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Retrosplenial cortex lesions of area Rgb (but not of area Rga) impair spatial learning and memory in the rat.

The retrosplenial cortex, which is situated in a critical position in the flow of information between the hippocampal formation and the neocortex, contributes to spatial memory, but no studies have examined the distinct contribution of each area of the retrosplenial cortex to this behavior. This study tests the hypothesis that the two areas of the retrosplenial granular cortex play distinct roles in spatial learning and memory. Adult, male Sprague-Dawley rats with small, bilateral lesions (ibotenic acid) of the retrosplenial granular cortex were tested for 2 weeks in a repeated acquisition water maze task. Compared to controls, rats with complete lesions of the retrosplenial granular b cortex (Rgb) were slightly, but significantly impaired, whereas rats with lesions of the retrosplenial granular a cortex (Rga) displayed no impairment. Further, the Rgb-lesioned (but not the Rga-lesioned) group was impaired in the probe trials at the end of the first week of training. All animals were tested in the same paradigm for a second week to determine if the learning and memory impairment in the Rgb-lesioned rats simply reflected "delayed learning." All animals improved their maze performance during the second week of testing, but the Rgb-lesioned group still had no preference for the correct quadrant in the probe trial. Together, these data indicate that Rgb plays a small, independent role in spatial learning and memory. Further, although selective lesions of Rga or Rgb do not cause a large deficit in learning, concomitant destruction of both areas causes a much greater impairment in learning than would be predicted from their independent contributions. The data highlight the unique and complex contribution of each area of the retrosplenial cortex to behavior.

Animals↗

Total body 4.5 Gy gamma irradiation-induced early delayed learning and memory dysfunction in the rat.

In an attempt to determine the consequences of total body radiation damage on learning and memory in the rat, twenty-eight male Wistar rats aged 4 months received 4.5 Gy total body gamma-irradiation (TBI) while 28 rats received sham irradiation. Sequential behavioral studies of negative reinforcement including a/ one- and b/ two-way avoidance tasks were undertaken. a/ One-way avoidance test: this test was performed before and after TBI. Prior to irradiation both groups were similar. At 20 days (D) and at 3 months post-TBI, irradiated rats had a significantly lower percentage of avoidance than controls but no statistical difference was found at 5 months post-TBI. b/ Two-way avoidance test: this test was performed only after TBI. At days 21, 22, 23, 24, (leaming) and at 4 or 6 months (recalls) post-TBI the mean percentage of avoidance was significantly lower in irradiated than in control rats. This study demonstrates that total-body exposure to 4.5 Gy gamma-irradiation induces behavioral dysfunction affecting learning and transitorily memory. These results suggest that a relatively low dose of total body irradiation can induce neurological complications, which persist 4-6 months later.

Animals↗

The effects of neonatal choline dietary supplementation on adult spatial and configural learning and memory in rats.

The facilitative effects of pre- and early postnatal choline chloride dietary supplementation on adult rat spatial and nonspatial learning and memory were examined using a delayed match-to-place and a transverse-patterning discrimination task. Animals were exposed to the choline supplementation both prenatally (through the diet of pregnant rats) and postnatally (subcutaneous injection) for 24 days. In the first experiment, 90-day-old rats were given pairs of trials in which they first found a hidden platform in a Morris water maze in a particular location (acquisition trials), and then were required to remember that position 10 min later (test trials). Those animals given neonatal choline pretreatment found the platform on test trials significantly faster than did animals in a saline-treated control group. All animals were subsequently tested in the same paradigm following atropine sulfate injections. The atropine eliminated the difference between experimental and control animals on test trials. In a second experiment, neonatally treated choline rats performed significantly better than controls in acquiring a visual transverse patterning discrimination task previously found to be sensitive to hippocampal and/or frontal damage. The present study extends the description of long-term functional enhancement produced by perinatal choline supplementation to include the ability to use and remember visual configural associations, working spatial memory, and to relate these effects to modifications in cholinergic basal forebrain systems.

Age Factors↗

Effect of fluoxetine on learning and memory involves multiple 5-HT systems.

Diverse evidence suggests that 5-HT uptake blockers enhance learning and memory. However, there is no information about the mechanisms of action involved in such effects. The aim of the present work was to investigate the nature of the receptors involved in the effects of fluoxetine on learning. Therefore, a dose-response curve of posttraining injection (intraperitoneal) of fluoxetine was carried out in an associative learning task (auto-shaping). Fluoxetine or the vehicle was injected 10 min after 5-HT antagonists: (+/-)-pindolol, (+/-)-propanolol, NAN-190, ketanserin, ritanserin, mesulergine, MDL 72222, or SDZ 205-557. Presynaptic activity was eliminated by means of chloroamphetamine pretreatment. Scopolamine (an anticholinergic) and dizocilpine (a noncompetitive NMDA receptor antagonist) were also used. Results showed that fluoxetine enhanced learning of the conditioned response (CR) in a dose-dependent fashion. All 5-HT antagonists had no effects by themselves but inhibited the effects of fluoxetine at different degrees. Decrement of CR produced by scopolamine was reversed by fluoxetine. Dizocilpine did not affect CR but prevented the effects of fluoxetine. The present findings suggest that the actions of fluoxetine on learning are due to an interaction with multiple receptors of postsynaptic nature.

Animals↗

Acceleration after-effects on learning and memory in rats: +10 Gz or +6 Gz for 3 min.

High sustained positive Gz (+Gz) exposures have been shown to have a pathophysiological impact on the brain in rats. However, the consequence for brain function such as learning and memory remains elusive. In the present study, we investigated locomotor activity, learning ability and memory in rats over 6 days (d) following +6 Gz/3 min and +10 Gz/3 min exposures. In an open field test, rats treated with +10 Gz showed a significant increase in the time spent in the center square immediately and 2d after exposure compared with control rats. In contrast, the number of grid crosses and number of rears of rats decreased significantly immediately after +6 Gz and +10 Gz exposures. In addition, a Y-maze test revealed that +Gz exposures reduced the number of correct responses and increased total reaction time in rats, and the number of correct responses was negatively correlated with the total reaction time in all groups throughout the period of study. Moreover, the passive avoidance test exhibited that the latency increased significantly on 0 d and decreased significantly on 6 d after +Gz exposures compared with control. Thus, +6 Gz/3 min and +10 Gz/3 min exposures may transiently decrease locomotor activity, impair learning, and induce a deficit in memory retention in rats.

Acceleration↗

Impaired learning and memory in OLETF rats without cholecystokinin (CCK)-A receptor.

Cholecystokinin (CCK) is one of the most abundant neurotransmitter peptides in the brain. As OLETF rats lack CCK-A receptor because of a genetic abnormality, we examined whether learning and memory were impaired in these animals using an elevated eight-arm radial maze. After the completion of a radial maze study, the animals were sacrificed for histological examination of the brain. In some animals, long-term potentiation (LTP) in the hippocampus was measured. In the radial maze, the level of activity (seconds/entry) and the time remaining in the arms were significantly longer in OLETF rats. The number of errors was also significantly higher, and that of the correct choices was significantly lower in OLETF rats compared to the controls (LETO rats). The LTP of the population spike was significantly lower in the OLETF than in the LETO rats. No histological abnormalities were observed. From these observations, we concluded that learning and memory functions were impaired in the OLETF rats.

Animals↗

Effects of an acidic fibroblast growth factor fragment analog on learning and memory and on medial septum cholinergic neurons in senescence-accelerated mice.

We examined the effects of repeated subcutaneous injections of an acidic fibroblast growth factor fragment analog, [Ala16] acidic fibroblast growth factor (1-29), on learning and memory and on the choline acetyltransferase immunoreactivity of forebrain neurons in senescence-accelerated mice. One group of accelerated senescence-prone mice (accelerated senescence-prone-8) received [Ala16] acidic fibroblast growth factor (1-29), whereas the other group of accelerated senescence-prone-8 mice and a group of accelerated senescence-resistant mice (control) received vehicle solution. Injections began at three weeks after birth and were given weekly for 10 months. In a passive avoidance test, the mean retention latency at three, six and nine months of age was significantly longer in controls (vehicle-treated accelerated senescence-resistant-1) and acidic fibroblast growth factor fragment-treated accelerated senescence-prone-8 than in vehicle-treated accelerated senescence-prone-8 mice, and the latency in acidic fibroblast growth factor fragment-treated accelerated senescence-prone-8 mice was significantly shorter than that in controls only at nine months of age. In the Morris water maze task, the mean latency to climb onto the platform was significantly longer in acidic fibroblast growth factor fragment- and vehicle-treated accelerated senescence-prone-8 mice than in controls. However, the mean latency in the third and fourth trial blocks was significantly shorter for acidic fibroblast growth factor fragment-treated accelerated senescence-prone-8 than for vehicle-treated accelerated senescence-prone-8 mice. In the probe trials, controls and acidic fibroblast growth factor fragment-treated accelerated senescence-prone-8 mice spent significantly more time in the quadrant in which the platform had previously been located than in the other three quadrants. In acidic fibroblast growth factor fragment-treated accelerated senescence-prone-8 mice, the density of medial septum neurons intensely stained for choline acetyltransferase was significantly greater than that in vehicle-treated accelerated senescence-prone-8 mice, but significantly less than that in controls. The results indicate that the beneficial effect of [Ala16] acidic fibroblast growth factor (1-29) on learning and memory function in accelerated senescence-prone-8 mice may be related to a preservation of function in medial septum cholinergic neurons.

Aging↗

[Effect of selenium deficiency on the F344 inbred line offspring rats' neuro-behavior, ability of learning and memory].

OBJECTIVE: To establish the selenium (Se) deficient animal model on F344 inbred line rats and observe the effects of a long-term Se-deficiency on the offspring's neuro-behavior, abilities of learning and memory. METHODS: Feeding F344 inbred line rats on Se-deficient diet to establish Se-deficient animal model. For the offspring, the body weight, physiological indexes nervous reflections for growth and development were monitored during the early postnatal period. RESULTS: The Se-deficient diet contained less than 0.01 mg/kg and the glutathione peroxidase (GSH-Px) activity in blood of the Se-deficient group rats is lower than the Se-normal group after feeding on Se-deficient diet for 4 weeks. For the offspring, the birth weight and the body weight of Se-deficient group were obviously lower than the Se-normal group before weaning. Se-deficient offspring rats differed from Se-normal controls in lower scores in surface righting reflex (RR) test at postnatal 4th day after delivery, cliff avoidance test at postnatal 7th day and auditory acuity trial at postnatal 10th day respectively. But these differences disappear after a few days in the same tests. In addition, no significant differences between two groups in suspending test and walking ability test at postnatal 12th and 14th day. In open field test, Se-deficient male offspring stayed less time in the middle grid and moved less. In Morris water maze test, the Se-deficient offspring spent more time to find the hidden platform at the 6th and 9th training tests in the place navigation trial. Furthermore, the Se-deficient group spent less time in target quadrant when giving the spatial probe trial. CONCLUSION: A Se-deficient animal model have been established on F344 inbred line rats successfully. A long-term Se deficiency could retard the development of the offspring in uterus and after delivery. Se deficiency also decreased the offspring's abilities of spatial learning and memory in Morris water maze test and resulted in the male offspring's nervousness to new stimulant.

Animals↗

Influence of opioid peptides on learning and memory processes in the chick.

Several experiments were conducted to examine the effects of intracranial injection of opioid peptides and antagonists on learning and memory in the chick. Pretraining injection of [leu5]enkephalin and the selective delta receptor agonist [D-Pen2,L-Pen5]enkephalin (DPLPE) into the intermediate medial hyperstriatum ventrale (IMHV) produced impairment. ICI 174,864, a delta-selective antagonist, reversed the impairment produced by either [leu5]enkephalin or DPLE, results indicating that delta receptors may play a role in learning in the chick and suggesting that the impairment produced by [leu5]enkephalin is mediated through delta opioid receptors. beta-endorphin produced a naloxone-reversible impairment in performance, which suggests that this impairment is mediated by opioid receptors. Bilateral injection of beta-endorphin into the IMHV produced impairment, as did unilateral injection into the right, but not left, IMHV. Only bilateral injections into IMHV of [leu5]enkephalin were effective. These results suggest that the effects of beta-endorphin are centrally mediated whereas the effects of [leu5]enkephalin may be localized to other brain regions or are peripherally mediated. These initial results suggest that opioids are associated with learning and memory in the chick.

Animals↗

Hepatocyte growth factor improved learning and memory dysfunction of microsphere-embolized rats.

Hepatocyte growth factor (HGF), an organotropic factor for regeneration and protection in various organs, has the ability to attenuate cerebral ischemia-induced cell death. The effect of HGF on learning and memory function after cerebral ischemia, however, remains unknown. We have demonstrated that administration of human recombinant HGF (hrHGF) into the ventricle reduced prolongation of the escape latency in acquisition and retention tests of the water maze task on Days 12-28 after microsphere embolism-induced cerebral ischemia. Treatment with hrHGF also attenuated the decrease in viable area and the density and number of perfused cerebral vessels, particularly those with a diameter smaller than 10 microm, of the ipsilateral hemisphere on Day 28 after the cerebral ischemia. We observed that treatment with hrHGF reduced the number of TUNEL-positive cerebral endothelial cells at the early stage after the ischemia. These results suggest that hrHGF prevents learning and memory dysfunction seen after sustained cerebral ischemia by protecting against injury to the endothelial cells. HGF treatment may be a potent therapeutic strategy for cerebrovascular diseases, including cerebral infarct and vascular dementia.

Analysis of Variance↗

Differential contributions of dopaminergic D1- and D2-like receptors to cognitive function in rhesus monkeys.

RATIONALE: Dopaminergic neurotransmission is critically involved in many aspects of complex behavior and cognition beyond reward/reinforcement and motor function. Mental and behavioral disorders associated with major disruptions of dopamine neurotransmission, including schizophrenia, attention deficit/hyperactivity disorder, Parkinson's disease, Huntington's disease, and substance abuse produce constellations of neuropsychological deficits in learning, memory, and attention in addition to other defining symptoms. OBJECTIVE: To delineate the role dopaminergic D1- and D2-like receptor subtypes play in complex brain functions. MATERIALS AND METHODS: Monkeys (N = 6) were trained on cognitive tests adapted from a human neuropsychological assessment battery (CAmbridge Neuropsychological Test Automated Battery). The battery included tests of spatial working memory (self-ordered spatial search task), visuo-spatial associative memory and learning (visuo-spatial paired associates learning task, vsPAL) and motivation (progressive ratio task, PR). Tests of motor function (bimanual motor skill task, BMS; rotating turntable task, RTT) were also included. The effects of the dopamine D2-like antagonist raclopride (10-56 microg/kg, i.m.) and the D1-like antagonist SCH23390 (SCH, 3.2-56 microg/kg, i.m.) on cognitive performance were then determined. RESULTS: Deficits on PR, RTT, and BMS performance were observed after both raclopride and SCH23390. Spatial working memory accuracy was reduced to a greater extent by raclopride than by SCH, which was unexpected, given prior reports on the involvement of D1 signaling for spatial working memory in monkeys. Deficits were observed on vsPAL performance after raclopride, but not after SCH23390. CONCLUSIONS: The intriguing results suggest a greater contribution of D2- over D1-like receptors to both spatial working memory and object-location associative memory.

Animals↗

[Learning and memory: traditional and systemic approach].

The same empiric event may appear as different facts for authors adhering to different theories. The present work was designed with analyze learning and memory from the viewpoint of systemic approach and to compare this view with the traditional one. Neuron's activity is considered not as a response to synaptic inflow that ensures the conduction of excitation but as means of changing the relation with environment, "action" that helps eliminate the discrepancy between cell's needs and its microenvironment. It is suggested that learning and memory consolidation is based not on a consistent increase in efficacy of synaptic transmission in neuronal chains but on systemogenesis--establishment of new systemic specializations of neurons not necessarily linked directly through synapses. The article discusses the role of systemogenetic processes taking place in normal as well as in pathological state: selection, reconsolidational modifications of previously formed memory store, genes activation, neurogenesis and apoptosis. The systemic understanding of the phenomenon of long-term potentiation is-substantiated. Finally, the scheme is suggested describing variants and stages of memory store formation.

Animals↗

[Expression of immediate-early genes c-fos and c-jun in the marginal division of striatum during learning and memory].

OBJECTIVE: To study the expression of immediate-early genes c-fos and c-jun in the marginal division (MrD) of rat striatum during learning and memory. METHODS: After Y-maze training in rats, the expression of immediate-early genes c-fos and c-jun in the MrD was investigated immunocytochemically. RESULTS: After 1 h of Y- maze training, the expression of c-Fos and c-Jun proteins was significantly enhanced in the MrD, where c-Jun protein in particular was more intensely expressed than in other parts of the striatum. The training group showed significantly higher expressions of the 2 proteins than pseudotraining group (P<0.01). In addition, positive expression was also observed in the hippocampus, cingulum cortex and other parts of the brain. CONCLUSION: Immediate-early genes c-fos and c-jun in the MrD participate in the signal transduction during learning and memory processes in the courses of Y-maze training of the rats.

Animals↗

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↗

The effect of subchronic administration of vigabatrin on learning and memory in nonepileptic rats.

The present experiments investigated whether subchronic administration of vigabatrin, a GABA-mimetic drug, affects the performance of normal rats in the behavioural tasks assessing learning and memory. The effects of vigabatrin [50-200 mg/kg (IP)/day] administration on the acquisition and retention of water maze and passive avoidance task were studied. According to the results of three experiments, vigabatrin treatment did not markedly impair the acquisition or retention of water maze task. Furthermore, vigabatrin-treated rats were not inferior to saline-treated rats in reversal learning of water maze task. On the other hand, vigabatrin treatment slightly increased the speed of swimming in rats. The administration of vigabatrin did not affect the performance (training latency, number of training trials, testing latency) of rats in the passive avoidance task. According to these results, the effects of vigabatrin, a new antiepileptic drug, on the performance of nonepileptic rats were modest in behavioural tasks used to assess learning and memory.

Amino Acids↗

Reductionism in learning and memory.

This chapter examines the successes and (at least for now) failures of reductionist approaches in dealing with the problem of learning and memory. Beginning with the work of Pavlov on classical conditioning and the theoretical work of Hebb, the paper traces the contributions made by studies on Aplysia, Drosophila and long-term potentiation in the mammalian hippocampus.

Animals↗

[Chronic pain impairs spatial learning and memory ability and down-regulates Bcl-2 and BDNF mRNA expression in hippocampus of neonatal rats].

OBJECTIVE: To investigate the effect and possible mechanism of complete Freund's adjuvant induced chronic pain on later function of learning and memory in neonatal rats. METHODS: Sixty Sprague-Dewley rat pups (10 litters of 6 pups) were randomly divided into control group and chronic pain group (n = 30 in each group). In the chronic pain group, left hind paws of the rats were treated with subcutaneous injection of 20 microl of CFA on postnatal day-2. The control rat pups received normal saline. The hippocampus of rats were separated on postnatal days 10 and 21 (one rat in each group from every litter, n = 10). The expression of Bcl-2 and BDNF mRNA were investigated by RT-PCR. Morris water maze tests were performed on day 21 (one rat in each group from every litter, n = 10). RESULTS: In hidden-platform training of Morris water maze, the mean escape latency of rats in the chronic pain group were longer than that of the control rats. In spatial probe tests, the average percentages of the swimming time and distances in the platform quadrant in the pain group rats were less than those in the control group. There was no significant difference in visible-platform training between the two groups. The Bcl-2 and BDNF mRNA expressions in hippocampus of the pain group rats were lower than those in the control at day 10, but no significant difference at day 21. CONCLUSION: Chronic pain stress induced by CFA impairs the spatial learning and memory function in neonatal rats. These effects might exert through down-regulating Bcl-2 and BDNF mRNA expression in the hippocampus.

Animals↗

Glucose treatment attenuates spatial learning and memory deficits of aged rats on tests of hippocampal function.

Groups of old and young rats were administered three tests of spatial learning and memory that are known to be sensitive to hippocampal dysfunction: the radial arm maze (RAM), spatial non-matching-to-sample (SNMTS), and a spatial vs. local cue-preference task. Old rats performed worse than young rats on the RAM and SNMTS tasks; on the cue-preference task, young rats were biased to use spatial cues, whereas old rats exhibited strong preferences for distinct, local cues. Peripheral injections of glucose (100 mg/kg) improved performance by old rats on the RAM and SNMTS, which correlated with measures of glucose metabolism. Glucose treatment did not affect old rats performance on the cue-preference task. There was evidence that glucose-treatment improved performance of young rats in the RAM test, but not the other tests. The results extend the range of tasks on which glucose-induced cognitive enhancement has been demonstrated in aged rats, and provides further evidence that memory loss resulting from hippocampal dysfunction is especially amenable to glucose treatment.

Aging↗