of the IIP-MF projection and radial maze performance was found. The absolute sizes of the entire hippocampi and all hippocampal layers at the midseptotemporal level were larger in the CFY strain. The size of the suprapyramidal mossy fiber projection was related to the number of granule cells and to the ratio between granule and CA3 pyramidal cells. In contrast, the size of the IIP-MF projection did not correlate with either of these variables. The results indicate that the size of the mossy fiber projection may be determined mainly by the available postsynaptic surface on the dendrites of CA3 pyramidal neurons. Furthermore, an increased number of granule cells and their larger projection to the apical dendrites of pyramidal neurons does not appear to result in physiological changes with behavioral consequences.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2006

Impaired sequential egocentric and allocentric memories in forebrain-specific-NMDA receptor knock-out mice during a new task dissociating strategies of navigation.

The hippocampus is considered to play a role in allocentric but not in egocentric spatial learning. How does this view fit with the emerging evidence that the hippocampus and possibly related cortical areas are necessary for episodic-like memory, i.e., in all situations in which events need to be spatially or sequentially organized? Are NMDA receptor-dependent mechanisms crucial for the acquisition of spatiotemporal relationships? To address this issue, we used knock-out (KO) mice lacking hippocampal CA1 NMDA receptors and presenting a reduction of these receptors in the deep cortical layers (NR1-KO mice). A new task (the starmaze) was designed, allowing us to distinguish allocentric and sequential-egocentric memories. NR1-KO mice were impaired in acquiring both types of memory. Our findings suggest that memories composed of multiple spatiotemporal events require intact NMDA receptors-dependent mechanisms in CA1 and possibly in the deep cortical layers.

Animals↗
PubMed2002

Allopregnanolone inhibits learning in the Morris water maze.

The progesterone metabolite allopregnanolone (3alpha-OH-5alpha-pregnane-20-one) inhibits neural functions, enhancing the GABA induced GABA(A) receptor activation. This effect is benzodiazepine like and benzodiazepines are known to impair memory. Acute effects of allopregnanolone on the hippocampus dependent spatial learning in the Morris water maze have not been studied. Adult male Wistar rats where injected (i.v.) with allopregnanolone (2 mg/kg), or vehicle, daily for 11 days. At 8 or 20 min after each injection, studies of place navigation were performed in the Morris water maze. Allopregnanolone concentrations in plasma and in nine different brain areas where analyzed by radioimmunoassay. The latency to find the platform was increased 8 min after the allopregnanolone injection, while normal learning was seen after 20 min. Swim speed did not differ between groups. A higher number of rats were swimming close to the pool wall (thigmotaxis) in the 8 min allopregnanolone group compared to the other groups. Allopregnanolone concentrations in the brain tissue at 8 min were 1.5 to 2.5 times higher then at 20 min after the allopregnanolone injections. After vehicle injections the brain concentrations of allopregnanolone were at control levels. Plasma concentrations of allopregnanolone followed the same pattern as in the brain, with the exception of an increase 8 min after vehicle injections. The natural progesterone metabolite allopregnanolone can inhibit learning in the Morris water maze, an effect not caused by motor impairment. The learning impairment might be due to a combination of changed swimming behavior and difficulties in navigation.

Anesthetics↗
PubMed2000

NMDA receptor antagonism in the basolateral amygdala blocks enhancement of inhibitory avoidance learning in previously trained rats.

Extensive evidence suggests that N-methyl-D-aspartate (NMDA) glutamate receptor channels in the amygdala are involved in fear-motivated learning, and infusion of NMDA receptor antagonists into the amygdala blocks memory of fear-motivated tasks. Recent studies have shown that previous training can prevent the amnestic effects of NMDA receptor antagonists on spatial learning. In the present study, we evaluated whether infusion of the NMDA antagonist D,L-2-amino-5-phosphonopentanoic acid (AP5) into the basolateral nucleus of the amygdala (BLA) impairs reinforcement of inhibitory avoidance learning in rats given previous training. Adult male Wistar rats (220-310 g) were bilaterally implanted under thionembutal anesthesia (30 mg/kg, i.p.) with 9.0-mm guide cannulae aimed 1.0 mm above the BLA. Infusion of AP5 (5.0 microg) 10 min prior to training in a step-down inhibitory avoidance task (0.4 mA footshock) blocked retention measured 24 h after training. When infused 10 min prior to a second training session in animals given previous training (0.2 mA footshock), AP5 blocked the enhancement of retention induced by the second training. Control experiments showed that the effects were not due to alterations in motor activity or footshock sensitivity. The results suggest that NMDA receptors in the basolateral amygdala are involved in both formation of memory for inhibitory avoidance and enhancement of retention in rats given previous training.

2-Amino-5-phosphonovalerate↗
PubMed2000

Learning performances, brain NGF distribution and NPY levels in transgenic mice expressing TNF-alpha.

Tumor necrosis factor-alpha (TNF-alpha) is a cytokine involved in a variety of neurobiological activities including changing behavior and regulation of both neurotrophin and neuropeptide levels. In this study we used two lines of transgenic mice overexpressing brain TNF-alpha characterized by neurological deficits (line Tg6074) or phenotypically normal (line TgK3). We analyzed whether or not impairments in learning and memory processes due to TNF-alpha overexpression were associated with changes in endogenous brain NGF, NPY and beta-amyloid. The results indicate that full TNF-alpha transgene expression disrupted the learning capabilities of transgenic mice (both Tg6074 and TgK3). NGF decreased in the hippocampus of both transgenic mice whereas hippocampal NPY slightly potentiated in Tg6074. The decrease in NGF is correlated with deficits in spatial learning and memory whereas inflammation in the brain of Tg6074 could be responsible of the hippocampal increase in NPY. As a whole, these results show that transgenic mice overexpressing TNF-alpha in the brain represent a useful model for studying neuronal degeneration and brain inflammatory processes.

Amyloid beta-Peptides↗
PubMed2004

Beta-sheet breaker peptide prevents Abeta-induced spatial memory impairments with partial reduction of amyloid deposits.

Current evidence supports the notion that beta-amyloid deposits or Abeta intermediates may be responsible for the pathogenesis in Alzheimer's disease (AD) patients. In the present work, we have assessed the neuroprotective effect of the chronic intraperitoneal administration of a five-amino-acid beta-sheet breaker peptide (iAbeta5p) on the rat behavioral deficit induced by the intrahippocampal Abeta-fibrils injection. At 1 month after the injection, animals showed a partial reduction of the amyloid deposits formed and a decreased astrocytic response around the injection site. More importantly, we report that following the iAbeta5p treatment, hippocampal-dependent spatial learning paradigms, including the standard Morris water maze and a working memory analysis, showed a significant prevention from impairments induced by Abeta deposits in the dorsal hippocampus. Thus, it is possible that a noninvasive treatment such as the one presented here with beta-sheet breaker peptides may be used as a potential therapy for AD patients.

Alzheimer Disease↗
PubMedDate not supplied

Contrasting hippocampal and perirhinal cortex function using immediate early gene imaging.

The perirhinal cortex and hippocampus have close anatomical links, and it might, therefore, be predicted that they have close, interlinked roles in memory. Lesion studies have, however, often failed to support this prediction, providing dissociations and double dissociations between the two regions on tests of object recognition and spatial memory. In a series of rat studies we have compared these two regions using the expression of the immediate early gene c-fos as a marker of neuronal activity. This gene imaging approach makes it possible to assess the relative involvement of different brain regions and avoids many of the limitations of the lesion approach. A very consistent pattern of results was found as the various hippocampal subfields but not the perirhinal cortex show increased c-fos activity following tests of spatial learning. In contrast, the perirhinal cortex but none of the hippocampal subfields show increased c-fos activity when presented with novel rather than familiar visual objects. When novel scenes are created by the spatial rearrangement of familiar objects it is the hippocampus and not the perirhinal cortex that shows c-fos changes. This double dissociation for gene expression accords with that found from lesion studies and highlights the different contributions of the perirhinal cortex and hippocampus to memory.

Animals↗
PubMed2006

Cognitive deficits in rats after forebrain cholinergic depletion are reversed by a novel NO mimetic nitrate ester.

Many conditions adversely affecting learning, memory, and cognition are associated with reductions in forebrain acetylcholine (ACh), most notably aging and Alzheimer's disease. In the current study, we demonstrate that bilateral depletion of neocortical and hippocampal ACh in rats produces deficits in a spatial learning task and in a recently described, delayed visual matching-to-sample task. Oral administration of the novel nitrate, GT1061 (4-methyl-5-(2-nitroxyethyl) thiazole HCl), and the acetylcholinesterase inhibitor, donepezil, reversed the cognitive deficits in both memory tasks in a dose-dependent manner. GT1061 was superior in the delayed matching-to-sample task. GT1061 was absorbed rapidly after oral administration, crossed the blood brain barrier, and achieved brain concentrations that were slightly higher than those found in plasma. The activity of GT1061 was NO mimetic: soluble guanylyl cyclase (sGC) was activated, but selectivity was observed for sGC in the hippocampus relative to the vasculature; and hippocampal levels of phosphorylated ERK1/2, which is a postulated intermediary in the formation of long-term memory, were increased. The beneficial effect on visual and spatial memory task performance supports the concept that stimulating the NO/sGC/cGMP signal transduction system can provide new, effective treatments for cognitive disorders. This approach may be superior to that of current drugs that attempt only to salvage the residual function of damaged cholinergic neurons.

Acetylcholine↗
PubMed1994

Grafting of nerve growth factor-producing fibroblasts reduces behavioral deficits in rats with lesions of the nucleus basalis magnocellularis.

Rats received bilateral lesions of the nucleus basalis magnocellularis by infusion of biotenic acid. Two weeks after the lesion, a suspension of genetically modified primary rat fibroblasts was grafted dorsal to the nucleus basalis magnocellularis (2 x 10(5) cells per side). The fibroblasts were either infected with the gene for human beta-nerve growth factor or Escherichia coli beta-galactosidase. The nerve growth factor-producing fibroblasts released 67 ng nerve growth factor/10(5) cells per day in vitro. Two weeks after implantation of the fibroblasts, spatial learning was tested in the Morris water-maze. Nerve growth factor-producing fibroblasts, but not beta-galactosidase-producing fibroblasts ameliorated the deficit in acquisition of the water-maze task. In addition, spatial acuity was improved to near-normal levels by the nerve growth factor-producing grafts. Choline acetyltransferase activity in cortical areas and hippocampus was not affected by the nerve growth factor-producing grafts. Both grafted groups showed a similar reduction in the level of dopamine, but not homovanillic acid or 3-methoxytyramine, in the frontal cortex. Levels of norepinephrine, epinephrine and serotonin and their metabolites in the neocortex and hippocampus were not affected by the lesion or the grafts. Nerve growth factor-producing grafts increased the size of remaining nerve growth factor-receptor (p75) immunoreactive neurons in the nucleus basalis magnocellularis by 25%. Nucleus basalis magnocellularis lesions reduced the integrated optic density of choline acetyltransferase-positive fiber staining in the ventral neocortex by 46%, but nerve growth factor-producing grafts restored this area to 86% of control. These data suggest that nerve growth factor-producing grafts can cause a marked behavioral improvement, probably through the partial restoration of the lesioned projection from nucleus basalis magnocellularis to neocortex.

Animals↗
PubMed2006

The expression of TRH, its receptors and degrading enzyme is differentially modulated in the rat limbic system during training in the Morris water maze.

TRH administration induces arousal, improves cognition, and modulates glutamatergic and cholinergic transmission in hippocampal neurons. To study the possible involvement of TRH neurons in learning and memory processes, gene expression of TRH, its receptors, and pyroglutamyl peptidase (PPII), were measured in limbic regions of water-maze trained rats. Hypothalamus and amygdala showed changes related to the task but not specific to spatial learning while in hippocampus, pro-TRH and TRH-R1 mRNA levels were specifically increased in those animals trained to find a hidden platform. Variation of TRH content and mRNA levels of pro-TRH, TRH-R1, TRH-R2 and PPII are observed in conditions known to activate TRH hypophysiotropic neurons. Changes in some of these parameters could indicate the activation of TRHergic neurons and their possible involvement in some memory related process. Male Wistar rats were immersed (10 times) for 1, 3 or 5 days in a Morris water-maze containing, or not (yoked control) a platform and sacrificed 5, 30 and 60 min after last trial. TRH content and TSH serum levels were determined by radioimmunoassay; mRNA levels of pro-TRH, TRH-R1, TRH-R2, and PPII, by RT-PCR. Exclusive changes due to spatial training were observed in posterior hippocampus of rats trained for 5 days sacrificed after 60min: decreased TRH content and increased mRNA levels of pro-TRH and TRH-R1, particularly in CA3 region (measured by in situ hybridization). The hypothalamus-pituitary axis responded in both yoked and trained animals (increasing serum TSH levels and pro-TRH expression, due to swim-stress); in the amygdala of both groups, pro-TRH expression increased while diminished that of both receptors and PPII. Differential expression of these parameters suggests involvement of TRH hippocampal neurons in memory formation processes while changes in amygdala could relate to TRH anxiolytic role. The differential modulation in anterior and posterior portions of the hippocampus is discussed.

Animals↗
PubMed2006

Fixed versus dynamic orientations in environmental learning from ground-level and aerial perspectives.

Ground-level and aerial perspectives in virtual space provide simplified conditions for investigating differences between exploratory navigation and map reading in large-scale environmental learning. General similarities and differences in ground-level and aerial encoding have been identified, but little is known about the specific characteristics that differentiate them. One such characteristic is the need to process orientation; ground-level encoding (and navigation) typically requires dynamic orientations, whereas aerial encoding (and map reading) is typically conducted in a fixed orientation. The present study investigated how this factor affected spatial processing by comparing ground-level and aerial encoding to a hybrid condition: aerial-with-turns. Experiment 1 demonstrated that scene recognition was sensitive to both perspective (ground-level or aerial) and orientation (dynamic or fixed). Experiment 2 investigated brain activation during encoding, revealing regions that were preferentially activated perspective as in previous studies (Shelton and Gabrieli in J Neurosci 22:2711-2717, 2002), but also identifying regions that were preferentially activated as a function of the presence or absence of turns. Together, these results differentiated the behavioral and brain consequences attributable to changes in orientation from those attributable to other characteristics of ground-level and aerial perspectives, providing leverage on how orientation information is processed in everyday spatial learning.

Adult↗
PubMed2004

Dopamine D3 receptor antagonists improve the learning performance in memory-impaired rats.

RATIONALE: The dopamine D3 receptor has been extensively studied in animal models of drug abuse and psychosis; however, less is known on its possible role in cognitive functions. OBJECTIVES: This study investigated the effects of different D3 antagonists and a partial agonist on spatial learning performance in a water labyrinth test. METHODS: Rats had to swim through a labyrinth system by making correct directional turns at three choice-points. The number of errors was recorded in three daily trials for 3 days. RESULTS: D3 antagonists such as the highly selective SB-277011 (24 mg/kg p.o.) and RGH-1756 (1 mg/kg p.o.), the moderately selective U-99194A (12 mg/kg s.c.) and the selective partial D3 agonist BP-897 (1 mg/kg i.p.) all significantly attenuated the learning deficit caused by FG-7142. Against scopolamine-induced amnesia, SB-277011 (24 mg/kg p.o.) was equally potent in showing protective efficacy; however, two times higher dose levels of U-99194A (24 mg/kg s.c.) and RGH-1756 (2 mg/kg p.o.) were required to attenuate the scopolamine-induced impairment. In contrast to the full antagonists, against scopolamine-induced amnesia, the partial agonist BP-897 (2 mg/kg i.p.) was inactive, even at the two times higher dose level. CONCLUSIONS: These data suggest that dopamine D3 receptor antagonists possess cognition-enhancing activity which may be of benefit in the treatment of cognitive dysfunction associated with several psychiatric disorders.

Animals↗
PubMed1987

Development of interocular equivalence in rats trained on a distal-cue navigation task.

What is learned about the visual world through one eye can be retrieved and used to guide behavior by the other eye. To study the development of this phenomenon, called interocular equivalence, we trained rats on a spatial learning task. Rats only 22 days old were able to learn this task with one eye, but they demonstrated no interocular equivalence. This capacity began to emerge when pups were 25 days old but was not robust until pups were 28 days old. That interocular equivalence emerges gradually during development suggests that the young rat, in some ways, may function as a split-brain animal.

Animals↗
PubMed1997

Memory-related changes of nitric oxide synthase activity and nitrite level in rat brain.

The changes of nitric oxide synthase (NOS) activity and nitrite level in rat brain regions after spatial learning were investigated. NOS activity was assayed by conversion of [3H]L-arginine to [3H]L-citrulline, and a sensitive fluorometric assay for quantification of nitrite was used. Compared with sham-trained rats, NOS activity and nitrite level in hippocampus and cortex, and also the nitrite level in cerebellum, was elevated significantly one day after rats had learnt a water-rewarded spatial alteration task. These results suggest a spatial memory-related changes of endogenous NO in rat brain, and support the idea that NO participates in learning and memory processes.

Animals↗
PubMed2004

Visual acuity in the water maze: sensitivity to muscarinic receptor blockade in rats and mice.

A visual acuity task performed in the water maze in rats [Behav. Brain Res. 119 (2001) 77] was used to reveal the sensitivity of the visual system to muscarinic receptor blockade. Intraperitoneal injection of 0.2 mg/kg scopolamine had no effect, but 2 mg/kg severely compromised visual acuity, but did not affect the swim strategy to solve the task. Spatial learning in a reference memory version of the water maze, however, was impaired by 0.2 mg/kg scopolamine. It was also confirmed that the same visual acuity task is applicable to C57BL6/J mice. The visual deficit induced by 2 mg/kg scopolamine was less severe compared to rats, possibly due to a change in swim strategy in the drug condition. The effect of scopolamine on spatial reference memory in mice was not tested in this study. These data suggest that it may be possible to dissociate drug-induced effects on memory from changes in sensory perception.

Analysis of Variance↗
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↗
PubMed2001

Synaptic plasticity in the hippocampus of awake C57BL/6 and DBA/2 mice: interstrain differences and parallels with behavior.

C57BL/6 mice consistently outperform DBA/2 mice in a range of hippocampal-dependent spatial learning behaviors. We recorded evoked responses from the dentate gyrus of awake, freely-moving mice and measured synaptic plasticity (LTP) and performance in a hippocampal-dependent task in individual animals from these two inbred strains. Spatial alternation tasks confirmed the behavioral divergence between the two strains, with C57BL/6 mice demonstrating more robust alternation than DBA/2 mice. Recording changes in field potentials in the dentate gyrus following three different high-frequency stimulation paradigms in the same groups of animals revealed differences in neural plasticity: both strains were able to support long-term potentiation (LTP) at perforant path synapses, but brief high-frequency stimulation induced larger and longer potentiation of the population spike in C57BL/6 than in DBA/2 mice. This greater propensity for population-spike potentiation in the strain that performed better in a hippocampal-dependent task is in accord with the different neurochemical profiles of C57BL/6 and DBA/2 mice.

Action Potentials↗