Radial Maze Performance Research Articles

Involvement of hippocampal metabotropic glutamate receptors in radial maze performance

We investigated the role of hippocampal metabotropic glutamate receptors in spatial learning and memory, using an eight-arm radial maze task. (S)-4-Carboxyphenylglycine, a group I metabotropic glutamate receptor antagonist, or trans-(+/-)-1-amino-(1S,3R)-cyclopentanedicarboxylic acid, a broad-spectrum metabotropic glutamate receptor agonist, was administered into the dorsal hippocampus after rats had acquired the task. Both of these agents significantly impaired radial maze performance, suggesting a functional importance of hippocampal metabotropic glutamate receptors in spatial working memory.

Behavioral consequences of ovarian atrophy and estrogen replacement in the APPswe mouse

Cognitive performance was evaluated in a longitudinal study of APPswe2576 transgenic mice (APP) and a wildtype (WT) comparison group. Subgroups of the APP mice were treated with the ovarian toxicant 4-vinylcyclo-hexene diepoxide (VCD) at 60–75 days of age to induce ovarian atrophy and/or given estrogen (estradiol, 4 μg/day) continuously by pellet from 76 days of age. APP mice had a generally poorer radial maze performance than WT at 4.5, 7.5, 10.5 and 15 months of age. In separate tests, APP mice had a slight motor impairment, higher incidence of homecage stereotypy, hyperactivity in an open field and reduced object exploration relative to the WT group. Ovarian atrophy led to better maze performance at 7.5 months. The effect of estrogen on maze performance with aging could not be effectively evaluated due to poor survival (30%) of these mice. No effects of ovarian atrophy or estrogen treatment were identified for amyloid-beta accumulation or plaque formation at 15 months. Long-term longitudinal studies in animal models are needed to explore the consequences of menopause and hormone replacement on Alzheimer's disease, but they are complicated by considerations of survival, pre-aging deficits, testing experience and selection of appropriate estrogen treatment levels.

Role of hippocampal H 1 receptors in radial maze performance and hippocampal theta activity in rats

Histamine H 1 antagonists impaired the spatial memory performance. On the other hand, it is well recognized that the hippocampal theta rhythm plays a critical role in spatial memory. However, little work has been done the effect of H 1 antagonists on the hippocampal theta rhythm which was associated with the memory performance. We investigated the effect of pyrilamine, a selective H 1 receptor antagonist, on spatial memory performance as well as hippocampal theta rhythm during the memory task in rats. Effect of pyrilamine on spatial memory was measured using eight-arm radial maze with four arms baited. Hippocampal theta rhythm during the radial maze task was recorded with a polygraph system with a telemetric technique. Intraperitoneal injection of pyrilamine resulted in impairments of both reference and working memory on the radial maze task. The working memory deficit induced by pyrilamine was antagonized by the intrahippocampal injection of histamine and 6-[2-(4-imidazolyl)ethylamino]- N-(4-trifluoromethylphenyl)heptanecarboxamide (HTMT), a histamine H 1 agonist. Intraperitoneal injection of pyrilamine decreased the hippocampal theta power at a dose that impaired reference and working memory. This effect was antagonized by the intrahippocampal injection of histamine and HTMT at a dose that ameliorated the working memory deficit. Intrahippocampal injection of pyrilamine impaired working memory and simultaneously decreased the hippocampal theta power. These results suggest that: (i) the hippocampal H 1 receptors play an important role in the working memory processes on the radial maze performance and (ii) the decrease in the hippocampal theta power is associated with the working memory deficit induced by the blocking of H 1 receptors.

Frontal cortical α7 and α4β2 nicotinic acetylcholine receptors in working and reference memory

The α7 and α4β2 nicotinic acetylcholine receptor (nAchR) subtypes have been shown to be involved in memory. It is also known that losses of frontal cortical nAchRs are correlated to declining memory function in Alzheimer's disease, but the subtype-specific role of frontal cortical nAchRs in memory has not been well characterized. Hence, we sought to understand the role of frontal cortical α7 and α4β2 nAchR subtypes in both working and reference memory by observing the effects of subtype specific agonists and antagonists on radial arm maze performance. It was found that α7 nAchRs in the frontal cortex are involved in working and reference memory, while α4β2 nAchRs are only involved in working memory. Throughout the study, drug treatments did not affect motor functionality in the animals. Our data thus sheds further light on the frontal cortex as an important anatomical locus for nAchR-mediated memory function in the brain, and highlights the differing role of α7 and α4β2 nAchRs in long and short term memory.

Effect of Polygala tenuifolia Root Extract on Scopolamine-Induced Impairment of Rat Spatial Cognition in an Eight-Arm Radial Maze Task

The effects of Polygala tenuifolia root fractions and the acyl groups of its constituents on the retrieval process of spatial cognition in rats were studied using an eight-arm radial maze task. Oral administration of a precipitate fraction (PTB) obtained by concentration of the n-BuOH-soluble portion from the extract of the roots significantly decreased the number of total errors (TEs) and that of working memory errors (WMEs) at doses of 100 mg/kg and 200 mg/kg. However, it caused no significant decrease in the number of reference memory errors (RMEs). In addition, the saponin-rich fraction (PTBM) obtained by purification of PTB also showed significant decreases in TEs and WMEs at a dose of 100 mg/kg. Among the cinnamic acid derivatives present as the acyl groups in the P. tenuifolia constituents, sinapic acid (SNPA) significantly decreased TEs and WMEs at doses of 10 to 100 mg/kg. These results indicated that P. tenuifolia extracts, PTB and PTBM, and SNPA had a beneficial effect on the memory impairment induced by dysfunction of the cholinergic system in the brain. The memory improvement in the scopolamine-induced memory impairment seen in the radial maze performance was due to improvement in the short-term memory. A contribution of some constituents other than SNPA to the memory improvement was also suggested.

Effect of Histamine on Muscimol-Induced Working Memory Deficits in Radial Maze Performance

We investigated the participation of γ-aminobutyric acid (GABA) neurons of the medial septal area in eight-arm radial maze performance in rats. The intra-septal injection of muscimol, a GABAA agonist, caused an increase in total error and working memory error. On the other hand, no significant effect was observed with reference memory error. Donepezil and tacrine (cholinesterase inhibitors) antagonized the muscimol-induced spatial memory deficits. Histidine (1500 mg/kg, i.p.) also improved the total error and working memory error induced by muscimol. At this dose, histidine caused a significant increase in the histamine content of the cortex, hippocampus, and hypothalamus in rats. In addition, the intra-hippocampal injection of histamine also antagonized muscimol-induced spatial memory deficits. The practical conclusion is that the GABAA receptor of the medial septal area plays an important role in working memory, and also, the disturbance of working memory induced by muscimol is mediated not only by cholinergic but also by histaminergic systems in the spatial memory of rats.

Proactive interference on the radial arm maze performance of zebrafish

Ten zebrafish (Danio rerio) were tested in an aquatic version of the eight-arm radial maze by means of a forced- and free-choice procedure, which could not be solved using a stereotypic response pattern. After training once a day for 60 days, the fish achieved a correct-choice ratio of about 60%, significantly higher than the chance level (41.38%). Following the acquisition training, the fish received two trials a day to test effects of the length of inter-trial intervals on this maze performance. The choice accuracy for the second trials was significantly lower when the inter-trial intervals were 3 min than when they were 60 min. These results suggest that zebrafish can learn a radial-arm maze task to some extent, and that increasing the length of inter-trial intervals alleviates proactive interference on the maze performance.

Ginkgo biloba extract improves spatial memory in rats mainly but not exclusively via a histaminergic mechanism

In order to clarify the mechanism of Ginkgo biloba extract (GBE) on learning and memory, we studied the effect of GBE on spatial memory deficits induced by diphenhydramine, pyrilamine and scopolamine using the eight-arm radial maze performance of rats, in comparison with donepezil. Total error (TE), reference memory error (RME) and working memory error (WME) were used as indices of spatial memory deficits. Both GBE and donepezil caused a potent antagonistic effect on the increase in TE, RME and WME induced by diphenhydramine. GBE and donepezil also antagonized scopolamine-induced spatial memory deficits. Although the antagonistic effect of GBE on pyrilamine-induced spatial memory deficits was weak, a significant difference was observed with TE and WME. However, donepezil caused no antagonistic effect on pyrilamine-induced memory deficits. From these findings, we concluded that the effects of GBE are mainly contributable to cholinergic activity and perhaps partly due to a histaminergic mechanism.

Omega-3 fatty acids and rodent behavior

This paper reviews the role of the n-3 fatty acids in the regulation of cognitive functions, locomotor and exploratory activity and emotional status in rodents. There are disparate data on the performance of n-3 fatty acid deficient animals in the open field test and elevated plus maze. Results obtained in our laboratory indicated slower habituation to the open field in deficient mice, which affects total locomotor and exploratory parameters. We also observed no change in plus maze performance of deficient mice under low-stress but elevated anxiety under high-stress conditions. There is some evidence of elevated aggression and increased immobility time in the forced swimming test caused by n-3 fatty acid deficiency in rodents. Effects of n-3 fatty acid deficiency and supplementation on learning in several tests such as the Morris water maze, two odor olfactory discriminations, radial arm maze performance and avoidance tasks are reviewed in detail. There is some evidence of an enhanced vulnerability to stress of n-3 fatty acid deficient animals and this factor can influence performance in a variety of tests. Thus, behavioral tasks that involve a higher level of stress may better differentiate behavioral effects related to brain docosahexaenoic acid (DHA) status. It is suggested that a fruitful area for future investigations of functional alterations related to brain DHA status will be the delineation of the factors underlying changes in performance in behavioral tasks. The possible role of non-cognitive factors like emotionality and attention in the impaired performance of n-3 fatty acid deficient animals also requires further investigation.

Deglycosylated Anti-Amyloid-β Antibodies Eliminate Cognitive Deficits and Reduce Parenchymal Amyloid with Minimal Vascular Consequences in Aged Amyloid Precursor Protein Transgenic Mice

Systemic administration of anti-amyloid-beta (Abeta) antibodies results in reduced parenchymal amyloid but increased vascular amyloid and microhemorrhage in amyloid precursor protein (APP) transgenic mice. Here, we evaluate the effects of reducing effector interactions of the antibody via deglycosylation. Mice aged 20 months were treated weekly for 4 months and tested behaviorally before they were killed. APP transgenic mice receiving either anti-Abeta (2H6) or deglycosylated anti-Abeta (de-2H6) showed significant improvement in radial arm water maze performance compared with mice receiving a control antibody. Both groups receiving anti-Abeta antibodies showed significant reductions in total Abeta immunochemistry and Congo red. Significantly fewer vascular amyloid deposits and microhemorrhages were observed in mice administered the de-2H6 antibody compared with those receiving unmodified 2H6 antibody. Deglycosylated anti-Abeta antibodies may be preferable to unmodified IgG because they retain the cognition-enhancing and amyloid-reducing properties of anti-Abeta immunotherapy, while greatly attenuating the increased vascular amyloid deposition and microhemorrhage observed with unmodified IgG.

Effects of Ginkgo biloba administered after spatial learning on water maze and radial arm maze performance in young adult rats

Ginkgo biloba is reported to improve learning and memory in animals. However, many studies do not directly test the effects of Ginkgo on memory because the drug is administered during the learning phase of the experiments. In this study, we examined the effect of 10 mg/kg, 20 mg/kg, or 40 mg/kg G. biloba extract on spatial memory by administering the drug in the interval between training and testing. Rats were tested for long-term reference memory retention in the radial arm maze and in the Morris water maze during daily probe trials in which the hidden platform was removed. G. biloba had no effect on reference memory in either the water maze or radial arm maze. To test short-term working spatial memory using the radial arm maze, animals were removed after receiving the reward from 4 of the 8 arms and were returned to complete the maze 2 h later. While Ginkgo had no effect on working memory, over time animals exposed to Ginkgo learned task better than control animals. Thus, Ginkgo appears to enhance neither short-term working memory nor long-term reference memory, but it may promote learning of spatial information.

Wistar rats with high versus low rearing activity differ in radial maze performance

Substantial work has shown that rats although identical in stock, sex, age, and housing conditions can differ considerably in terms of behavior and physiology. Such individual differences, which can be detected by specific behavioral screening tests, are rather stable, that is, they probably reflect a behavioral disposition or trait. Here, we asked whether and how such differences might affect performance in a task of spatial learning and memory, the radial maze. As in our previous work, we used the degree of rearing activity in a novel open field to assign male adult outbred Wistar rats into those with high versus low rearing activity (HRA/LRA rats). They were then tested in a plus-maze for possible differences in anxiety-related behavior. Finally, and most importantly, they were food deprived and underwent maze training using an 8-arm radial maze with four non-baited and four baited arms. One of these arms consistently contained a larger bait size than the other three. In the open field, HRA rats not only showed more rearing behavior, but also more locomotor activity than LRA rats. In the plus-maze, HRA rats again showed more locomotion, but did not differ in open arm time or percentage of open arm entries, that is, conventional measures of anxiety-related behavior. In the radial maze, HRA rats consistently needed less time to consume all pellets than LRA rats, which was due to faster locomotion on the arms and less time spent at the food pits (especially in baited arms) of HRA rats. During the initial days of training, they were also more efficient in obtaining all food pellets available. Furthermore, HRA rats visited more arms and made relatively less reference memory errors than LRA rats. This allowed them to forage food quickly, but was paralleled by more working memory errors than in LRA rats. In general, working memory errors were more frequent in the arm with the large bait size, but there were no indications that HRA and LRA rats responded differently dependent on reward size. Finally, LRA rats lost slightly more weight than HRA rats during the period of food deprivation. These results are discussed with respect to the role of cognitive and motivational mechanisms, which as subject-inherent factors can contribute substantially to inter-individual variability in the radial maze.

Spatial navigation in complex and radial mazes in APP23 animals and neurotrophin signaling as a biological marker of early impairment

Impairment of hippocampal function precedes frontal and parietal cortex impairment in human Alzheimer's disease (AD). Neurotrophins are critical for behavioral performance and neuronal survival in AD. We used complex and radial mazes to assess spatial orientation and learning in wild-type and B6-Tg(ThylAPP)23Sdz (APP23) animals, a transgenic mouse model of AD. We also assessed brain content of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3). Performance was alike in wild-type and APP23 animals in the radial maze. In contrast, performance in the complex maze was better in wild-type than APP23 animals. Contrary to the wild-type, hippocampal BDNF levels decreased on training in APP23 animals. Hippocampal and frontal cortex NGF levels in APP23 animals correlated with the time to solve the complex maze, but correlated inversely with escape time in wild-type animals. NT-3 levels were alike in wild-type and APP23 animals and were unchanged even after training. Both types of mazes depend on hippocampal integrity to some extent. However, according to the cognitive mapping theory of spatial learning, the complex maze because of the increased complexity of the environment most likely depends more strongly on preserved hippocampal function than the radial maze in the working memory configuration applied here. Greater impairment in complex maze performance than in radial maze performance thus resembles the predominant affliction of the loss of hippocampal function in human AD. NGF and BDNF levels on maze learning are different in wild-type and transgenic animals, indicating that biological markers of AD may be altered on challenge even though equilibrium levels are alike.

Post insult enriched housing improves the 8-arm radial maze performance but not the Morris water maze task in ventral subicular lesioned rats

The present study attempted to evaluate the efficacy of enriched housing conditions in promoting behavioral recovery following subicular lesion. Rats with bilateral ibotenic acid lesions of ventral subiculum were exposed to either enriched housing conditions or standard housing for 6 h daily for 10 days. The performance of the lesioned rats reared in standard housing conditions was severely impaired in both 8-arm radial maze and water maze tasks. Lesioned rats exposed to enriched housing showed behavioral recovery in the 8-arm radial maze but not in the water maze. Our study suggests the possibility that recovery may be based on the functional demand of spatial tasks and may require more appropriate environmental stimulation.

EFFECT OF SEED COAT EXTRACT FROM BLACK SOYBEANS ON RADIAL MAZE PERFORMANCE IN RATS

1. In the present study, we tested the effect of seed coat extract from black soybeans on eight-arm radial maze performance in rats. 2. Rats were fed a diet containing 5% seed coat extract from black soybeans or a normal diet for 40 days. 3. One week after the start of feeding, rats were tested for learning ability related to two types of memory, reference memory and working memory, with a partially (four of eight) baited eight-arm radial maze. 4. A significant decrease in the total number of errors was observed 30 (mean value of five trials of 26-30 days) and 35 days (30-35 days) after the intake of the diet containing seed coat extract compared with the control group. In addition, the mean number of days taken to reach this criterion was significantly decreased after the intake of the diet containing the seed coat extract. 5. The number of reference memory errors was significantly decreased 30 and 35 days after the intake of the diet containing seed coat extract. However, no significant decrease was observed in the number of working memory errors. 6. From these results, it is concluded that the intake of seed coat extract from black soybeans effectively enhances memory and learning ability, especially long-term memory, in rats.

Effects of social and physical enrichment on open field activity differ in male and female Sprague–Dawley rats

Environmental enrichment affects performance of neurologically intact organisms and facilitates recovery of function following CNS injury. Only, a few recent studies have examined the extent to which physical versus social aspects of enriched environments separately contribute to superior performance [Pietropaolo S, Branchi I, Cirulli F, Chiarotti F, Aloe L, Alleva E. Long-term effects of the periadolescent environment on exploratory activity and aggressive behavior in mice: social vs. physical enrichment. Physiol Behav 2004;81:443–53; Schrijver NC, Bahr NI, Weiss IC, Wurbel H. Dissociable effects of isolation rearing and environmental enrichment on exploration, spatial learning and HPA activity in adult rats. Pharmacol Biochem Behav 2002;73:209–24] or the extent to which male and females differ in their response to enrichment [Bardo MT, Kiebaur JE, Valone JM, Deaton C. Environmental enrichment decreases intravenous self-administration of amphetamine in male and female rats. Psychopharm 2001;155:278–84; Daniel JM, Roberts S, Dohanich G. Effects of ovarian hormones and environment on radial maze and water maze performance of female rats. Physiol Behav 1999;66:11–20]. The current experiment examined the separate and combined effects of social enrichment (SE) and physical enrichment (PE) on locomotor activity of male and female Sprague–Dawley rats to determine what aspect of enrichment had the greatest effect to alter activity and to determine whether there were sex differences in these effects. Habituation in the open field was used as an index of simple information-processing and refers to the decrease in activity over time that occurs as an animal becomes acclimated to its environment. Faster habituation indicates greater information-processing. The major findings from the current study were: (1) social enrichment has the greatest effect to improve performance (i.e., increased habituation) for both males and females and (2) the effects of enrichment overall generally appear to be greater for males than for females.

Dissociable memory effects after medial thalamus lesions in the rat

Variable neuropathology in cases of diencephalic amnesia has led to uncertainty in identifying key thalamic nuclei and their potential role in learning and memory. Based on the principal neural connections of the medial thalamus, the current study tested the hypothesis that different aggregates of thalamic nuclei contribute to separate memory systems. Lesions of the anterior thalamic aggregate (AT), which comprises the anterodorsal, anteromedial and anteroventral nuclei produced substantial deficits in both working and reference spatial memory in a radial arm maze task in rats, supporting the view that the AT is an integral part of a hippocampal memory system. Lesions to the lateral thalamic aggregate (LT), which comprises the intralaminar nuclei (centrolateral, paracentral and rostral central medial nuclei) and lateral mediodorsal thalamic nuclei (lateral and paralamellar nuclei) produced a mild working memory impairment only, while lesions to the posteromedial thalamic aggregate (MT), which comprises the central and medial mediodorsal thalamic nuclei and the intermediodorsal nucleus had no effect on radial arm maze performance. In contrast, only MT lesions impaired learning associated with memory for reward value, consistent with the idea that the MT contributes to an amygdala memory system. Compared with chance discrimination, the control and AT groups, but not MT or LT groups, showed evidence for temporal order memory for two recently presented objects; all groups showed intact object recognition for novel vs. familiar objects. These new dissociations show that different medial thalamic aggregates participate in multiple memory systems and reinforce the idea that memory deficits in diencephalic amnesics may vary as a function of the relative involvement of different thalamic regions.

Prenatal exposure to alcohol does not affect radial maze learning and hippocampal mossy fiber sizes in three inbred strains of mouse

BackgroundThe aim of this study was to investigate the effects of prenatal alcohol exposure on radial-maze learning and hippocampal neuroanatomy, particularly the sizes of the intra- and infrapyramidal mossy fiber (IIPMF) terminal fields, in three inbred strains of mice (C57BL/6J, BALB/cJ, and DBA/2J).ResultsAlthough we anticipated a modification of both learning and IIPMF sizes, no such effects were detected. Prenatal alcohol exposure did, however, interfere with reproduction in C57BL/6J animals and decrease body and brain weight (in interaction with the genotype) at adult age.ConclusionPrenatal alcohol exposure influenced neither radial maze performance nor the sizes of the IIPMF terminal fields. We believe that future research should be pointed either at different targets when using mouse models for Fetal Alcohol Syndrome (e.g. more complicated behavioral paradigms, different hippocampal substructures, or other brain structures) or involve different animal models.

Whole-body exposure to 2.45 GHz electromagnetic fields does not alter 12-arm radial-maze with reduced access to spatial cues in rats

Lai et al. [Lai H, Horita A, Guy AW. Microwave irradiation affects radial-arm maze performance in the rat. Bioelectromagnetics 1994;15(2):95–104] reported that exposure of rats to pulsed 2.45 GHz microwaves altered maze performance. Their maze was bordered by 20 cm high opaque walls. Using a maze test based on unrestrained access to spatial cues (no walls), we could not replicate this result [Cassel JC, Cosquer B, Galani R, Kuster N. Whole-body exposure to 2.45 GHz electromagnetic fields does not alter radial-maze performance in rats. Behav Brain Res 2004;155:37–43]. Here, we attempted another replication using a maze apparatus bordered by 30 cm high opaque walls. Performance of exposed rats was normal. These results show that microwave exposure as used herein does not alter spatial working memory, when access to spatial cues is reduced.

Behavioral and neurochemical phenotyping of Homer1 mutant mice: possible relevance to schizophrenia

Homer proteins are involved in the functional assembly of postsynaptic density proteins at glutamatergic synapses and are implicated in learning, memory and drug addiction. Here, we report that Homer1-knockout (Homer1-KO) mice exhibit behavioral and neurochemical abnormalities that are consistent with the animal models of schizophrenia. Relative to wild-type mice, Homer1-KO mice exhibited deficits in radial arm maze performance, impaired prepulse inhibition, enhanced 'behavioral despair', increased anxiety in a novel objects test, enhanced reactivity to novel environments, decreased instrumental responding for sucrose and enhanced MK-801- and methamphetamine-stimulated motor behavior. No-net-flux in vivo microdialysis revealed a decrease in extracellular glutamate content in the nucleus accumbens and an increase in the prefrontal cortex. Moreover, in Homer1-KO mice, cocaine did not stimulate a rise in frontal cortex extracellular glutamate levels, suggesting hypofrontality. These behavioral and neurochemical data derived from Homer1 mutant mice are consistent with the recent association of schizophrenia with a single-nucleotide polymorphism in the Homer1 gene and suggest that the regulation of extracellular levels of glutamate within limbo-corticostriatal structures by Homer1 gene products may be involved in the pathogenesis of this neuropsychiatric disorder.