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At least 307 records · Page 17Linked to original sources

PubMed1999

Deprivation of endogenous brain-derived neurotrophic factor results in impairment of spatial learning and memory in adult rats.

Brain-derived neurotrophic factor (BDNF) is abundantly expressed in the hippocampus and cerebral cortex and is involved in synaptic plasticity and long-term potentiation (LTP). The present study was under taken to investigate whether endogenous BDNF was required for spatial learning and memory in a rat model. Antibodies to BDNF (anti-BDNF, n=7) or control immunoglobulin G (control, n=6) were delivered into the rat brain continuously for 7 days with an osmotic pump. The rats were then subjected to a battery of behavioral tests. The results show that the average escape latencies in the BDNF antibody treated group were dramatically longer than those of the control (F=13.3, p<0.001). The rats treated with control IgG swam for a significantly longer distance in the P quadrant (where the escape plane had been placed) compared with the other three quadrants (p<0.05). In contrast, anti-BDNF-treated rats swam an equivalent distance in all four quadrants. The average percentage of swimming distance in the P quadrant by anti-BDNF-treated rats was much less than that by control IgG treated rats (p<0.001). These results suggest that endogenous BDNF is required for spatial learning and memory in adult rats.

Animals↗

PubMed1997

Roles of movement and temporal factors in spatial learning.

Previous experiments suggested that rats can learn to discriminate between adjacent arms of an eight-arm radial maze if they have an intact hippocampal system and are allowed to move around on the maze. These requirements are consistent with the hypothesis that this discrimination involves hippocampus-based spatial learning. We examined the importance of self-generated movement in this form of learning by moving rats manually ("passive movement") between two adjacent maze arms within a single training trial. Rats moved passively between arms (only one of which contained food) within trials learned to discriminate between the arms, as measured by a conditioned preference for the food arm when both arms were empty. This form of learning was impaired by lesions of fimbria-fornix, but was unaffected by lesions of the lateral nucleus of the amygdala. Normal rats that were picked up and replaced on the same arm within trials and experienced their food and no food arms on different daily trials failed to learn the same discrimination. These findings suggest that self-generated movement is not required for spatial learning that may be mediated by a hippocampal system; rather, movement may simply serve to provide information from different locations about the cues in an environment.

Amygdala↗

PubMed1998

Continuous blockade of brain glucocorticoid receptors facilitates spatial learning and memory in rats.

Previously, a corticosterone surge associated with a learning task was shown to facilitate cognitive processes through brain glucocorticoid receptors (GR) while chronic overexposure to this stress hormone impaired cognition. In the present study we tested the hypothesis that opposing effects on learning and memory might also occur after either phasic or continuous blockade of brain GR by intracerebroventricular (i.c.v.) administration of the GR antagonist RU38486 (aGR). We used a Morris water maze procedure to assess spatial learning and memory abilities in male Wistar rats. The effect of phasic brain GR blockade was studied following daily pretraining administration of 10 and 100 ng/microL aGR i.c.v. on 3 consecutive days. This repetitive aGR treatment impaired spatial learning and memory dose-dependently in comparison with vehicle controls. For continuous brain GR blockade, animals received an i.c.v., infusion of aGR (10 and 100 ng/0.5 microL per h or vehicle) over 10 days. Infusion of 100 ng aGR per hour resulted in a long-lasting facilitation of spatial performance. The 10 ng aGR infusion also caused initially a facilitating effect, which was, however, transient and performance became impaired during retest. Possible anxiolytic properties of the drugs were excluded in view of the animals' behaviour in the elevated plus maze. Both doses of aGR infusion reduced the number of mineralocorticoid receptors in the hippocampus, but only the high dose of aGR resulted in a significant reduction of available GR sites. In conclusion, continuous administration of GR antagonist improves cognitive function, while phasic blockade of brain GR function causes a cognitive deficit.

Adrenocorticotropic Hormone↗

PubMed2004

Effects of histamine H3 receptor antagonists in two models of spatial learning.

Despite the well-described attention and short-term memory enhancing effects of H3 receptor antagonists, and evidence to suggest a close relationship between central histaminergic and cholinergic systems, there is a paucity of evidence for a role for H3 receptor blockade in spatial learning. To address this, we investigated two H3 receptor antagonists in a visual discrimination water maze in rats, and in a Barnes circular maze in mice. Thioperamide and ciproxifan significantly attenuated a scopolamine-induced deficit in the water maze task, while only ciproxifan showed a modest attenuation in the Barnes maze. Taken together, these data suggest a role for H3 receptors in spatial learning that appears to be task-dependent.

Animals↗

PubMed2002

Impaired spatial learning and hyperactivity in developing rats exposed to intermittent hypoxia.

Obstructive sleep apnea (OSA) is a frequent medical condition and is associated with cognitive impairments in adults and with hyperactivity and decreased school performance in children. In an adult rodent model, intermittent hypoxia (IH), such as occurs in OSA, is associated with neurodegenerative changes in the hippocampus and cortex and with spatial learning deficits. Because a unique developmental window of neural vulnerability to IH is present, we hypothesized that exposure to IH throughout the vulnerable ages would result in increased behavioral impairments in the juvenile rat. Rat pups were therefore exposed to either room air or IH beginning at postnatal (PN) d 10 until PN d 30. Learning and memory were assessed via a standard place-training version of the Morris water maze beginning at PN d 25. Locomotor activity was assessed on PN d 29 and 30. Pups exposed to IH displayed significant spatial learning impairments, and exposed male rats but not female rats displayed increased locomotor activity in the open field. Collectively, these findings indicate that exposure to IH at an age that corresponds to the peak incidence of OSA in children induces substantial learning impairment and gender-dependent behavioral hyperactivity in the juvenile rat. We postulate that this novel experimental model may allow for future exploration of mechanisms underlying the neurobehavioral deficits of children with OSA.

Adolescent↗

PubMed1998

Fimbria-fornix vs selective hippocampal lesions in rats: effects on locomotor activity and spatial learning and memory.

The behavioral effects of interrupting the axons that pass in the fimbria and dorsal fornix were compared with the effects of selective removal of the cells that comprise the hippocampus with ibotenic acid. Starting 4.5 months after surgery, lesioned and control rats were (i) trained in both the Morris water maze and the eight-arm radial maze using protocols that placed an emphasis on either working memory (WM) or reference memory (RM) and (ii) tested for locomotor activity in the home cage. In comparison to sham-operated rats, the rats from both lesion groups were impaired in most learning/memory tasks, but there were some interesting differences between the two lesioned groups. When compared to rats with fimbria-fornix lesions (FIFX rats), hippocampal rats (HIPP rats) were slower in learning to swim to a visible platform and showed a greater impairment than FIFX rats in the radial-maze task when the testing procedure required the utilization of RM and WM in a more demanding WM task. In the test of locomotor activity, FIFX and control rats did not differ, but HIPP rats were more active than the rats in both other groups. The pattern of results obtained after a 4.5-month recovery period support the following general conclusions. (1) While there are some similarities in the effects on behavior of interrupting the axons in the fimbria-fornix compared to removing the hippocampus, there are some important differences. (2) From the findings that are available, a possible explanation to account for the difference between FIFX and HIPP rats is that the 4.5-month survival time permitted some recovery in the group of rats with FIFX lesions. (3) While it is well known that the Morris water maze and the radial-arm maze tasks provide useful measures of spatial learning and memory processes, our results suggest that the information provided by the two spatial learning tasks may differ in important respects.

Analysis of Variance↗

PubMed1996

Spatial learning deficit in mice expressing human 751-amino acid beta-amyloid precursor protein.

Cognitive and other behavioural characteristics of 3-month-old heterozygous male transgenic mice expressing the 751-amino acid isoform of human amyloid precursor protein (hAPP751) under the control of a neurone-specific enolase promoter, were compared with those of age-matched non-transgenic control males. No difference was found between hAPP751 transgenics and non-transgenic controls in passive avoidance learning, or in motor coordination. Significantly decreased measures were found in the open field test and in cage activity indicative of general hypoactivity in hAPP751 transgenics. In water maze training, hAPP751 males required significantly longer to locate the hidden platform. This was not due to decreased swimming velocity in hAPP751 mice, but rather to increased path lengths. This suggests a purely spatial learning deficit in hAPP751 males even though their performance during a final spatial test, the probe trail that followed water maze training, was indistinguishable from that of controls. Decreased activity and impaired spatial learning were also reported in an independent study of hAPP751-expressing transgenics showing beta-amyloid immunoreactive deposits and altered tau protein. Since such histopathological alterations were not found in the transgenic model analysed in this study, our results indicate that beta-amyloid deposition is not required for the development of behavioural and/or cognitive deficits in hAPP751 transgenic mice.

Amyloid beta-Protein Precursor↗

PubMedDate not supplied

Impairment of spatial learning and hippocampal synaptic potentiation in c-kit mutant rats.

The c-kit receptor tyrosine kinase encoded by the white-spotting (W) gene is highly expressed in rat hippocampal CA1-CA4 regions. We found an impaired spatial learning and memory in homozygous c-kit (Ws/Ws) mutant rats that have a 12-base deletion in the tyrosine kinase domain of the c-kit gene and a very low kinase activity. Electrophysiological studies in hippocampal slices revealed that the long-term potentiation (LTP) induced by the tetanic stimulation (100 Hz, 1 sec) in the mossy fiber (MF)-CA3 pathway, but not in the Schaffer collaterals/commissural-CA1 pathway, was significantly reduced in c-kit mutants compared with wild-type (+/+) rats. The paired-pulse facilitation (PPF) was measured before the tetanus and after the establishment of the LTP in each slice. The initial PPF in the MF-CA3 pathway positively correlated with the amplitude of the LTP in the wild-type rats but not in the c-kit mutant rats. Furthermore, they failed to show the normal characteristics observed in the MF-CA3 pathway of +/+ rats; that is, the negative correlation between the initial PPF and the changes in PPF measured after the LTP. These findings suggest an involvement of SCF/c-kit signaling in hippocampal synaptic potentiation and spatial learning and memory.

Animals↗

PubMed1998

Deficits in spatial learning after exposure of mice to a 50 Hz magnetic field.

A series of four experiments was performed to determine the effect of exposure to a 50 Hz magnetic field on memory-related behaviour of adult, male C57BL/6J mice. Experimental subjects were exposed to a vertical, sinusoidal magnetic field at 0.75 mT (rms), for 45 min immediately before daily testing sessions on a spatial learning task in an eight-arm radial maze. Control subjects were only exposed to a background time-varying field of less than 50 nT and the ambient static field of about 40 microT. In each experiment, exposure significantly reduced the rate of acquisition of the task but did not affect overall accuracy. This finding is consistent with the results of another study that found that prior exposure to 60 Hz magnetic fields affected spatial learning in rats.

Animals↗

PubMed2004

Effect of I.C.V. injection of AT4 receptor ligands, NLE1-angiotensin IV and LVV-hemorphin 7, on spatial learning in rats.

Central administration of angiotensin IV (Ang IV) or its analogues enhance performance of rats in passive avoidance and spatial memory paradigms. The purpose of this study was to examine the effect of a single bolus injection of two distinct AT4 ligands, Nle1-Ang IV or LVV-haemorphin-7, on spatial learning in the Barnes circular maze. Mean number of days for rats treated with either Nle1-Ang IV or LVV-haemorphin-7 to achieve learner criterion is significantly reduced compared with controls (P < 0.001 and P < 0.05 respectively). This is due to enhanced ability of the peptide-treated rats to adopt a spatial strategy for finding the escape hatch. In all three measures of learning performance, (1) the number of errors made, (2) the distance travelled and (3) the latency in finding the escape hatch, rats treated with either 100 pmol or 1 nmol of Nle1-Ang IV or 100 pmol LVV-haemorphin-7 performed significantly better than the control groups. As early as the first day of testing, the rats treated with the lower dose of Nle1-Ang IV or LVV-haemorphin-7 made fewer errors (P < 0.01 and P < 0.05 respectively) and travelled shorter distances (P < 0.05 for both groups) than the control animals. The enhanced spatial learning induced by Nle1-Ang IV (100 pmol) was attenuated by the co-administration of the AT4 receptor antagonist, divalinal-Ang IV (10 nmol). Thus, administration of AT4 ligands results in an immediate potentiation of learning, which may be associated with facilitation of synaptic transmission and/or enhancement of acetylcholine release.

Angiotensin II↗

PubMed1992

Impaired long-term potentiation, spatial learning, and hippocampal development in fyn mutant mice.

Mice with mutations in four nonreceptor tyrosine kinase genes, fyn, src, yes, and abl, were used to study the role of these kinases in long-term potentiation (LTP) and in the relation of LTP to spatial learning and memory. All four kinases were expressed in the hippocampus. Mutations in src, yes, and abl did not interfere with either the induction or the maintenance of LTP. However, in fyn mutants, LTP was blunted even though synaptic transmission and two short-term forms of synaptic plasticity, paired-pulse facilitation and post-tetanic potentiation, were normal. In parallel with the blunting of LTP, fyn mutants showed impaired spatial learning, consistent with a functional link between LTP and learning. Although fyn is expressed at mature synapses, its lack of expression during development resulted in an increased number of granule cells in the dentate gyrus and of pyramidal cells in the CA3 region. Thus, a common tyrosine kinase pathway may regulate the growth of neurons in the developing hippocampus and the strength of synaptic plasticity in the mature hippocampus.

2-Amino-5-phosphonovalerate↗

PubMed1987

Effects of chronic diisopropylfluorophosphate treatment on spatial learning in mice.

The Morris water task was used to measure the effects of chronic diisopropylfluorophosphate (DFP) treatment on C57BL/6Ibg mice. Control mice showed good task acquisition and searched accurately for the platform after it was removed from the pool, suggesting that they had formed a spatial map of the platform's location relative to distal cues. In contrast, mice chronically treated with DFP prior to training showed a marked deficit in spatial learning. Chronic DFP treatment did not affect ability to locate a visible platform and did not impair task retention in mice trained to find the hidden platform prior to DFP treatment. The chronic DFP treatment decreased muscarinic binding in cortex, hippocampus, and striatum. These results indicate that C57BL mice are capable of spatial learning in the water task. The ability of chronic DFP treatment to impair place but not cue learning suggests that the cholinergic dysfunction produced by DFP is similar to those produced by lesions of central cholinergic systems and acute treatments with muscarinic antagonists.

Animals↗

PubMed2005

Emotional and spatial learning in goldfish is dependent on different telencephalic pallial systems.

In mammals, the amygdala and the hippocampus are involved in different aspects of learning. Whereas the amygdala complex is involved in emotional learning, the hippocampus plays a critical role in spatial and contextual learning. In fish, it has been suggested that the medial and lateral region of the telencephalic pallia might be the homologous neural structure to the mammalian amygdala and hippocampus, respectively. Although there is evidence of the implication of medial and lateral pallium in several learning processes, it remains unclear whether both pallial areas are involved distinctively in different learning processes. To address this issue, we examined the effect of selective ablation of the medial and lateral pallium on both two-way avoidance and reversal spatial learning in goldfish. The results showed that medial pallium lesions selectively impaired the two-way avoidance task. In contrast, lateral pallium ablations impaired the spatial task without affecting the avoidance performance. These results indicate that the medial and lateral pallia in fish are functionally different and necessary for emotional and spatial learning, respectively. Present data could support the hypothesis that a sketch of these regions of the limbic system, and their associated functions, were present in the common ancestor of fish and terrestrial vertebrates 400 million years ago.

Animals↗

PubMed2003

Exercise increases hippocampal neurogenesis to high levels but does not improve spatial learning in mice bred for increased voluntary wheel running.

The hippocampus is important for the acquisition of new memories. It is also one of the few regions in the adult mammalian brain that can generate new nerve cells. The authors tested the hypothesis that voluntary exercise increases neurogenesis and enhances spatial learning in mice selectively bred for high levels of wheel running (S mice). Female S mice and outbred control (C) mice were housed with and without running wheels for 40 days. 5-Bromodeoxyuridine was used to label dividing cells. The Morris water maze was used to measure spatial learning. C runners showed a strong positive correlation between running distance and new cell number, as well as improved learning. In S runners, neurogenesis increased to high levels that reached a plateau, but no improvement in learning occurred. This is the first evidence that neurogenesis can occur without learning enhancement. The authors propose an alternative function of neurogenesis in the control of motor behavior.

Animals↗

PubMed2006

The effect of intrahippocampal insulin microinjection on spatial learning and memory.

Insulin is best known for its action on peripheral target tissues such as the adipocyte, muscle and liver to regulate glucose homeostasis. Insulin and its receptor are found in specific area of CNS with a variety of region-specific functions different from its direct glucose regulation in the periphery. The hippocampus and cerebral cortex distributed insulin/insulin receptor has been shown to be involved in brain cognitive functions. Previous studies about the effect of insulin on memory are controversial. In the present study, the effect of insulin microinjection into CA1 region of rat hippocampus on water maze performance has been investigated. Insulin had a discrepant effect dose dependently. The spatial learning and memory were impaired with lower dose of insulin, had not changed with intermediate doses, while they improved with higher doses. These results suggest that insulin may have a dose-dependent effect on spatial learning and memory.

Animals↗

PubMed2002

Spatial learning, exploration, anxiety, and motor coordination in female APP23 transgenic mice with the Swedish mutation.

Transgenic mice overexpressing the betaAPP gene with the Swedish mutation under the control of the murine thy-1 promoter show Alzheimer-like characteristics including the accumulation of Abeta protein in the cerebral cortex. Female 16-month-old APP23 transgenic mice were compared to age-matched non-transgenic mice in behavioral tests measuring spatial learning, exploration of environmental stimuli, anxiety, and motor coordination. APP23 transgenic mice had fewer fast ambulatory movements, either fast or slow stereotypy movements, and slow rears in a photocell activity chamber. The acquisition of spatial learning in the Morris water maze was impaired in APP23 transgenic mice, but not during the probe test or while swimming towards a visible platform. Neither were there intergroup differences in tests of anxiety or motor coordination. These results indicate that a learning deficit and hypoactivity, concordant with the early stages of Alzheimer's disease, characterize this mouse model with Abeta accumulation.

Alzheimer Disease↗

PubMed2005

Cyclooxygenase inhibition attenuates endotoxin-induced spatial learning deficits, but not an endotoxin-induced blockade of long-term potentiation.

Peripheral administration of lipopolysaccharide (LPS), a potent bacterial endotoxin, can cause a variety of central effects, including production of cytokines and cyclooxygenases in the brain, as well as peripheral increases in corticosterone. These, in turn, may contribute to neuroimmune-induced neurocognitive deficits. We show here LPS causes deficits in hippocampal-dependent spatial learning in the water maze but that treatment with ibuprofen, a broad-spectrum cyclooxygenase inhibitor, reverses the deficits induced in spatial learning by LPS. We also show that LPS causes an impairment in the induction of long-term potentiation in the dentate gyrus in vivo, a major contemporary model of learning and memory. No differences were found in corticosterone levels in trunk blood but we find a decrease in brain-derived neurotrophic factor (BDNF) expression in LPS group compared to saline controls. Paradoxically compared to the behavioral findings treatment with ibuprofen does not attenuate the LPS-induced impairment in LTP or BDNF concentration in tetanized tissue.

Brain-Derived Neurotrophic Factor↗

PubMed2005

A lateralized avian hippocampus: preferential role of the left hippocampal formation in homing pigeon sun compass-based spatial learning.

The hippocampal formation (HF) plays a crucial role in amniote spatial cognition. There are also indications of functional lateralization in the contribution of the left and right HF in processes that enable birds to navigate space. The experiments described in this study were designed to examine left and right HF differences in a task of sun compass-based spatial learning in homing pigeons (Columba livia). Control, left (HFL) and right (HFR) HF lesioned pigeons were trained in an outdoor arena to locate a food reward using their sun compass in the presence or absence of alternative feature cues. Subsequent to training, the pigeons were subjected to test sessions to determine if they learned to represent the goal location with their sun compass and the relative importance of the sun compass vs. feature cues. Under all test conditions, the control pigeons demonstrated preferential use of the sun compass in locating the goal. By contrast, the HFL pigeons demonstrated no ability to locate the goal by the sun compass but an ability to use the feature cues. The behaviour of the HFR pigeons demonstrated that an intact left HF is sufficient to support sun compass-based learning, but in conflict situations and in contrast to controls, they often relied on feature cues. In conclusion, only the left HF is capable of supporting sun compass-based learning. However, preferential use of the sun compass for learning requires an intact right HF. The data support the hypothesis that the left and right HF make different but complementary contributions toward avian spatial cognition.

Animals↗