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PubMed1998

Lateralized fascia dentata lesion and blockade of one hippocampus: effect on spatial memory in rats.

Unilateral blockade of the dorsal hippocampus by tetrodotoxin makes it possible to form lateralized spatial memories, which rapidly transfer to the naive hippocampus when training continues with intact brain. Unilateral X-ray irradiation of newborn rats causes irreversible destruction of granule cells in the ipsilateral fascia dentata (FD). Possible compensation of poor learning in the lesioned hemisphere by commissural transfer of memories from the intact hippocampus was examined in seven rats with unilateral FD lesion, which were first trained in the Morris water maze to asymptotic performance (mean escape latency 6+/-1 s). Subsequent testing during functional ablation either of the intact or of the lesioned hippocampus by tetrodotoxin revealed escape latencies 35+/-8 s or 8+/-1 s, respectively. Probe trial tests during inactivation of the intact and lesioned hippocampus showed target quadrant preference of 32+/-2% or 54+/-3%, respectively. The results indicate: (a) that one intact hippocampus alone can support the water maze task, (b) that no, or only a very weak, memory trace is available in the lesioned hippocampus. It is concluded that the above results are due to the inability of the FD lesioned hippocampus to process the information received from the ipsilateral entorhinal cortex.

Animals↗
PubMed2006

Effects of daily environmental enrichment on memory deficits and brain injury following neonatal hypoxia-ischemia in the rat.

Environmental enrichment (EE) results in improved learning and spatial memory, as well as attenuates morphological changes resulting from cerebral ischemia in adult animals. This study examined the effects of daily EE on memory deficits in the water maze and cerebral damage, assessed in the hippocampus and cerebral cortex, caused by neonatal hypoxia-ischemia. Male Wistar rats in the 7th postnatal day were submitted to the Levine-Rice model of neonatal hypoxia-ischemia (HI), comprising permanent occlusion of the right common carotid artery and a period of hypoxia (90 min, 8%O(2)-92%N(2)). Starting two weeks after the HI event, animals were stimulated by the enriched environment (1h/day for 9 weeks); subsequent to the stimulation, performance of animals in the water maze was assessed. HI resulted in spatial reference and working memory impairments that were completely reversed by EE. Following the behavioral study, animals were killed and the hippocampal volume and cortical area were estimated. There was a significant reduction of both hippocampal volume and cortical area, ipsilateral to arterial occlusion, in HI animals; environmental stimulation had no effect on these morphological measurements. Presented data indicate that stimulation by the daily environmental enrichment recovers spatial memory deficits caused by neonatal hypoxia-ischemia without affecting tissue atrophy in either hippocampus or cortex.

Analysis of Variance↗
PubMed1998

Acute blockade of hippocampal glucocorticoid receptors facilitates spatial learning in rats.

Corticosteroids can facilitate or impair learning and memory processes. We found that the glucocorticoid receptor antagonist RU38486 injected locally into the dorsal hippocampus dose-dependently improved the performance of male Wistar rats in the water maze 24 h after treatment. This observation suggests a discrete specificity of hippocampal glucocorticoid receptors in facilitation of memory.

Animals↗
PubMed1997

Reversal of scopolamine-induced deficits in navigational memory performance by the seed oil of Celastrus paniculatus.

Celastrus paniculatus (CP), a medicinal plant from India has been reputed to be useful as a pharmaceutical aid for learning and memory. We investigated the effects of the seed oil of CP on the 6 day performance of young adult rats in a navigational memory task-the Morris water maze. Chronic oral (gavage) daily treatment with CP. (50, 200, or 400 mg/kg) for 14 days completely reversed the scopolamine (0.5 mg/kg)-induced task performance deficit. On the other hand, acute treatment (single injection prior to scopolamine treatment) with CP (200 mg/kg) did not significantly reverse the scopolamine-induced impairment in maze performance. Alone, CP produced a slight, but significant improvement in maze performance on the first day of testing. Acute treatment or chronic 14 day treatment with CP resulted in no significant alteration in normal locomotor activity in an open field. Moreover, CP did not alter the scopolamine-induced increases in locomotor activity. Chronic treatment with CP did not alter brain acetylcholinesterase levels and no signs of cholinergic overstimulation were ever noted during or after treatment. Thus, the seed oil of CP, when administered chronically, selectively reversed the impairment in spatial memory produced by acute central muscarinic receptor blockade, supporting the possibility that one or more constituents of the oil may offer cognitive enhancing properties. The neural mechanism underlying the reversal of scopolamine's mnemonic effects by CP is not yet known, but it is not related to an anticholinesterase-like action.

Acetylcholinesterase↗
PubMed2000

A model of hippocampally dependent navigation, using the temporal difference learning rule.

This paper presents a model of how hippocampal place cells might be used for spatial navigation in two watermaze tasks: the standard reference memory task and a delayed matching-to-place task. In the reference memory task, the escape platform occupies a single location and rats gradually learn relatively direct paths to the goal over the course of days, in each of which they perform a fixed number of trials. In the delayed matching-to-place task, the escape platform occupies a novel location on each day, and rats gradually acquire one-trial learning, i.e., direct paths on the second trial of each day. The model uses a local, incremental, and statistically efficient connectionist algorithm called temporal difference learning in two distinct components. The first is a reinforcement-based "actor-critic" network that is a general model of classical and instrumental conditioning. In this case, it is applied to navigation, using place cells to provide information about state. By itself, the actor-critic can learn the reference memory task, but this learning is inflexible to changes to the platform location. We argue that one-trial learning in the delayed matching-to-place task demands a goal-independent representation of space. This is provided by the second component of the model: a network that uses temporal difference learning and self-motion information to acquire consistent spatial coordinates in the environment. Each component of the model is necessary at a different stage of the task; the actor-critic provides a way of transferring control to the component that performs best. The model successfully captures gradual acquisition in both tasks, and, in particular, the ultimate development of one-trial learning in the delayed matching-to-place task. Place cells report a form of stable, allocentric information that is well-suited to the various kinds of learning in the model.

Animals↗
PubMed1998

Spatial learning and memory induce up-regulation of nitric oxide-producing neurons in rat brain.

Changes of nitric oxide (NO)-producing neurons in the brain following learning is not yet clear. In present study, nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry and neuronal NO synthase (nNOS) immunohistochemistry were used to detect NOS neurons in rat brain. Results demonstrated that expression of NOS neurons in dentate gyrus and frontal cortex was significantly increased after a water-rewarded spatial alternation task when compared with that after sham training. The elevated expression of NOS neurons occurred not only in the earlier memory stage, but also in the later memory stage. In addition, the expression location and cell counts of NOS neurons in dentate gyrus and frontal cortex with NADPH-d staining or nNOS immunoreactivity resembled each other, but the cell counts of NADPH-d positive neurons were a little more than those of nNOS immunoreactive neurons. The involvement of NO in the processes of spatial learning and memory is further suggested.

Animals↗
PubMed2000

Experimental evidence for spatial learning on octopuses (octopus bimaculoides).

Octopuses forage far from temporary home dens to which they return for shelter. Spatial tasks may assess learning. Octopuses (Octopus bimaculoides) were placed in a novel arena, and their movements were tracked for 72 hr. Movements around the arena decreased across time, consistent with exploratory learning. Next, octopuses were given 23 hr to move around an arena; after a 24-hr delay, their memory of a burrow location was tested. Most remembered the location of the open burrow, demonstrating learning in 1 day. Finally, octopuses were trained to locate a single open escape burrow among 6 possible locations. Retention was tested after a week and was immediately followed by reversal training (location rotated 180 degrees ). Octopuses learned the original location of the burrow, remembering it for a week. Path lengths increased significantly after reversal, gradually improving and showing relearning. Octopuses show exploratory behavior, learning, and retention of spatial information.

Animals↗
PubMedDate not supplied

Interactive effects of prenatal cocaine and nicotine exposure on maternal toxicity, postnatal development and behavior in the rat.

Two experiments were performed to investigate the interactive effects of prenatal coadministration of cocaine hydrochloride (C) and nicotine tartrate (N). Experiment I was designed to determine doses of C and N that could be coadministered without altering maternal gestational parameters and/or fetal viability. Exposure of Sprague-Dawley rats to combined high-dose C (20 mg/kg) and high-dose N (5.0 mg/kg) on gestation days 8-21 was not more toxic to dam or fetus that that of exposure to C alone. Experiment II investigated pregnancy outcome, postnatal development, and behavior of the offspring following drug exposure to either high-dose cocaine (20 mg/kg: CS), high-dose nicotine (5.0 mg/kg: NS), or both (NC) on gestation days 8-21. N was administered by osmotic minipump and C by sc injection. Saline-injected dams, fitted with saline-fitted pumps (SS), and untreated dams, pair-fed (PF) to NC females, served as controls. Alterations in maternal variables were limited to a 10-15% decrease in food consumption in NC and CS groups. Pregnancy outcome and birth statistics were unaffected by prenatal treatment, as was offspring body weight during the first four postnatal weeks. However, the development of surface righting was delayed inC CS pups, and only CS offspring were underresponsive to the stimulatory effects of dopamine agonists on activity and stereotypy. Behavioral responses to N challenge were similar in all groups. In addition, only CS offspring showed altered behavioral responses in a spontaneous alternation task. Treatment effects on dopamine D1 and D2 binding in the caudate nucleus were not observed. The combination of N and C did not exacerbate any of the behavioral changes seen in CS offspring. These results support the hypothesis that C is a behavioral teratogen in rodents, and suggest that in the present model, nicotine can mitigate some of the consequences of in utero exposure to cocaine.

Aging↗
PubMed2003

Castration in rats impairs performance during acquisition of a working memory task and exacerbates deficits in working memory produced by scopolamine and mecamylamine.

RATIONALE: Although much research has focused on the effects of ovarian hormones on learning and memory in females, less information is available regarding the effects of testicular hormones on learning and memory in males. Additionally, despite evidence of an interaction of testicular hormones and the cholinergic system in areas of the brain implicated in learning and memory, no information is available regarding the behavioral consequences of that interaction. OBJECTIVES: We assessed the effect of castration in male rats on working memory during acquisition of a radial maze. We also assessed the interactive effects of castration and scopolamine, a muscarinic receptor antagonist, as well as mecamylamine, a nicotinic receptor antagonist, on behavior. METHODS: Young adult male rats were castrated or underwent sham surgeries. Beginning 10 days after surgeries, performance on a task of working memory was assessed across 24 days of acquisition in an eight-arm radial maze. Following acquisition, scopolamine and mecamylamine dose-effect curves were established. RESULTS: Castration of male rats significantly decreased arm-choice accuracy during acquisition. Castration significantly exacerbated impairments in arm-choice accuracy produced by scopolamine as well as mecamylamine, without altering the disruptive effects of the drugs on the rate at which rats entered the arms of the maze. CONCLUSIONS: These results indicate that castration in male rats impairs working memory during acquisition of a spatial maze task. Additionally, these results suggest that the absence of testicular hormones increases the sensitivity of male rats to the impairing effects of scopolamine as well as mecamylamine on working memory.

Animals↗
PubMed2006

Improved spatial recognition memory in mice lacking adenosine A2A receptors.

Adenosine receptors play an important role in learning and memory as their antagonists have been found to facilitate learning and memory in various tasks in rodents. However, few studies have examined the effect of adenosine A2A receptor deficiency on cognition. In the present study, we therefore used the Y-maze, a simple two-trial recognition test to measure spatial recognition memory in mice lacking adenosine A2A receptors. The results showed that adenosine A2A receptor knockout mice had a higher percentage of novel arm visits as first choice than wild-type CD1 mice. Moreover, these mice showed longer duration of visits in the novel arm when compared with controls, suggesting that the lack of adenosine A2A receptors improved spatial recognition memory. On the other hand, mice lacking the adenosine A2A receptors had low scores in the number of arm visits, suggesting that they were hypoactive. In conclusion, these data suggest the involvement of adenosine receptors in modulating spatial recognition memory in mice, consistent with earlier findings using adenosine receptor antagonists.

Analysis of Variance↗
PubMed2005

Exploratory activity and spatial learning in 12-month-old APP(695)SWE/co+PS1/DeltaE9 mice with amyloid plaques.

APP(695)SWE/co+PS1/DeltaE9 mice with Abeta plaques in neocortex and hippocampus were evaluated in tests of exploratory activity and spatial learning. On the initial testing day, 12-month-old APP(695)SWE/co+PS1/DeltaE9 mice spent more time than non-transgenic controls in the open arms of the elevated plus-maze. The bigenic group also travelled farther in the central region of the open-field without spending more time there. Only the bigenic group alternated above chance in the T-maze. In the Morris water maze, APP(695)SWE/co+PS1/DeltaE9 mice were impaired during acquisition of the hidden platform sub-task and the probe trial but not in the visible platform test. These results indicate a selective spatial deficit and disinhibitory tendencies in a mouse model with amyloid pathology.

Amyloid beta-Protein Precursor↗
PubMed1994

Differential effects of serotonin and raphe grafts in the hippocampus and hypothalamus: a combined behavioural and anatomical study in the rat.

Combined with a partial cholinergic deficiency, serotonergic lesions induce severe spatial learning deficits. Serotonergic lesions, however, have additional effects, such as reduced body weight and disruption of thermoregulation, which may be the cause of the observed learning deficits. Restoration of the serotonergic innervation of the hippocampus by raphe grafts reduces these learning deficits. The effects of the grafts may result from a direct support of spatial learning but may also be an indirect result of preventing some of the other effects of serotonergic lesions. In the present study we used raphe grafts to examine the selectivity and specificity of the effects of serotonergic lesions in the rat, and used the behavioural effects as an indication of successful transplantation in order to examine the fine details of such grafts. Raphe grafts in the hippocampus did not prevent the effects of the lesions on body weight, thermoregulation and exploratory behaviour but did minimize the effects of the lesions on spatial learning. In contrast, raphe grafts in the hypothalamus reduced the effects of the lesions on thermoregulation but failed to support learning. The grafted fibres showed termination specificity with the interneurons, which is typical of the serotonergic innervation of the normal hippocampus. The results indicate that the serotonergic innervation of the hippocampus functions locally to support spatial learning. This role of serotonin is independent of its involvement in modulation of body weight, thermoregulation or exploratory behaviour. The results confirm that the modes of serotonergic action in the hippocampus include the selective innervation of specific interneuron subpopulations.

5,7-Dihydroxytryptamine↗
PubMed1992

Choice behavior of fornix-damaged rats in radial maze error-free situations and subsequent learning.

Fornix-damaged, sham-operated, and control rats were placed in a radial eight-arm maze for fixed series of runs with either a 0% or a 100% reinforcement schedule in order to study their choice behavior independently from any learning problem. Subsequently, the ability to learn the radial maze task was examined as a function of the exploratory patterns developed in each error-free situation. The results showed that the continuous absence or presence of food in the radial maze induced two distinct models of exploration in sham-operated and control rats: choice alternation in the absence of food and perseveration in the presence of food. Conversely, this dichotomy did not occur in fornix-damaged rats that run approximately the same number of paths in both error-free situations, but made fewer different path choices in the 0% reinforcement condition and more different path choices in the 100% reinforcement condition than controls. When submitted to the radial maze task, a positive transfer was observed in all groups from the error-free situation in which the rats run more different paths: from the 0% reinforcement situation for controls and from the 100% reinforcement situation for the lesioned rats. These data indicate that damaging the septo-hippocampal pathway modifies spontaneous choice behavior through a different response to specific reinforcement programs but does not prevent the memorization and the transfer of information from error-free to learning situations.

Animals↗
PubMed1999

Influence of acute and repeated interleukin-2 administration on spatial learning, locomotor activity, exploratory behaviors, and anxiety.

Interleukin-2 (IL-2), released from activated T cells, influences central neurochemical functioning, and IL-2 immunotherapy in cancer patients may provoke neuropsychiatric and cognitive disturbances. In this study, acute, systemic IL-2 did not influence Morris water-maze performance in mice. In contrast, chronic IL-2 impaired performance when the position of the escape platform varied over days but was without effect when the platform position was fixed. These effects could not be attributed to illness, because IL-1beta, which induces marked malaise, did not influence water-maze performance. Chronic IL-2 produced modest reductions in exploration and approach to a novel stimulus, effects not seen after acute treatment, but did not influence spontaneous alternation performance or behavior in an elevated plus-maze test. Thus, repeated IL-2 may influence spatial working memory without affecting habituation/ attentional processes or anxiety.

Animals↗
PubMed1999

Effects of nucleotides on learning and memory in a Morris water maze test in normal and basal forebrain-lesioned rats.

The effects of nucleotides on learning and memory were studied in normal and basal forebrain-lesioned rats using a Morris water maze test. Chronic oral administration of a nucleotide mixture (500 mg/kg), containing an equal weight of the disodium salts of adenosine 5'-monophosphate, guanosine 5'-monophosphate, inosine 5'-monophosphate, cytidine 5'-monophosphate, and uridine 5'-monophosphate facilitated learning acquisition in normal rats. In basal forebrain-lesioned rats, administration of the nucleotide mixture showed a tendency to improve learning acquisition and memory retrieval. In the biochemical studies, no significant changes were observed in brain choline and acetylcholine levels by treatment with the nucleotide mixture at the doses tested in both normal and basal forebrain-lesioned rats. The nucleotides did not affect the monoaminergic systems in normal rats, but did cause some changes in these systems in basal forebrain-lesioned rats. The present studies indicate that nucleotides ameliorate learning and memory processes in normal rats, but not in basal forebrain-lesioned rats, and they also modulate the activity of the central monoaminergic systems under certain conditions.

Acetylcholine↗
PubMed1999

A behavioral and neuroanatomical assessment of an inbred substrain of 129 mice with behavioral comparisons to C57BL/6J mice.

The inbred 129 substrains have been characterized as poor learners that display hypoplasia of the corpus callosum. However, they are used extensively as a source of embryonic stem (ES) cells for creating mice carrying altered copies of a targeted gene ('knockout mice'). The present research investigated callosal agenesis and behavior in the 129/SvEvTac substrain and compared their behavior to that of C57BL/6J mice. In addition, the degree to which callosal agenesis affected behavior was assessed. Nearly 80% of 129/SvEvTac mice in the current sample exhibited callosal hypoplasia, although this was not subsequently found to be associated with any measure of cognition. They learned the Morris maze and a non-spatial pattern discrimination task, though at a level inferior to C57BL/6J mice. They were unable to learn shuttlebox avoidance or the Lashley III maze. The only measure on which they performed better than C57BL/6J mice was a simple water escape task. Thus, 129/SvEvTac mice, in addition to displaying aberrant neuroanatomy, perform poorly on many behavioral tasks, resulting in potential interpretational difficulties.

Agenesis of Corpus Callosum↗