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PubMed1995

Influence of place learning on somatostatin levels in the rat brain following environmental deprivation.

We have previously reported increased somatostatin levels in the cerebral cortex of rats housed in impoverished environment and subsequently subjected to a behavioural testing procedure, consisting of open-field exposure and spatial learning. The aim of the present study was to evaluate the degree of neurochemical specificity of the activation of somatostatin neurotransmission and to examine whether the altered levels were due to learning stimulation. Adult rats, previously housed individually for 30 days, were exposed to repeated sessions of a spatial learning task (2 days or 14 days) or repeated sessions of free swimming (14 days). The training sessions of the 14 day group consisted in recurrently changed position of the platform in a learning-set paradigm. Our data showed increased somatostatin immunoreactivity, and unchanged substance P immunoreactivity in the posterior part of the cerebral cortex. However, somatostatin levels increased to a similar extent following 14 days of repeated spatial learning sessions as free swimming sessions. We conclude that the activity of the cortical somatostatin system appears to be sensitive to environmentally induced sensorimotor stimulation in general, rather than learning per se. Thus, external stimulation of early clinical dementia patients with preserved sensorimotor receptivity, in an attempt to restore cognitive function, might be associated with altered somatostatin levels.

Analysis of Variance↗
PubMed2000

Involvement of brain-derived neurotrophic factor in spatial memory formation and maintenance in a radial arm maze test in rats.

Brain-derived neurotrophic factor (BDNF) regulates both short-term synaptic functions and activity-dependent synaptic plasticity such as long-term potentiation. In the present study, we investigated the role of BDNF in the spatial reference and working memory in a radial arm maze test. The radial arm maze training resulted in a significant increase in the BDNF mRNA expression in the hippocampus, although the expression in the frontal cortex did not change. When spatial learning was inhibited by treatment with 7-nitroindazole, an inhibitor of brain nitric oxide synthase, the increase in the hippocampal BDNF mRNA did not occur. To clarify the causal relation between BDNF mRNA expression and spatial memory formation, we examined the effects of antisense BDNF treatment on spatial learning and memory. A continuous intracerebroventricular infusion of antisense BDNF oligonucleotide resulted in an impairment of spatial learning, although the sense oligonucleotide had no effect. Treatment with antisense, but not sense, BDNF oligonucleotide was associated with a significant reduction of BDNF mRNA and protein levels in the hippocampus. Furthermore, treatment with antisense BDNF oligonucleotide in rats, which had previously acquired spatial memory by an extensive training, impaired both reference and working memory. There were no differences in locomotor activity, food consumption, and body weight between the antisense and sense oligonucleotide-treated rats. These results suggest that BDNF plays an important role not only in the formation, but also in the retention and/or recall, of spatial memory.

Analysis of Variance↗
PubMed1984

Intellectual and memory impairment in moderate and heavy drinkers.

Heavy drinkers (more than 2 liters of wine per day), without clinical evidence of brain dysfunction, moderate drinkers (1 liter of wine per day) and control subjects (no more than 250 cc of wine per day) were given the Progressive Matrices test and two learning tests, one tapping verbal memory and the other spatial memory. Heavy drinkers' performance was significantly worse than that of the other groups on the Progressive Matrices test and the spatial learning test. With a more lenient method of analysis, the difference between heavy drinkers and controls on the verbal learning test and that between moderate drinkers and controls on the Progressive Matrices test were also significant. When the influence of intelligence on memory performance was partialled out by covarying memory scores for Progressive Matrices scores, all differences on the verbal learning test disappeared whereas the spatial learning test still discriminated heavy drinkers from mild drinkers and controls. The bearing of these findings on the continuum of impairment hypothesis and the right hemisphere vulnerability hypothesis is discussed.

Adult↗
PubMed1992

Effects of lesion of the inferior olivary complex by 3-acetylpyridine on learning and memory in the rat.

DA/HAN-strained male rats (pigmented rats) were submitted to two experimental tasks consisting of spatial learning (water-escape) and a passive avoidance conditioning. Both these tasks were performed by different animals. In order to destroy the inferior olivary complex, the animals were injected with 3-acetylpyridine either 9 days prior to the initial learning session or 24 h after completion of the learning task. They were retested (retrieval test) 10 days after the initial learning was achieved. Learning and retention were compared to those noted in control rats. Administration of 3-acetylpyridine before the initial learning did not prevent the spatial learning but the scores were greatly altered and the number of trials needed to reach the fixed learning criterion was much greater than in controls. However, 10 days later the animals had memorized their initial experience. Injection of 3-acetylpyridine after the initial learning session impaired memory: the animals had completely forgotten their initial learning. It can therefore be concluded that lesion of the afferent climbing fibres to the cerebellar cortex alters learning and retention of a spatial task. Such a lesion does not interfere with learning and retention of a passive avoidance conditioning, since in this condition the experimental animals injected with 3-acetylpyridine either before or after the initial learning behave similarly to controls. The effects of the inferior olivary complex lesion are obviously different according to the task to be learnt, suggesting that these two tasks do not require the integrity of the same nervous structures.

Animals↗
PubMed1994

Spatial association learning by rufous hummingbirds (Selasphorus rufus): effects of relative spacing among stimuli.

Gestalt theory predicts that when cues are spatially separated from response locations, associative learning is faster when distance between cue-response location pairs is increased. This prediction was tested with 20 rufous hummingbirds (Selasphorus rufus), which learned to select rewarding feeders signaled by a spatially separated light cue in 4 treatments in which distance between cues and feeders and between cue-feeder pairs was varied. As has been shown for other animals, the hummingbirds learned more slowly when the distance between cues and feeders was increased, and as predicted by Gestalt theory, they learned faster at a given distance when distance between cue-feeder pairs was increased. This result suggests that spatial association is influenced by the proximity of other stimuli in the visual field.

Animals↗
PubMedDate not supplied

Effects of aerosol-vapor JP-8 jet fuel on the functional observational battery, and learning and memory in the rat.

To determine whether JP-8 jet fuel affects parameters of the Functional Observational Battery (FOB), visual discrimination, or spatial learning and memory, the authors exposed groups of male Fischer Brown Norway hybrid rats for 28 d to aerosol/vapor-delivered JP-8, or to JP-8 followed by 15 min of aerosolized substance P analogue, or to sham-confined fresh room air. Behavioral testing was accomplished with the U.S. Environmental Protection Agency's Functional Observational Battery. The authors used the Morris swim task to test visual and spatial learning and memory testing. The spatial test included examination of memory for the original target location following 15 d of JP-8 exposure, as well as a 3-d new target location learning paradigm implemented the day that followed the final day of exposure. Only JP-8 exposed animals had significant weight loss by the 2nd week of exposure compared with JP-8 with substance P and control rats; this finding compares with those of prior studies of JP-8 jet fuel. Rats exposed to JP-8 with or without substance P exhibited significantly greater rearing and less grooming behavior over time than did controls during Functional Observational Battery open-field testing. Exposed rats also swam significantly faster than controls during the new target location training and testing, thus supporting the increased activity noted during Functional Observational Battery testing. There were no significant differences between the exposed and control groups' performances during acquisition, retention, or learning of the new platform location in either the visual discrimination or spatial version of the Morris swim task. The data suggest that although visual discrimination and spatial learning and memory were not disrupted by JP-8 exposure, arousal indices and activity measures were distinctly different in these animals.

Administration, Inhalation↗
PubMed2000

Effects of glucose on scopolamine-induced learning deficits in rats performing the Morris water maze task.

In order to assess the effects of glucose on drug-induced spatial learning deficits, three experiments were conducted using the Morris water maze. Scopolamine and glucose were injected ip at various stages of training. Rats of Wistar strain served as subjects. In Experiment 1, scopolamine (0.4 mg/kg) and 10, 100, or 500 mg/kg of glucose were administered every day from the start of training, and the effect on acquisition was evaluated. In Experiment 2, scopolamine and 100 or 500 mg/kg of glucose were administered after 6 days of training, and the effect on performance was assessed. In Experiment 3, scopolamine and 500 mg/kg of glucose were injected after 2 days of training, and the effect on the following trial was tested. In all experiments, scopolamine impaired acquisition/performance of the task. Glucose at 500 mg/kg showed a significant enhancing effect on acquisition regardless of scopolamine injection only when injected daily from the start of training (Experiment 1). Glucose injected after the performance has reached asymptote (Experiment 2) did not affect performance, and glucose in the middle of training showed a slight but insignificant enhancing effect (Experiment 3). These results may suggest that the effect of glucose changes as a function of the degree of learning of the spatial learning task. The possibility of task specificity of the glucose effect was also discussed in relation to the cholinergic systems and local cerebral glucose utilization.

Animals↗
PubMed2000

Consolidation of passive avoidance learning is associated with transient increases of polysialylated neurons in layer II of the rat medial temporal cortex.

Within the rat medial temporal lobe, transient modulations of neural cell adhesion molecule (NCAM) polysialylation have been observed to follow spatial learning. These have been attributed to neuroplastic events associated with the processing of information destined for long term memory consolidation. To determine if similar events are associated with avoidance learning, we investigated change in polysialylated cell number in the entorhinal, perirhinal, and piriform cortex, following acquisition of a passive avoidance task in the rat. Direct quantification of polysialylated neurons in layer II of these cortical regions revealed a significant increase in polysialylated cell frequency at 12 h following passive avoidance training. Unlike spatial learning, the increased expression of polysialylated neurons persisted for up to 24-48 h following training. In the more dorsal aspect of the perirhinal/entorhinal cortex, this increase was found to be specific to learning, as it was not observed in animals rendered amnesic with scopolamine. By contrast, change in polysialylated cell frequency in the ventral aspect of the medial temporal lobe was only partially reduced by amnesic doses of scopolamine. The persisting activation of NCAM polysialylation in the more dorsal aspects of the perirhinal and entorhinal cortex is suggested to reflect the need for more extensive synaptic alterations, as compared to those required for the consolidation of spatial learning. Moreover, the neuroplastic modulations observed in the more ventral regions of the entorhinal and perirhinal cortex appear to be a unique aspect of avoidance conditioning that reflects the activation of alternative learning strategies associated with motivational and/or contextual parameters of the task.

Animals↗
PubMed2000

Dissociation of place and cue learning by telencephalic ablation in goldfish.

This study examined the spatial strategies used by goldfish (Carassius auratus) to find a goal in a 4-arm maze and the involvement of the telencephalon in this spatial learning. Intact and telencephalon-ablated goldfish were trained to find food in an arm placed in a constant room location and signaled by a local visual cue (mixed place-cue procedure). Both groups learned the task, but they used different learning strategies. Telencephalon-ablated goldfish learned the task more quickly and made fewer errors to criterion than controls. Probe trials revealed that intact goldfish could use either a place or a cue strategy, whereas telencephalon-ablated goldfish learned only a cue strategy. The results offer additional evidence that place and cue learning in fish are subserved by different neural substrates and that the telencephalon of the teleost fish, or some unspecified structure within it, is important for spatial learning and memory in a manner similar to the hippocampus of mammals and birds.

Animals↗
PubMed1996

Place learning and hippocampal synaptic plasticity in streptozotocin-induced diabetic rats.

Moderate impairment of learning and memory has been recognized as a complication of diabetes. The present study examined behavioral and electrophysiological measures of cerebral function in streptozotocin (STZ)-induced diabetic rats. Behavioral testing consisted of a spatial learning task in a water maze. Electrophysiological testing consisted of in vitro assessment of hippocampal long-term potentiation (LTP), an activity-dependent form of synaptic plasticity, which is believed to be related to the cellular mechanisms of learning and memory. Two experiments were performed: the first with severely hyperglycemic rats and the second with moderately hyperglycemic rats. Rats were tested in the water maze 11 weeks after induction of diabetes. Next, LTP was measured in vitro in trained animals. Both spatial learning and LTP expression in the CA1 field of the hippocampus were impaired in severely hyperglycemic rats as compared with nondiabetic controls. In contrast, spatial learning and hippocampal LTP were unaffected in moderately hyperglycemic rats. The association of alterations in hippocampal LTP with specific learning impairments has previously been reported in conditions other than diabetes. Our findings suggest that changes in LTP-like forms of synaptic plasticity in the hippocampus, and possibly in other cerebral structures, are involved in learning deficits in STZ-induced diabetes. The beneficial effect of moderate glycemic control on both place learning and hippocampal LTP supports the significance of the relation between these two parameters and indicates that the development of the observed deficits may be related to the level of glycemic control.

Animals↗
PubMed1995

Spatial discrimination learning and choline acetyltransferase activity in streptozotocin-treated rats: effects of chronic treatment with acetyl-L-carnitine.

Treatment of rats with i.c.v. injected streptozotocin (STREP) may provide a relevant model of neurodegeneration that is induced by a decrease in the central metabolism of glucose. Acetyl-L-carnitine (ALCAR) enhances the utilization of alternative energy sources and by such a mechanism of action ALCAR could antagonize the effects of STREP treatment. In this study the effects of chronic treatment with ALCAR were evaluated on spatial discrimination learning in the Morris task and choline acetyltransferase (ChAT) activity of middle-aged STREP-treated rats. Chronic treatment with ALCAR attenuated both the STREP-induced impairment in spatial bias and the decrease in hippocampal ChAT activity. These findings indicate that ALCAR treatment has a neuroprotective effect, although further studies are needed to characterize the mechanism of action of ALCAR in this model.

Acetylcarnitine↗
PubMed2000

Behavioral effects of transient cerebral ischemia.

CA1 neurons in the hippocampus, a brain structure involved in learning and memory, are selectively vulnerable to ischemic effects. In this study, the authors examined if duration of ischemia is directly related to extent of CA1 damage and degree of spatial learning deficit. Adult female Wistar rats received either 5-min or 10-min ischemia or sham surgery. Following recovery, rats were tested in the Morris water maze. Histological analysis showed moderate cell loss in CA1 (31%) and CA3 (12%) and minimal cell loss in CA2 (4%) with 5-min ischemia. Increased cell loss was seen in CA1 (68%), CA2 (16%), and CA3 (23%) with 10-min ischemia. Behavioral testing revealed that animals with 10-min ischemia have greater spatial learning deficits and they remain impaired across the test days compared to the 5-min ischemic group. Furthermore, degree of CA1 cell loss accounted for approximately 45% of the variance in spatial learning deficits in the ischemic group. The authors conclude that cell loss is largely confined to CA1 region in rats who received 5 and 10 min of ischemia and that increased ischemic duration results in persistent learning deficits in female rats; also, the degree of behavioral impairment is related to extent of CA1 cell loss.

Animals↗
PubMed1995

Correlations between radial-maze learning and structural variations of septum and hippocampus in rodents.

Large, but non-pathological, individual differences in neuroanatomy of the brain exist in rodents, which have been shown to covary with behavioral traits. In the present review, we explore the relationship between variations in the extent of the intra- and infrapyramidal mossy fiber projection of the hippocampus and spatial and non-spatial learning capacities in mice and rats. Preliminary data concerning anatomical variation in the septo-hippocampal cholinergic system and its consequences for individual behavior are also presented. We conclude that the hippocampal intra- and infrapyramidal mossy fiber projection is intimately involved in the regulation of spatial, but not of non-spatial learning capabilities. Although lesion studies have shown that a well-functioning cholinergic system is a prerequisite for performance in spatial learning tasks, our preliminary data suggest that individual differences in the cholinergic system do not explain individual differences in learning.

Animals↗
PubMed1997

Multiple kainic acid seizures in the immature and adult brain: ictal manifestations and long-term effects on learning and memory.

PURPOSE: While there is increasing evidence that the adverse effects of prolonged seizures are less pronounced in the immature than in the mature brain, there have been few investigations of the long-term effects of recurrent seizures during development. This study examined the effects of multiple administrations of the convulsant kainic acid (KA) on seizure characteristics and spatial learning as a function of brain development. METHODS: To determine the long-term effects of serial KA seizures during ontogeny, saline or convulsant doses of KA were given intraperitoneally 4 times, at 2-day intervals. Immature rats were given KA on P20, P22, P24 and P26; adult rats got KA on P60, P62, P64 and P66. Ictal characteristics and EEGs were recorded. To examine the effects of multiple KA seizures on the retention of spatial learning, water maze testing was performed before (immature group: from P16-19, adult group: from P56-P59) and after (immature: from P60-P63, adult: from P100-P103) KA injections. Finally, histology was performed to compare KA-induced damage at each age. RESULTS: In immature animals, serial KA administration resulted in seizures with a progressively longer onset latency and decreased severity. In contrast, KA serially administered to adult rats caused severe seizures after each of the 4 injections. In immature rats, epileptiform EEG changes were most prominent after the first KA injection, whereas in adults, prolonged paroxysmal EEG patterns were seen after all 4 KA injections. Before KA, both rat pups and adults acquired place learning in the water maze. One month after the final KA injection, there was no deficit in spatial learning retention in the immature group, whereas the adult group had profound impairment compared to age-matched, saline-injected controls. Histology revealed no lesions in immature rats treated multiple times with KA but profound cell loss in hippocampal fields CA4, CA3 and CA1 in rats treated serially with KA as adults. CONCLUSIONS: Previous studies have shown that a single KA injection causes prolonged status epilepticus (which persists for several hours), leading to severe histologic and behavioral sequelae in adult rats but not in pups. Our study extends those findings, demonstrating that immature rats are spared the cognitive and pathological sequelae of multiple injections of convulsant doses of KA as well.

Animals↗
PubMed2001

Interaction between the cholinergic system and CRH in the modulation of spatial discrimination learning in mice.

Both cholinergic and CRH systems have been linked to cognitive processes such as learning and memory, and neuroanatomical as well as neurochemical evidence suggests important interactions between these two systems. Moreover, recent reports of pro-mnestic effects of CRH open the possibility that CRH could have beneficial effects in animals with cholinergic dysfunction. In a first experiment, spatial discrimination of C57BL/6 mice treated with various doses of scopolamine (0.5--2.0 mg/kg IP) was tested in a two-choice water maze task. Scopolamine, but not methylscopolamine, impaired accuracy and decreased responsivity. In contrast, similar doses of the nicotinic antagonist mecamylamine had no effect on choice accuracy but altered responsivity, as indicated by increased errors of omission and a reduction in swim speed during early experimental stages. ICV CRH (0.5--1.0 microg) also failed to significantly affect accuracy, but a strong tendency was observed to impair percentage correct responses. Measures of responsivity, such as errors of omission, choice latency and distance traveled, and of thigmotaxis were not significantly affected by CRH. However, initial swim speed was reduced by the peptide. Combined treatment with scopolamine (0.5 mg/kg IP) and CRH (0.5 microg ICV) had only mild, and primarily independent, effects, but overall suggested that concomitant blockade of muscarinic receptors and activation of the CRH system would rather act synergistically to disrupt spatial discrimination learning. Synergistic effects were also observed when animals receiving a combination of mecamylamine (2.0 mg/kg IP) and CRH (0.5 microg ICV) were tested, both in terms of responsivity and thigmotaxis, and there was limited evidence that part of these effects were potentiating. Thus, the cholinergic and CRH systems interact in the modulation of learning, but CRH, contrary to prediction, worsens the impairment caused by cholinergic blockade.

Acetylcholine↗
PubMed2000

[Spatial memory and hippocampus in aves].

The avian hippocampus, that locates in the posterior part of dorsomedial telencephalon, is considered to be a mammalian hippocampus homologue. The studies of connection, distribution of transmitters, and development of the avian hippocampus all support the homology. Food storing birds have large capacity of spatial memory and have a big hippocampus in comparison to non-storing species. The food-storing birds do not have good memory in general but have good memory specialized to the spatial tasks. The correlation between the volume of the hippocampus and behavior other than food storing but needs spatial memory is also suggested. The hippocampal damages cause deficits in spatial learning especially those using a maze but do not impair non-spatial learning tasks. These studies suggest that the avian hippocampus share a similar function with the mammalian hippocampus, especially that of rodents.

Animals↗
PubMed2005

Chronic administration of docosahexaenoic acid ameliorates the impairment of spatial cognition learning ability in amyloid beta-infused rats.

We investigated whether administration of docosahexaenoic acid (DHA), a major (n-3) fatty acid of the brain, ameliorates the impairment of learning ability in an animal model of Alzheimer's disease (AD), rats infused with amyloid-beta (Abeta) peptide (1-40) into the cerebral ventricle. Inbred 3rd generation male rats (20 wk old) fed a fish oil-deficient diet were randomly divided into 4 groups: a vehicle group, an Abeta peptide-infused group (Abeta group), a DHA group, and an Abeta + DHA group. A mini-osmotic pump filled with Abeta peptide or vehicle was implanted in the rats, and they were tested for learning ability-related reference and working memory in an 8-arm radial maze. The rats were then orally fed DHA dissolved in 5% gum Arabic solution at 300 mg/(kg . d) (DHA and Abeta + DHA groups) or vehicle alone (vehicle and Abeta groups) and tested again for learning ability. DHA administered for 12 wk significantly reduced the increase in the number of reference and working memory errors in the Abeta-infused rats, and increased both the cortico-hippocampal level of DHA and the molar ratio of DHA/arachidonic acid, suggesting an amelioration of the impaired spatial cognition learning ability. Furthermore, DHA suppressed the increases in the levels of lipid peroxide and reactive oxygen species in the cerebral cortex and the hippocampus of Abeta-infused rats, suggesting that DHA increases antioxidative defenses. DHA is thus a possible therapeutic agent for ameliorating learning deficiencies due to Alzheimer's disease.

Alzheimer Disease↗
PubMed2000

The effect of steroid sulfatase inhibition on learning and spatial memory.

Steroid sulfatase inhibitors can enhance the concentration of the neurosteroid DHEAS in rat brain. Previous studies have demonstrated that the steroid sulfatase inhibitor (p-O-sulfamoyl)-N-tetradecanoyl tyramine (DU-14) could reverse scopolamine induced amnesia in rats in a passive avoidance memory paradigm. The intent of this study was to determine whether chronic pretreatment with DU-14 could reverse scopolamine amnesia and/or enhance spacial memory in the place, probe and cued versions of the Morris water maze (MWM). Rats were divided into four groups and administered IP for 15 days either DU-14 (30.0 mg/Kg) or corn oil (1.0 ml/Kg) vehicle. On training days animals were administered either scopolamine (1.0 mg/Kg) or saline (1.0 ml/Kg). The groups administered DU-14 displayed a significant enhancement in learning and spacial memory in the place version of the MWM, when compared to respective vehicle-scopolamine and vehicle-saline groups. In the probe version, the DU-14-saline group remained in the target quadrant of the maze significantly longer than any of the other groups indicating enhanced retention. In the cued version of the MWM, treatment with DU-14 did not significantly change escape latency suggesting that the steroid sulfatase inhibitor did not alter motivation or locomotion. These results suggest that the chronic administration of steroid sulfatase inhibitors enhance learning and spatial memory in rats.

Amnesia↗