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PubMed2000

[Changes of learning and memory function under weightlessness or simulated weightlessness].

The work efficiency of astronauts has an intimate connection with the brain function state during space flight. The research results of the learning and memory mechanism of the brain in recent years were introduced. The effects of weightlessness or simulated weightlessness on brain's learning, memory, focused attention and many other higher neural activities and on the relative neural transmitters were summarized. Several research aspects were put forward in the future.

Aerospace Medicine↗
PubMed2006

Behavioral and electrophysiological studies of chronic oral administration of L-type calcium channel blocker verapamil on learning and memory in rats.

It has been shown that L-type voltage dependent calcium channels (VDCCs) have important role in learning and memory. In vivo and in vitro electrophysiological recordings of hippocampal neurons have demonstrated their involvement in long-term potentiation (LTP), which considers being one possible cellular mechanism underlying learning and memory. The long-term effect of VDCCs of hippocampal dentate gyrus (DG) so far on synaptic plasticity has not received much attention. In this study, the effect of chronic (60 days) oral administration of L-type calcium channel blocker verapamil on learning and memory and synaptic plasticity of hippocampal dentate gyrus in rats has been investigated. L-type calcium channel antagonist, verapamil chronically and orally at different doses (10, 20 and 50 mg/kg) was used to investigate learning and memory by passive avoidance learning. LTP in perforant-DG synapses was assessed (by either 200 or 400 Hz tetanization) in order to investigate long-term effect of verapamil on synaptic plasticity. In this case, field excitatory postsynaptic potential (fEPSP) slope and population spike (PS) amplitude were measured. Our behavioral study has shown that chronic oral treatment of verapamil has no effect on learning whereas verapamil (50 mg/kg) decreased memory retrieval. Verapamil (20 and 50 mg/kg) inhibited EPSP-LTP induction at 400 Hz but not at 200 Hz tetanization. Furthermore, only verapamil (50mg/kg) decreased PS-LTP with respect to control group. These data suggest that 400 Hz LTP is required for activation of L-type VDCCs and it seems that verapamil is more effective on L-type calcium channels of DG dendrites than their soma.

Administration, Oral↗
PubMed2003

Effects of ovariectomy and calcium deficiency on learning and memory of eight-arm radial maze in middle-aged female rats.

There is increasing evidence that estrogen and calcium ion are involved in learning and memory. In the present study, to examine the effect of estrogen deficiency and low-calcium diet on learning and memory, middle-aged female Wistar rats (50 weeks old) were fed either a low-calcium (0.02% Ca) or a normal-calcium (1.25% Ca) diet throughout the experiment. Rats were ovariectomized (OVX) or sham-operated (Sham). These animals were divided into four groups: 1) Sham group with normal-calcium diet [Sham-normal Ca group], 2) OVX group with normal-calcium diet [OVX-low Ca group], 3) Sham group with low-calcium diet [Sham-low Ca group], 4) OVX group with low-calcium diet [OVX-low Ca group]. Seventy-seven days after the OVX or Sham operation, the learning and memory abilities in the female rats were examined by using a radial maze task according to the method of Olton and Samuelson (regular trials) and using a delay-interposed task following regular trials. During regular trials and delay-interposed tasks, the OVX-low Ca group was inferior to all the other groups in accuracy of choice behavior. Both Sham-normal Ca and Sham-low Ca groups showed more accurate choices than the OVX-low Ca group, but were less accurate than the Sham-normal Ca group. In addition, there was no significant difference in locomotor activity between any of the groups. These results suggest that OVX or low-calcium diet may impair learning and memory, and that the combination of these factors impaired more markedly when the rats were tested in the eight-arm radial maze. These results may also imply the possibility that a woman in menopause or post-menopause suffers impairment of learning and/or memory when intakes low-calcium diet.

Age Factors↗
PubMed1986

Event-related potentials (ERPs) in a learning and memory test.

The present study outlines a new paradigm to investigate the effects of learning and memory on event-related potentials (ERPs). In the learning phase, subjects had to learn a sequence of 12 auditory consonant-vowel syllables. In the test phase, subjects had to detect and report a change in the learned sequence. Auditory ERPs were recorded from the frontal, vertex, and parietal midline positions. In the learning phase, an early negative effect (EN) and a P3 with a slow wave (SW) occurred for the learned syllables, whereas a pre-stimulus negativity (PSN) occurred prior to the syllables not yet learned. In the test phase, the PSN preceded both the replaced syllables and those presented in their old positions. The EN and an N2-P3 complex were elicited by the replaced syllables, the EN by the syllables presented in their old positions. It was concluded that the ERPs can display specific effects related to cognitive processes underlying learning and memory. The PSN was suggested to reflect the expectation of the stimuli, the EN the activation of a template and the rehearsal of the stimuli. The SW was suggested to be related to a template match process with the learned syllables. The N2, elicited by the replaced stimuli, could imply a cognitive template mismatch and the P3 with the SW the updating of working memory.

Adult↗
PubMed1988

[Pharmacological studies on Y-8894. (VIII). Effects on learning and memory in the radial maze task in mice].

Effects of Y-8894 on learning and memory were studied using a radial maze task in intact and scopolamine-induced amnesic mice. The following results were obtained: 1) Repeated administration of Y-8894 (1, 2.5 and 5 mg/kg, i.p.) significantly increased the number of initial correct responses (ICR) in the training session in intact mice, facilitating the learning of the maze task. Dihydroergotoxine (5 mg/kg, i.p.) significantly facilitated the learning of this task in the initial stage of the training session, but non-specifically inhibited the performance in the late stage of training. Ca-hopantenate did not modify the learning of this task. 2) A single administration of Y-8894 (2.5 or 5 mg/kg, i.p.) showed an antagonistic effect on scopolamine (1 mg/kg, s.c.)-induced amnesic mice. Dihydroergotoxine (5 mg/kg, i.p.) and Ca-hopantenate (500 mg/kg, i.p.) also significantly antagonized the ICR-decreasing effect of scopolamine. These results suggest that Y-8894 has an ameliorative and/or facilitative effect on learning and memory in the radial maze task, and Y-8894 is more potent than dihydroergotoxine and Ca-hopantenate.

Amnesia↗
PubMed2006

[Effect of citicoline on spatial learning and memory of rats after focal cerebral ischemia].

OBJECTIVE: To investigate the effects of citicoline on spatial learning and memory of rats after focal cerebral ischemia. METHODS: The rats were randomly divided into sham-operation group, ischemia control group and citicoline group. In the later two groups, focal cerebral ischemia model was established by introducing an intraluminal filament into the left middle cerebral artery, and citicoline (500 mg/kg) or 0.9% NaCl was administered intraperitoneally once a day for 2 weeks after the operation. The rats in the sham-operation group were not subjected to middle cerebral artery occlusion (MCAO) with intraluminal filament. The spatial learning and memory functions of the rats were evaluated by Morris water maze test 15 days after MCAO for 5 days. RESULTS: The rats in ischemia control group exhibited serious spatial learning and memory deficits in both place navigation test and spatial probe test. In the former test, the mean escape latency of citicoline-treated rats were significantly shorter than that of ischemia control rats (P<0.01), and in the latter test significant diffidence was noted between citicoline and ischemia control groups in the percentage time spent in the former platform quadrant and frequency of crossing the former platform (P<0.05). CONCLUSION: Citicoline can improve the spatial learning and memory function of rats after focal cerebral ischemia.

Animals↗
PubMed2003

Learning and memory deficits in Notch mutant mice.

Notch is a critical component of evolutionarily conserved signaling mechanisms that regulate development and may contribute to plasticity-related processes, including changes in neurite structure and maintenance of neural stem cells. Deficits in the Notch pathway are responsible for Alagille and Cadasil syndromes, which are associated with mental retardation and dementia. Additionally, in postmitotic neurons, Notch proteins interact with presenilins and with beta-amyloid precursor protein and could therefore have a role in the memory deficits associated with familial and sporadic Alzheimer's disease. To test if alterations in Notch signaling can lead to learning and memory deficits, we studied mice with mutations in this pathway. Here, we show that null heterozygous mutations in Notch1 result in deficits in spatial learning and memory without affecting other forms of learning, motor control, or exploratory activity. We also show that null heterozygous mutations in the downstream cofactor RBP-J result in similarly specific spatial learning and memory deficits. These data indicate that a constitutive decrease in Notch signaling can result in specific learning and memory deficits and suggest that abnormalities in Notch-dependent transcription may contribute to the cognitive deficits associated with Alzheimer's disease and Alagille and Cadasil syndromes.

Analysis of Variance↗
PubMed2006

Effect of non-specific HCN1 blocker CsCl on spatial learning and memory in mouse.

It has been suggested that HCN1 is primarily expressed in hippocampus, however little is known about its effects on spatial learning and memory. In the present study, we investigated the effects of non-specific HCN1 blocker CsCl on spatial learning and memory by using Morris water maze and in situ hybridization in mice. The results showed CsCl 160 mg/kg ip for 4 days, and the mean escape latency was 34 s longer than that of normal control (P<0.01). In hippocampal tissues, staining for the HCN1 mRNA was stronger in the DG and CA1 region of the hippocampus (P <0.05, P<0.05, when CsCl-administration group was compared with normal group). Our results suggested that CsCl could significantly affect the spatial learning and memory in mice, and HCN channel is involved in the process of learning and memory.

Animals↗
PubMed2000

Repeated acquisition and performance chamber for mice: a paradigm for assessment of spatial learning and memory.

Molecular genetic manipulation of the mouse offers the possibility of elucidating the function of individual gene products in neural systems underlying learning and memory. Many extant learning paradigms for mice rely on negative reinforcement, involve simple problems that are relatively rapidly acquired and thus preclude time-course assessment, and may impose the need to undertake additional experiments to determine the extent to which noncognitive behaviors influence the measures of learning. To overcome such limitations, a multiple schedule of repeated acquisition and performance was behaviorally engineered to assess learning vs rote performance within-behavioral test session and within-subject utilizing an apparatus modified from the rat (the repeated acquisition and performance chamber; RAPC). The multiple schedule required mice to learn a new sequence of door openings leading to saccharin availability in the learning component during each session, while the sequence of door openings for the performance component remained constant across sessions. The learning and performance components alternated over the course of each test session, with different auditory stimuli signaling which component was currently in effect. To validate this paradigm, learning vs performance was evaluated in two inbred strains of mice: C57BL/6J and 129/SvJ. The hippocampal dependence of this measure was examined in lesioned C57BL/6J mice. Both strains exhibited longer latencies and higher errors in the learning compared to the performance component and evidenced declines in both measures across the trials of each session, consistent with an acquisition phenomenon. These same measures showed little or no evidence of change in the performance component. Whereas three trials per session were utilized with C57BL/65 mice in each component, behavior of 129/SvJ mice could only be sustained for two trials per component per session, demonstrating differences in testing capabilities between these two strains under these experimental conditions and thus precluding the ability to make systematic strain comparisons of learning capabilities. Hippocampal lesions in C57BL/6J mice resulted in substantially longer latencies and increased errors in the learning but not the performance component, demonstrating the importance of this region to spatial learning as measured in the RAPC. In aggregate, this positive reinforcement-based operant paradigm to evaluate murine spatial learning detects strain differences and hippocampal dependence and permits explicit differentiation of the impact of noncognitive contributions to learning measures on a within-subject, within-session basis.

Animals↗
PubMed2006

Posttraumatic stress disorder: memory and learning performance in children and adolescents.

BACKGROUND: Despite the wealth of information in adult posttraumatic stress disorder (PTSD) literature, few studies have explored the memory and learning performance of trauma-exposed youth. This study examined if memory deficits are associated with PTSD or with trauma exposure in the absence of PTSD. METHODS: Youth exposed to traumatic incidents underwent clinical interviews to diagnose PTSD and exclude major comorbid disorders. Youth with conditions that could impede performance on a memory scale (e.g., limited intellectual functioning, current substance abuse, psychopharmacological treatment) were excluded. Three groups of participants were identified (PTSD positives [n = 29], traumatized PTSD negatives [n = 62], and nontraumatized control subjects [n = 40]). Participants completed the Wide Range Assessment of Memory and Learning (WRAML). RESULTS: Youth with PTSD evidenced significantly lower scores on the WRAML General Memory, Verbal Memory, and Learning indices compared with nontraumatized control subjects. With the exception of Verbal Memory, youth with and without PTSD performed comparably on all other indices. Nonsignificant differences were noted on the Visual Memory Index. CONCLUSIONS: General memory and verbal memory impairments as evidenced in adult populations were observed among this sample of youth. Given the developmental trajectory of memory capabilities, the implications of such early trauma exposure and memory deficits are considered.

Adolescent↗
PubMed2006

Protective effects of compound FLZ on beta-amyloid peptide-(25-35)-induced mouse hippocampal injury and learning and memory impairment.

AIM: To study the protective effects of compound FLZ, a novel synthetic analogue of natural squamosamide, on learning and memory impairment and lesions of the hippocampus caused by icv injection of beta-amyloid(25-35)(Abeta(25-35)) in mice. METHODS: Mice were icv injected with the Abeta(25-35) (15 nmol/mouse), and then treated with oral administration of 75 mg/kg or 150 mg/kg of FLZ once daily for 16 consecutive days. The impairment of learning and memory in mice were tested using step-down test and Morris water maze test. The content of malondialdehyde (MDA) and the expressions of acetylcholinesterase (AChE), Bax, and Bcl-2 in the CA1 region of the mouse hippocampus were measured by biochemical and immunohistochemical analysis, respectively. The pathological damages of hippocampus were observed using a microscope. RESULTS: FLZ (75 mg/kg, 150 mg/kg) significantly attenuated Abeta(25-35)-induced impairment of learning and memory in the step-down test and Morris water maze test. FLZ also reduced pathological damages to the hippocampus induced by Abeta(25-35). Furthermore, FLZ prevented the increase of AChE and Bax, and the decrease of Bcl-2 immunoreactive cells in the CA1 region of the hippocampus, and reduced the increase of MDA content in the hippocampus in mice injected with Abeta(25-35). CONCLUSION: FLZ has protective action against the impairment of learning and memory and pathological damage to the hippocampus induced by icv injection of Abeta(25-35) in mice.

Acetylcholinesterase↗
PubMed2004

[Effects of combined stress of high +Gz and noise on learning and memory in rats].

OBJECTIVE: To study the effect of combined stress of noise and + Gz on learning and memory in rats. METHOD: Thirty-two male SD rats were randomly divided into 4 groups: control group, +10 Gz/3 min group, 90 dB(A)/30 min noise group, combined stress group (+10 Gz/3 min and 90 dB(A)/30 min), 8 rats in each group. Changes of learning and memory after stresses were measured by means of Y-maze test, open field test and step-through test. RESULT: As compared with control group and noise group, the number of correct reactions decreased significantly (P<0.01) and the reaction time increased significantly (P<0.01) in combined stress group at all time after stress; time stay in center grille (TSCG) increased significantly immediately after stress (P<0.01). When compared with control group, total time (TT) and number of error (NE) increased significantly (P<0.01) while latent time (LT) decreased significantly immediately and 6 d after stress (P<0.01). As compared with +10 Gz group, number of correct reactions in combined stress group decreased significantly (P<0.05) and reaction time increased significantly (P<0.01) immediately after stress. CONCLUSION: It is suggested that combined stress of noise and +Gz may impair learning and memory of rats, and +Gz seems to contribute more to the combined effects.

Acceleration↗
PubMed2001

Neurosteroids in learning and memory processes.

The discovery that neurosteroids could be synthesized de novo in the brain independent from the periphery and display neuronal actions led to great enthusiasm for the study of their physiological role. Pharmacological studies suggest that neurosteroids may be involved in several physiological processes, such as learning and memory. This chapter summarizes the effects of the administration of neurosteroids on learning and memory capabilities in rodents and in models of amnesia. We address the central mechanisms involved in mediating the modulation of learning and memory processes by neurosteroids. In this regard, the neurosteroid-modulated neurotransmitter systems, such as gamma-aminobutyric acid type A, N-methyl-D-aspartate, and cholinergic and sigma opioid systems, appear to be potential targets for the rapid memory alteration actions of neurosteroids. Moreover, given that some neurosteroids affect neuronal plasticity, this neuronal change could be involved in the long-term modulation of learning and memory processes. To understand the role of endogeneous neurosteroids in learning and memory processes, we present some physiological studies in rodents and humans. However, the latter do not successfully prove a role of endogenous neurosteroids in age-related memory impairments. Finally, we discuss the relative implication of a given neurosteroid vs its metabolites. For this question, a new approach using the quantitative determination of traces of neurosteroids by mass spectrometry seems to have potential for examining the role of each neurosteroid in discrete brain areas in learning and memory alterations, as observed during aging.

Animals↗
PubMed2000

The effects of long-term ovariectomy and estrogen replacement therapy on learning and memory in monkeys (Macaca fascicularis).

This study determined the effects of estrogen loss and replacement therapy on learning and memory function in monkeys (Macaca fascicularis). The ability to learn, remember, and perform reversals of object discriminations and the accuracy on a spatial delayed response task were found to be comparable in young adult surgically menopausal monkeys receiving estrogen or placebo treatment for 5 or 16 months. Learning and memory abilities were comparable with baseline values following 2, 12, or 24 months of ovariectomy in monkeys. Pre- and postoperative injections of scopolamine in a subset of monkeys revealed only subtle increases in sensitivity on the delayed response task following ovariectomy. These observations in surgically menopausal monkeys have some parallels with those made in surgically menopausal women and suggest that, in the absence of other confounding factors, certain aspects of learning and memory may not be influenced by estrogen in primates.

Animals↗
PubMed2000

Des-tyrosine(1) dynorphin A-(2-13) improves carbon monoxide-induced impairment of learning and memory in mice.

The effects of des-tyrosine(1) dynorphin A-(2-13) (dynorphin A-(2-13)) on carbon monoxide (CO)-induced impairment of learning and memory in mice were investigated using a Y-maze task and a passive avoidance test. The lower percentage alternation and shorter step-down latency of the CO-exposed group indicated that learning and/or memory impairment occurred in mice 5 and 7 days after CO exposure, respectively. Administration of dynorphin A-(2-13) (1.5 and/or 5.0 nmol/mouse, intracerebroventricularly (i.c.v.)) 30 min before behavioral tests improved the CO-induced impairment in alternation performance and the CO-induced shortened step-down latency. We previously reported that dynorphin A-(1-13) improved the impairment of learning and/or memory via kappa opioid receptor mediated mechanisms. To determine whether the effect of dynorphin A-(2-13) was also mediated via kappa opioid receptors, we attempted to block its action using a selective kappa opioid receptor antagonist, nor-binaltorphimine (nor-BNI). Nor-BNI (4.9 nmol/mouse, i.c.v.) did not block the effects of dynorphin A-(2-13) on the CO-induced impairment of learning and/or memory. These results indicate that dynorphin A-(2-13) improves impairment of learning and/or memory via a non-opioid mechanism.

Animals↗
PubMed2003

[Effect of shu di-huang on the transmitter and receptor of amino acid in brain and learning and memory of dementia model].

OBJECTIVE: To observe the mechanism of SHU-Dihuang on the function of learning and memory. METHOD: On the dementia model mouse caused by AlCl3 and the rats model damaged thalamic arcuate nucleus with MSG, we observed the function of learning and memory by step down task and Morris water maze task, mensurated the content of glutamic acid and gamma-aminobutyric acid by TLC, and observed the expression of NMDAR1 and GABAR in hippocampi by immunohistochemical means. RESULT: Shu Di Huang could decrease the times of mistakes and prolong the incubation period in step down task, and shorten the incubation period of seeking the platform in Morris water maze task. Shu Di Huang could adjust the content of Glu and GABA in brain, and increase the expression of hippocampal NMDAR1 and GABAR as well. CONCLUSION: Shu Di Huang can improve the function of learning and memory of dementia animal model, and its mechanism may be related to the adjustment of the content of Glu and GABA in brain, and increase of the expression of hippocampal NMDAR1 and GABAR.

Animals↗
PubMed2002

[Role of melatonin in spatial learning and memory in rats and its mechanism].

It has been suggested that melatonin is involved in learning and memory. In the present study, we investigated the effects of melatonin on spatial learning and memory in rats, using Morris water maze and electrophysiological methods. The results are as follows. (1) During a six-day water maze training, the mean escape latency of melatonin group in the last 4 days was 30.02+/-3.6 s, and that of control group was 18.44+/-2.7 s (P<0.01). The crossing annulus coefficient of melatonin group was 25.68+/-2.32%, and that of control group was 43.33+/-2.85% (P<0.01). (2) Microinjection of melatonin into CA1 area inhibited long-term potentiation (LTP). Sixty minutes after tetanus, the field excitory postsynaptic potentials (fEPSP) slope of group C (n=7 0.5 microliter saline) was 169.71+/-6.48 % of the baseline, and that of group M2 (n=6, 2 microgram melatonin) was 114.28+/-1.80% of the baseline. The difference is significant (P<0.01). (3) We also investigated the effects of melatonin on LTP after administration of scopolamine. Sixty minutes after tetanus, the fEPSP slope of group SM (n=6, 2 microgram scopolamine before 2 microgram melatonin) was 113.70+/-5.55% of the baseline. It showed a significant decrease compared with group C (P<0.01). However, there was no difference between groups SM and M2 (P>0.05, i.v.). The results obtained by applying melatonin after bicuculline were different from those after scopolamine. Sixty minutes after tetanus, the fEPSP slope of group BM (n=7, 1 microgram bicuculline before 2 microgram melatonin) was 162.29+/>10.52% of the baseline. Compared with group C, there is no significant difference (P>0.05); but compared with group M2, the difference is significant (P<0.01). Our results showed that application of melatonin in rats significantly inhibited not only spatial learning and memory, but also LTP in CA1 area. Furthermore, the results indicate that the inhibition of LTP by melatonin may not be mediated by cholinergic system, but may be through the modulation of GABAergic system.

Animals↗
PubMed2001

Effects of repeated hydrogen sulphide (H2S) exposure on learning and memory in the adult rat.

The effects of repeated exposure (125 ppm) of hydrogen sulphide (H2S) on learning and memory in the rat were investigated. A 16-arm radial arm maze (RAM) was used to examine neurobehavioural functioning in a series of three experiments. Experiment 1 involved training animals on a complex spatial maze task, prior to a 5-week period of exposure to H2S or a control gas mixture. Rats were tested for maze retention after each 5-day exposure period. It was determined that repeated H2S exposure had no effect on memory for a previously learned spatial task. Experiment 2 was conducted to determine whether H2S interferes with the acquisition of a novel spatial task. Naïve animals received daily maze training and exposure (H2S or control) sessions over an extended 11-week period (48 sessions). The results indicated that the groups were comparable on four of five measures of maze performance. H2S animals were impaired in their ability to find all of the reinforcers prior to the end of a trial, suggesting that H2S had an effect on performance rate, but not acquisition of the maze task. Finally, Experiment 3 was conducted to determine what role proactive interference might play in H2S-related brain impairment. Animals from the preceding experiment were trained on a new reversed contingency maze task. H2S animals made more overall arm entries than controls, suggesting that H2S may impair learning by increasing the animals' susceptibility to interference from irrelevant stimuli. The prefrontal cortex was discussed as a potential target site of H2S. The pathophysiological mechanisms underlying the effect of H2S on normal brain function have yet to be identified.

Administration, Inhalation↗