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PubMed1990

Concurrent muscarinic and beta-adrenergic blockade in rats impairs place-learning in a water maze and retention of inhibitory avoidance.

These experiments examined the effects of separate and concurrent muscarinic cholinergic and beta-adrenergic blockade on inhibitory (passive) avoidance performance and spatial learning in the Morris water maze. Pretraining systemic administration of either scopolamine (0.3 or 1.0 mg/kg) or propranolol (3.0 or 10.0 mg/kg) had no significant effect on one-day retention of step-through inhibitory avoidance training. Similarly, pretraining administration of either 0.3 mg/kg scopolamine or 10 mg/kg propranolol did not affect spatial learning in the Morris water maze. However, combined administration of scopolamine and 10.0 mg/kg of propranolol impaired performance on these tasks. These findings further support a role for interactions between norepinephrine and acetylcholine in the modulation of learning and memory and implicate the participation of beta-adrenergic mechanisms in this interaction. Because cholinergic and noradrenergic deterioration is found in aging and Alzheimer's disease, these results also have implications regarding the role of age-related noradrenergic and cholinergic dysfunction in cognitive decline.

Animals↗
PubMed2005

Glucose injections into the dorsal hippocampus or dorsolateral striatum of rats prior to T-maze training: modulation of learning rates and strategy selection.

The present experiments examined the effects of injecting glucose into the dorsal hippocampus or dorsolateral striatum on learning rates and on strategy selection in rats trained on a T-maze that can be solved by using either a hippocampus-sensitive place or striatum-sensitive response strategy. Percentage strategy selection on a probe trial (P(crit)) administered after rats achieved criterion (nine of 10 correct choices) varied by group. All groups predominately exhibited a response strategy on a probe trial administered after overtraining, i.e., after 90 trials. In experiment 1, rats that received intrahippocampal glucose injections showed enhanced acquisition of the T-maze and showed increased use of response solutions at P(crit) compared with that of unimplanted and artificial cerebral spinal fluid (aCSF)-treated groups. These findings suggest that glucose enhanced hippocampal functions to accelerate the rate of learning and the early adoption of a response strategy. In experiment 2, rats that received intrastriatal glucose injections exhibited place solutions early in training and reached criterion more slowly than did aCSF controls, with learning rates comparable to those of unoperated and operated-uninjected controls. Relative to unoperated, operated-uninjected and glucose-injected rats, rats that received intrastriatal aCSF injections showed enhanced acquisition of the T-maze and increased use of response solutions at P(crit). The unexpected enhanced acquisition seen after striatal aCSF injections suggests at least two possible interpretations: (1) aCSF impaired striatal function, thereby releasing competition with the hippocampus and ceding control over learning to the hippocampus during early training trials; and (2) aCSF enhanced striatal functioning to facilitate striatal-sensitive learning. With either interpretation, the results indicate that intrastriatal glucose injections compensated for the aCSF-induced effect. Finally, enhanced acquisition regardless of treatment was accompanied by rapid adoption of a response solution for the T-maze.

Animals↗
PubMed1995

Learning set spatial navigation performance in three mouse strains.

Swiss Webster (SW), Dilute Brown Agouti (DBA), and Deer Mice (DM) were tested for acquisition and retention of a learning set place task in the Morris water maze. The learning set consisted of daily placing the hidden platform sequentially at 1 of 4 separate locations in the pool. All animals swam for 63 days in this version of the water task. SW animals were unable to find the platform reliably. The time taken by DBA and DM animals in escaping the pool declined rapidly, reaching asymptote within 21 days. The DM animals reached the platform significantly faster than either SW or DBA mice. Analyses of swim path selection used by the 3 strains indicated clearly that DM mice were the most systematic in the selecting and sequencing from a variety of potential strategies the appropriate methods necessary for the most efficient solution of the problem. The present results suggest that in light of the differences between strains observed in swimming behaviors, investigation of strain differences in the neuroanatomic structures believed to be related to the solving of spatial problems might be useful.

Animals↗
PubMed2002

Testing the spatial- versus object-learning distinction: water-maze performance of male rats exposed to ethanol during the brain growth spurt.

This study investigated the effects of exposure to ethanol during the brain growth spurt on a visual-discrimination (VD) and a place-learning task (PL) using intra-maze cues in the water maze. Artificially reared male Long-Evans rats were exposed to ethanol (ET) in a binge pattern from postnatal days 6-9 (6.5 g kg(-1) x day(-1); BAC approximately 330 mg/dl) or an isocaloric maltose-dextrin solution (gastrostomy control). A third suckled control group was reared by lactating dams. In experiment 1, rats were trained to discriminate horizontal- (H) versus vertical-striped (V) cues, with the positive cue providing escape from water. Groups did not differ with V+, but ET rats made more errors with H+. In experiment 2, the ET group was impaired in learning the spatial location of a submerged platform relative to intra-maze cues. In both tasks, acquisition deficits among ET rats were characterized by impairment emerging at trial 2, with intact reference memory on trial 1, and the ET group reached a comparable level of performance to controls by the end of training. In summary, because impairment was related to task characteristics, a clear distinction between impaired spatial- versus cue-based learning was not supported. However, these findings do support an effect of exposure to ethanol during the brain growth spurt on recent event, but not reference, memory.

Animals↗
PubMed1999

Hippocampal place cells can develop distinct representations of two visually identical environments.

The pattern separation ability of hippocampal place cells was tested in an environment in which two visually identical rectangular compartments (Box A and Box B) were connected by a hidden door. Small ensembles of neurons were recorded with tetrodes while the rat searched for randomly distributed loci for reinforcing brain stimulation. The first recording session in Box A was conducted after the rat had explored the environment for the first time for 30 min. Immediately thereafter, a hidden door between Box A and Box B was opened to let the rat into the unexplored compartment, and a 5-min recording session was run with the door concealed. A rearrangement of place fields in Box B was observed in 18/20 neurons and in 5/6 ensembles. Most place fields did not change between two successive sessions in Box B. When the rat returned to Box A, the ensembles of neurons were as likely to adopt the original Box A firing field pattern as the more recent Box B pattern. In order to control for the influence of extra-arena cues, the rat was gradually lifted in a closed bucket from Box A into Box B while the whole arena was rotated by 90 degrees. All but one neuron and all the ensembles followed the intra-arena cues. Both rotated Box B and Box A firing field patterns were represented but Box B pattern was stronger among the neuronal ensembles. These findings indicate that hippocampal place cells not only can develop distinct representations of two visually identical environments but also can selectively reactivate either one of these representations depending on the rat's recent experience.

Animals↗
PubMedDate not supplied

The effects of peripheral endocrine hormone deficiencies on the processes of behavior, learning, and memory.

The effects of thyroid and adrenal cortex hormone and sex hormone deficiencies on the ability to learn, store memory traces, and behave were compared in male rats. These studies showed that removal of peripheral endocrine glands led to disruption of the learning process and the ability to reproduce learned information and also produced alterations in behavior. Analysis of the results showed that corticosteroid hormones are directly involved in the processes of learning and behavior. Sex and thyroid hormones appear to have modulatory effects on higher nervous activity.

Adrenal Cortex Hormones↗
PubMed1996

Influence of iron deficiency and lead treatment on behavior and cerebellar and hippocampal polyamine levels in neonatal rats.

Effect of lead exposure and iron-deficiency on polyamine levels in neuronal and glial cells of cerebellum and hippocampus was investigated in weaned rats. Lactating dams with one day old litters were given 0.2% (w/v) lead acetate in drinking water from postnatal day one to twenty one and maintained on an iron-deficient diet. There was an overall reduction of putrescine, spermidine and spermine in neuronal and glial cells of cerebellum and hippocampus consequent to lead exposure and iron-deficiency alone. Lead exposure and iron-deficiency together did not potentiate the polyamine levels in neuronal and glial cells of cerebellum and hippocampus uniformly. However, the enhanced lowering of putrescine in the hippocampal glia, spermidine in cerebellar neuronal and spermine in both neuronal and glial cells of cerebellum during the critical stage of brain development may result in stunted neuronal growth and sprouting in lead exposed and iron-deficient animals. The behavioral alterations as observed in the present study may be due to impaired neuronal development resulting from a depressed polyamine pathway and which could be attributed to cognitive deficits in growing children.

Analysis of Variance↗
PubMed1999

Ganglioside GM1 attenuates scopolamine-induced amnesia in rats and mice.

Some experimental evidence suggests that the beneficial effects of monosialoganglioside GM1 on learning and memory could be related to an improving effect in central cholinergic function. The present study investigates the effects of GM1 on the memory impairment induced by scopolamine in rats or mice tested in passive (PA) and discriminative avoidance (DA) tasks, respectively. Wistar EPM-1 male rats and Swiss EPM-M1 male mice were treated daily IP with 50 mg/kg GM1 or saline for 7 or 14 days, respectively. Twenty-four hours after the last injection, GM1-treated animals received 1 mg/kg scopolamine (GM1-SCO) and saline-treated animals received 1 mg/kg scopolamine (SAL-SCO) or saline (SAL-SAL) IP. Twenty minutes later, the animals were submitted to PA or DA conditioning, and tests were performed 24 h later. The latency in entering the dark chamber of the PA apparatus (LD) presented by SAL-SCO rats was significantly decreased when compared to that presented by SAL-SAL animals. GM1-SCO animals showed an increased LD when compared to SAL-SCO animals and were not significantly different from SAL-SAL rats. GM1-SCO and SAL-SAL (but not SAL-SCO) mice spent significantly less time in the aversive enclosed arm of the discriminative avoidance apparatus when compared to the time spent in the non-aversive enclosed arm. The results are consistent with the interpretation that GM1 attenuates scopolamine-induced amnesia. Although not eliminating the participation of other transmitter systems, the present study indicates a possible role of central cholinergic transmission in the action of this compound on learning and memory.

Amnesia↗
PubMed1996

Effects of beta-CCE on retention of aversively- and appetitively-motivated tasks in rats.

Beta-carboline-3-carboxylic acid ethyl ester (beta-CCE; 1.0 or 5.0 mg/kg, i.p.) or vehicle control was administered to male Sprague-Dawley rats immediately after training in an aversively- or appetitively-motivated task. Aversively-motivated training consisted of a one-trial step-though inhibitory (passive) avoidance task with a 0.6 mA, 1.0 s foot shock. Retention was tested 21 days after training. The 5.0 mg/kg dose of beta-CCE significantly enhanced retention performance in the inhibitory avoidance task compared to the vehicle control. For appetitive training, the animals learned a T-maze for water reward. Retention was tested 48 h later, and neither dose of beta-CCE was found to affect retention performance. These results suggest that beta-CCE, when administered immediately after training, may alter retention performance of an aversively-motivated task but not an appetitive task.

Animals↗
PubMed1995

Reversal of age-dependent cognitive impairments and cholinergic neuron atrophy by NGF-secreting neural progenitors grafted to the basal forebrain.

A highly NGF-secreting cell line was generated by retroviral transduction of a conditionally immortalized CNS-derived neural progenitor cell line. After transplantation to the nucleus basalis magnocellularis (NBM), the cells continue to express the NGF transgene for at least 10 weeks, producing sufficient NGF to reverse cholinergic neuron atrophy in aged rats and induce cellular hypertrophy in young rats. In cognitively impaired aged rats, transplants of the NGF-secreting cells placed either in the NBM and septum or in only the NBM induced a near-complete reversal of the spatial learning impairment. This was accompanied by a normalization of the size of the cholinergic neurons in the grafted areas. The results demonstrate that locally increased supply of NGF to the basal forebrain cholinergic nuclei has a significant impact on cognitive function and support the usefulness of neural progenitor cells for a long-term localized delivery of neurotrophins to the CNS.

Age Factors↗
PubMed2005

Verbal mediation and memory for novel figural designs: a dual interference study.

To the extent that all types of visual stimuli can be verbalized to some degree, verbal mediation is intrinsic in so-called "visual" memory processing. This impurity complicates the interpretation of visual memory performance, particularly in certain neurologically impaired populations (e.g., aphasia). The purpose of this study was to investigate the relative contributions of verbal mediation to recognition memory for visual stimuli that vary with respect to their amenability to being verbalized. In Experiment 1, subjects attempted to verbally describe novel figural designs during presentation and then identify them in a subsequent recognition memory test. Verbalizing these designs facilitated memory. Stimuli that were found to be easiest or most difficult to verbalize at the group level were retained for the second study. In Experiment 2, subjects evidenced superior recognition memory for the relatively easy to verbalize items. This advantage was attenuated in subjects who performed a concurrent verbal interference task during encoding, but not in those who performed an analogous visual interference task. These findings provide evidence that impoverished verbal mediation disproportionately impedes memory for visual material that is relatively easy to verbalize. Implications for the clinical assessment of visual memory are discussed.

Association Learning↗
PubMed2004

Posterior neocortical (visual cortex) lesions in the rat impair matching-to-place navigation in a swimming pool: a reevaluation of cortical contributions to spatial behavior using a new assessment of spatial versus nonspatial behavior.

In the face of contradictory findings on the role of visual cortex contributions to spatial behavior, the present study evaluated the ability of rats with primary visual cortex (area 17) lesions to learn spatial problems in a swimming pool. Because the solution to any spatial learning problem consists of acquiring at least two primary elements of a task, task procedures and spatial learning, the study, in addition to assessing spatial ability on a place task, used two training/testing methods to identify the nature of the spatial impairment associated with visual cortex lesions. Non-spatial training consisted of learning to find a platform in the dark and spatial training consisted of a series of matching-to-place problems. The results confirmed that although rats with visual cortex lesions were impaired on place learning, the deficit was partially ameliorated by non-spatial training given following the lesion, and completely ameliorated by non-spatial training given before the lesion. Nevertheless, all visual cortex groups failed to show a quadrant preference on a probe trial and displayed a profound impairment in matching-to-place learning. This definitive demonstration that appropriate testing methods can reveal a failure in spatial behavior following visual cortex lesions is consistent with the idea that primary visual cortex is required in spatial navigation.

Animals↗
PubMed2005

The effect of intrahippocampal injection of testosterone enanthate (an androgen receptor agonist) and anisomycin (protein synthesis inhibitor) on spatial learning and memory in adult, male rats.

In most mammals, the hippocampus has a well-documented role in spatial memory acquisition. High concentration of androgen receptors in fundamental centers of learning and memory in brain such as hippocampus shows that there may be some relationships between androgen receptors and cognitive aspects of brain. Previous studies, which have shown sex-dependent differences in hippocampal morphology and physiology, suggest a modulatory role for sex steroids in hippocampal function. Androgens have been shown to modulate some hippocampal-mediated behaviors including learning and memory. To study the mechanism of action of androgens in processes underlying learning and memory, anisomycin, a protein synthesis inhibitor was used to prevent the genomic effects of testosterone. Therefore, the effects of anisomycin and testosterone together were assessed on rat's performance in MWM. Rats received anisomycin (2.5 microg/0.5 microl), testosterone (80 microg/0.5 microl) or both anisomycin (2.5 microg/0.5 microl) and testosterone (80 microg/0.5 microl) through the connulas in the CA1 region. Anisomycin was injected 20 min and testosterone was injected 35 min before training each day. The results showed that anisomycin (2.5 microg/0.5 microl) and testosterone (80 microg/0.5 microl) increased latencies to find the invisible platform. But the group that received testosterone and anisomycin together was decrease in latency and traveled distance to find the invisible platform.

Androgen Receptor Antagonists↗
PubMed2006

Spatial learning in Long-Evans Hooded rats and C57BL/6J mice: different strategies for different performance.

Spatial learning abilities of rodents have been extensively used to explore the management of a wide range of cognitive and emotional processes such as learning, memory, attention and anxiety. Knowledge about the organization and processing of spatial learning has mainly been obtained in rats. Due to increasing generation of genetically modified mice, cognitive abilities of mice are now extensively tested. The present paper aimed at comparing spatial representation, learning and strategies in C57BL/6J mice and Long-Evans Hooded rats when subjected to the same spatial learning paradigm, i.e. learning a food location in a crossmaze. We also analyzed the influence of environmental richness on learning modalities in both species. Our results showed that rats and mice could exhibit similar spatial learning abilities in some circumstances. However, Long-Evans rats and C57BL/6J mice may set up different strategies depending on the availability of visual information within the environment. Rats' learning strategies mainly relied on distant visual cues and seemed more efficient than those used by mice as they needed less time than mice to solve the task. We emphasize that the strategies of mice are less robust and flexible than the ones set up by rats. Finally, the richness of the environment was shown to affect speed and quality of spatial learning in both species.

Analysis of Variance↗
PubMed2004

Transfer between views of conspecific faces at different ages or in different orientations by sheep.

Sheep are able to discriminate photographs of conspecific faces. The present study investigates adult ewe's recognition of faces of the same animal between different ages or between different orientations. Twelve adult sheep were first trained to discriminate between faces of two unfamiliar animals, one of which was associated with a food reward. Transfer of discrimination from this pair to the same pair but at a different age, or in a different orientation, was then evaluated (transfer test), and compared with a new pair of the same condition (control test). Learned discrimination of a frontal view of unfamiliar 3-month-old lambs' faces improved subsequent discrimination of the same pair when they were 1-month-old in comparison to discrimination of new 1-month-old faces. Moreover, sheep that were trained to discriminate frontal views of unfamiliar adult individuals discriminated profile views of the same animals more accurately than that of novels. However, learned discrimination of the profile view of unfamiliar adult faces had no effect on subsequent discrimination of the frontal view of that same pair. These results suggest that to some extent sheep recognise faces of unfamiliar animals at different ages and in different orientations.

Animals↗
PubMed2006

En2 knockout mice display neurobehavioral and neurochemical alterations relevant to autism spectrum disorder.

Autism spectrum disorder (ASD) is a prevalent and inheritable neurodevelopmental disorder. Recent human genetic studies are consistent with the homeobox transcription factor, ENGRAILED 2 (EN2), being an ASD susceptibility gene. En2 knockout mice (En2(-/-)) display subtle cerebellar neuropathological changes similar to what has been observed in the ASD brain. To investigate whether En2(-/-) mice displayed abnormal behavior relevant to ASD, they were monitored in tasks designed to assess social maturation as well as learning and memory. Deficits in social behavior were detected in En2(-/-) mice across maturation that included decreased play, reduced social sniffing and allogrooming, and less aggressive behavior. Deficits in two spatial learning and memory tasks were also observed. Because locomotor activity was a component of many of the behavioral tasks, this was measured at various stages of development. Locomotor activity was not compromised in the knockout. However, a more thorough analysis of motor behavior in En2(-/-) mice revealed deficits in specific motor tasks. To determine whether neurochemical changes were associated with these behavioral phenotypes, monoamine levels in specific brain regions were assessed. A cerebellar-specific increase in serotonin and its metabolite was observed. Interestingly, several reports have suggested that the serotonin pathway is affected in ASD. We conclude that En2(-/-) mice display behavioral and neurochemical changes, in addition to genetic and neuropathological changes, relevant to ASD. Therefore, these mice may be useful as an animal model of autism.

Aggression↗
PubMed2006

GABAB receptor antagonism abolishes the learning impairments in rats with chronic atypical absence seizures.

Chronic atypical absence seizures are a component of the Lennox-Gastaut syndrome, a disorder invariably associated with severe cognitive impairment in children. However, the cause of this intellectual delay remains unclear. The AY9944 model of chronic atypical absence seizures in rats reliably reproduces the electrographic, behavioral, pharmacological and cognitive features of clinical atypical absence. Using this model, we tested the hypothesis that the cognitive impairment associated with this disorder involves a gamma-aminobutyric acid B (GABA(B)) receptor-mediated mechanism. Therefore, we examined the effect of a specific, high affinity GABA(B) receptor antagonist, CGP35348, on the atypical absence seizures, the working memory deficits, and the altered long-term potentiation that we have observed in the AY9944 model. CGP35348 blocked atypical absence seizures, restored long-term potentiation to normal level, and reversed the cognitive deficit in the AY9944-treated animals. However, dose-response studies showed that lower doses of CGP35348 that failed to influence atypical absence seizure activity, completely reversed the spatial working memory deficit. These data suggest that GABA(B) receptor-mediated mechanisms are responsible for the cognitive dysfunction in the AY9944 model of chronic atypical absence seizures and further, that their cognitive impairment is independent of the seizure activity. The data raise the possibility that GABA(B) receptor antagonists may have therapeutic potential for the treatment of cognitive impairment in epilepsy syndromes where atypical absence seizures are a component.

Animals↗
PubMedDate not supplied

Atipamezole, an alpha(2)-adrenoceptor antagonist, has disease modifying effects on epileptogenesis in rats.

Stimulation of alpha(2)-adrenoceptors delays the development of kindling, a model of epileptogenesis in humans. Blocking alpha(2)-adrenoceptors is proconvulsant, but has beneficial effects on somatomotor recovery after experimental stroke. We investigated whether atipamezole, a selective alpha(2)-adrenoceptor antagonist, affects the recovery process from status epilepticus (SE)-induced brain damage, which affects the risk of epileptogenesis. Vehicle or atipamezole (100 microg/kg/h) treatment was started 1 week after the induction of SE and continued for 9 weeks using Alzet minipumps (n = 70). Development and severity of epilepsy, spatial and emotional learning, and histologic analysis were used as outcome measures. There were no differences in the percentage of animals with epilepsy in the different treatment groups. In the atipamezole group, however, daily seizure frequency was lower (P < 0.01), a higher percentage of epileptic animals had mild epilepsy (<1 seizure/day; P < 0.01), and seizure frequency did not increase over time compared with the vehicle group. The atipamezole group had milder hilar cell damage (P < 0.05) and less intense mossy fiber sprouting (P < 0.05). Behavioral impairments were similar between groups. Our data indicate that chronic treatment with atipamezole does not prevent epileptogenesis. There is, however, a disease-modifying effect; that is, the epilepsy that develops is milder and non-progressive. These data warrant further studies.

Adrenergic alpha-Agonists↗