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PubMed2002

The acid-activated ion channel ASIC contributes to synaptic plasticity, learning, and memory.

Many central neurons possess large acid-activated currents, yet their molecular identity is unknown. We found that eliminating the acid sensing ion channel (ASIC) abolished H(+)-gated currents in hippocampal neurons. Neuronal H(+)-gated currents and transient acidification are proposed to play a role in synaptic transmission. Investigating this possibility, we found ASIC in hippocampus, in synaptosomes, and in dendrites localized at synapses. Moreover, loss of ASIC impaired hippocampal long-term potentiation. ASIC null mice had reduced excitatory postsynaptic potentials and NMDA receptor activation during high-frequency stimulation. Consistent with these findings, null mice displayed defective spatial learning and eyeblink conditioning. These results identify ASIC as a key component of acid-activated currents and implicate these currents in processes underlying synaptic plasticity, learning, and memory.

Acid Sensing Ion Channels↗
PubMed2005

[Disorders in learning and memory processes in the monkey model of Alzheimer's disease: the role of the cerebral cortex associative areas].

Processes of novelty learning and keeping the results in Alzheimer's disease in two groups of rhesus-monkeys (three monkeys in each group), were studied: following neurotoxins administrati- on (I group) and saline administration (II group). In two months after the injections (the C1 stage), considerable differences between the groups were revealed in the task of differentiation among contour shapes. For the I group monkeys the learning was difficult: the correct decision making did not reach 85 %, and the probability of refusing to make a decision increased. For the II group monkeys the learning characteristics were not disturbed. In six months after the injections (the C3 stage) the differences between the groups in the task of differentiation among new stimuli (heads of two monkeys) remained at the same level. When studying characteristics of the operative memory associated with keeping the learning results achieved at the C1 stage, a considerable worsening of these characteristics was revealed: diminishing of the correct decision making probability at the C1 stage (actually to the level of 0.5), increase in the probability of refusing to make a decision. The structural-functional organization of interaction between sensory and cognitive processes in learning and keeping the information in the operative memory, is discussed in association with the control of motivation and attention system and the role of the cortex associative areas.

Alzheimer Disease↗
PubMed1995

Olfactory learning and memory in the honeybee: comparison of different classical conditioning procedures of the proboscis extension response.

Olfactory learning in the honeybee was investigated using the conditioned proboscis extension reflex on restrained individuals. We compared, under the same experimental conditions, the most commonly used conditioning procedures, i.e. 1 trial, 3 massed trials (1 min inter-trial intervals), and 3 spaced trials (10 min inter-trial intervals) procedures, using linalool as the conditioned stimulus. Two experiments were performed in which worker bees were subjected to: (1) a single test at different times (30 s to 14 days) after the conditioning procedure; (2) a first test within 3 h after the conditioning procedure, and were then retested daily (up to 5 tests). The memory trace of a learnt odorant stimulus could last for the lifetime of the bee, even after a single association with sugar. Repeated tests with 1 day inter-test duration induced a strong decrease of the response level, this effect being more pronounced after a 1-trial conditioning.

Animals↗
PubMed1997

Relationship of IQ to verbal learning and memory: test and retest.

The relationship between Wechsler Adult Intelligence Scale-Revised (WAIS-R) IQ and performance on measures of memory was examined in 64 adults tested twice at a 2-week interval. Repeated measures analyses of variance revealed that individuals with Low-Average WAIS-R Full Scale IQ scores performed significantly more poorly than did individuals with Average and High-Average Full Scale IQs on memory measures including the Wechsler Memory Scale-Revised (WMS-R) General Memory and Delayed Recall indices, as well as California Verbal Learning Test (CVLT) Total Words. Learning Slope, and Discriminability. Although all three groups demonstrated significant practice effects on each memory measure, group differences in performance persisted at retest. Multiple regression analyses revealed that WAIS-R factor scores Verbal Comprehension and Freedom from Distractibility accounted for up to 42% of the variance in WMS-R and CVLT indices. Moreover, WAIS-R performance at initial testing accounted for 22-41% of the variance in memory performance at retest. These results are discussed in the context of the construct stabilities of intelligence and memory, as well as the psychometric precision of the tests used to measure these constructs.

Adult↗
PubMed1998

Facilitatory effects of chronically administered citicoline on learning and memory processes in the dog.

1. Citicoline (cytidine (5') diphosphocholine) has been shown to reverse aging-induced memory deficits, scopolamine-induced amnesia and nucleus basalis magnocellularis lesion-induced learning impairment. 2. This study aimed to evaluate the effects of citicoline on learning and retrieval processes in a complex differential reinforcement of response duration schedule in normal dogs. 3. The effects of citicoline on a stabilized performance were also measured in order to be able to differentiate specific memory effects from non specific influences on the motor, neuro-vegetative and motivational systems. 4. The results demonstrate that citicoline can exert facilitatory effects on learning and memory but also on retrieval processes. The complete absence of effects on the stabilized performance and on the motor, neuro-vegetative and motivational systems constitutes arguments in favour of a selectivity of action on the memory processes.

Acoustic Stimulation↗
PubMed1984

[Mechanisms of enkephalin action on learning and memory processes].

The influence of enkephalin on the processes of elaboration and preservation of the defensive conditioned reflexes of bilateral avoidance (CRBA) and conditioned reflexes of passive avoidance (CRPA) in intact rats and animals with changed functional state of serotoninergic system of the brain has been examined. Injection of enkephalin in dose of 10 mkg to intact animals accelerated the elaboration of CRBA not influencing in this case their preservation, but deeply disturbed the CRPA preservation. The excess of serotonin in the brain created by means of 5-oxytryptophan fully prevented the acceleration of CRBA elaboration by enkephalin under the usual conditions. Injection of enkephalin at the background of serotonin lowering and raising in the brain favoured CRBA preservation. Under the enkephalin influence the inclusion of [3H]tyrosine and [14C]lisine in water-soluble and water-insoluble proteins of different cerebral structures lowered. The obtained data testify to participation of serotoninergic system and brain proteins in the mechanisms of enkephalin action to the processes of learning and memory.

5-Hydroxytryptophan↗
PubMed1997

Multiple kainic acid seizures in the immature and adult brain: ictal manifestations and long-term effects on learning and memory.

PURPOSE: While there is increasing evidence that the adverse effects of prolonged seizures are less pronounced in the immature than in the mature brain, there have been few investigations of the long-term effects of recurrent seizures during development. This study examined the effects of multiple administrations of the convulsant kainic acid (KA) on seizure characteristics and spatial learning as a function of brain development. METHODS: To determine the long-term effects of serial KA seizures during ontogeny, saline or convulsant doses of KA were given intraperitoneally 4 times, at 2-day intervals. Immature rats were given KA on P20, P22, P24 and P26; adult rats got KA on P60, P62, P64 and P66. Ictal characteristics and EEGs were recorded. To examine the effects of multiple KA seizures on the retention of spatial learning, water maze testing was performed before (immature group: from P16-19, adult group: from P56-P59) and after (immature: from P60-P63, adult: from P100-P103) KA injections. Finally, histology was performed to compare KA-induced damage at each age. RESULTS: In immature animals, serial KA administration resulted in seizures with a progressively longer onset latency and decreased severity. In contrast, KA serially administered to adult rats caused severe seizures after each of the 4 injections. In immature rats, epileptiform EEG changes were most prominent after the first KA injection, whereas in adults, prolonged paroxysmal EEG patterns were seen after all 4 KA injections. Before KA, both rat pups and adults acquired place learning in the water maze. One month after the final KA injection, there was no deficit in spatial learning retention in the immature group, whereas the adult group had profound impairment compared to age-matched, saline-injected controls. Histology revealed no lesions in immature rats treated multiple times with KA but profound cell loss in hippocampal fields CA4, CA3 and CA1 in rats treated serially with KA as adults. CONCLUSIONS: Previous studies have shown that a single KA injection causes prolonged status epilepticus (which persists for several hours), leading to severe histologic and behavioral sequelae in adult rats but not in pups. Our study extends those findings, demonstrating that immature rats are spared the cognitive and pathological sequelae of multiple injections of convulsant doses of KA as well.

Animals↗
PubMed2002

Hippocampal brain amines in methotrexate-induced learning and memory deficit.

Intrathecal methotrexate in children with leukemia is known to cause seizures, dementia, leukoencephalopathy, and cognitive dysfunction after long-term treatment. To investigate the cognitive dysfunction, male Wistar rats were given multiple intracerebroventricular injections of methotrexate. Its effect on behaviour was tested in the two-compartment conditioned avoidance task and dark-bright arena test. Levels of brain amines in the hippocampal region of the brain were estimated by HPLC. The qualitative and quantitative histopathological changes in the different regions of the hippocampus were studied by cresyl violet staining. Multiple injections (1 or 2 mg/kg) produced convulsions and learning and memory impairment but did not induce anxiolytic activity. They also reduced concentrations of all three brain amines (norepinephrine, dopamine, and serotonin) and the serotonin metabolite 5-hydroxyindoleacetic acid. The CA4 region of the hippocampus was severely affected by intraventricular methotrexate. Disruption of brain monoamines has been proposed as a cause of brain dysfunction from this chemotherapy, and that disruption may in turn involve cytotoxic effects of methotrexate on brain tissue. The outcomes of this study may have therapeutic implications in the management of cancer conditions, particularly in childhood lymphoblastic leukemia.

Animals↗
PubMed2006

Motor functions but not learning and memory are impaired upon repeated exposure to sub-lethal doses of methyl parathion.

Our previous work showed that repeated exposure to methyl parathion (MP) caused a prolonged inhibition of acetylcholinesterase (AChE) activity (approximately 80%) and down-regulation of M(1) and M(2) muscarinic receptors (up to 38%) in rats at brain regions, including frontal cortex, striatum, hippocampus and thalamus. In the present neurobehavioral study, we found this repeated MP treatment had suppressant effects on rat's locomotor activity. However, we observed no evidence of long-term effects of MP on associative learning and memory. Our data demonstrated that repeated exposure to MP caused some functional deficits in CNS, but motor activity and associative learning/memory process might differ in the sensitivity to its toxic effect. The motor dysfunctions in MP-treated rats may be mediated via reciprocal balance between cholinergic and dopaminergic systems at striatum following cholinergic over-stimulation. Our findings also suggest that the CNS deficits induced by repeated exposure to MP or other organophosphate (OP) pesticides cannot be attributed entirely to the inhibition of AChE. To accurately assess the neuro-toxic risk by occupational exposure to sub-lethal doses of MP, novel biomarkers besides in vivo anticholinesterase potency are needed.

Analysis of Variance↗
PubMed2000

The effect of early experience on learning and memory in cuttlefish.

The effect of early experience on the growth and ontogeny of memory in cuttlefish (Sepia officinalis) was studied using an associative learning protocol. Five groups of cuttlefish were reared in different conditions (standard conditions, SC; impoverished conditions, IC; enriched conditions, EC; impoverished then enriched conditions, I/EC; enriched then impoverished conditions, E/IC) from birth to the 3rd month of postembryonic life. Acquisition and retention of the learning task were assessed at 1 and 3 months. Growth was slower and maturation of memory abilities occurred later in cuttlefish from Group IC than in cuttlefish from Group EC, with the maturation rate of memory in cuttlefish from Group SC intermediate between these two groups. Retention performances of cuttlefish from Groups I/EC and E/IC indicated that the environment of rearing during the 2nd and/or 3rd months of life was crucial for the development of memory.

Age Factors↗
PubMed2002

Learning and memory of cue-reward association meaning by modifications of synaptic efficacy in dentate gyrus and piriform cortex.

This article begins with a review of recent experiments investigating the synaptic efficacy changes occurring in rat dentate gyrus and piriform cortex during an associative olfactory task. In all these experiments, animals were trained to discriminate among an artificial cue, a patterned electrical stimulation distributed to the lateral olfactory tract associated with a water reward, and a natural odor associated with a flash of light. Monosynaptic field potential responses evoked by single electrical stimuli to the lateral olfactory tract were recorded in the ipsilateral piriform cortex before and just after each training session. Monosynaptic field and polysynaptic field potentials evoked by single electrical stimuli applied respectively to the lateral perforant pathway and lateral olfactory tract were also recorded in ipsilateral dentate gyrus. The results showed an increase in synaptic efficacy subsequent to the first training session in the dentate gyrus network when compared with piriform cortex at the later stage of the learning. The early increase of monosynaptic response in the dentate gyrus was observed immediately after the first learning session but disappeared 24 h later. Inversely, a synaptic depression developed across sessions, becoming significant at the onset of the last (fifth) session. The polysynaptic potential recorded in this structure increased substantially when rats began to discriminate the leaming cues, usually after the second or third learning session. Then, from the third to the fifth session, an LTP like-phenomenon appeared in piriform cortex when rats perfectly mastered the associations. Experiments using high-frequency stimulation to prevent changes in gyrus dentatus indicated that the onset of the observed depression was necessary for the learning of the olfactory associations. The fact that hippocampal and cortical neuronal networks exhibited different timing in synaptic efficacy changes could physiologically explain learning and memory processes.

Animals↗
PubMed1997

A rotating holeboard procedure for testing drug effects on spatial learning and memory in mice.

A procedure is described herein for evaluating drug effects on acquisition and retention of a spatial learning task in mice. The rotating holeboard apparatus is a rectangular open field containing four open holes arranged in either a four-corner or a row configuration. A mouse is trained to poke its head into a hole and retrieve a food reward from a 'baited' hole which contains a reward on every trial. A massed trials protocol is used where mice are required to learn a reference (trial-independent) memory task in a single session. A retention test is administered 24 h after acquisition. Prominent distal cues are present in the testing room and reliance on proximal visual, olfactory, or tactile cues for locating the baited hole is precluded by rotating the maze on each trial.

Animals↗
PubMed1998

Contextual cueing: implicit learning and memory of visual context guides spatial attention.

Global context plays an important, but poorly understood, role in visual tasks. This study demonstrates that a robust memory for visual context exists to guide spatial attention. Global context was operationalized as the spatial layout of objects in visual search displays. Half of the configurations were repeated across blocks throughout the entire session, and targets appeared within consistent locations in these arrays. Targets appearing in learned configurations were detected more quickly. This newly discovered form of search facilitation is termed contextual cueing. Contextual cueing is driven by incidentally learned associations between spatial configurations (context) and target locations. This benefit was obtained despite chance performance for recognizing the configurations, suggesting that the memory for context was implicit. The results show how implicit learning and memory of visual context can guide spatial attention towards task-relevant aspects of a scene.

Attention↗
PubMed2006

[A study on expression of HIF-1alpha and EPO in the hippocampus of rats with vascular dementia].

OBJECTIVE: To observe the expression rule of hypoxia inducible factor-1 (HIF-1alpha) and erythropoietion (EPO) in the formation of vascular dementia (VD) and investigate the possible pathogenesis of VD. METHODS: Rats of experimental group were treated with a permanent bilateral common carotid arteries (CCA) occlusion (2-VO) for establishing vascular dementia model. Rats were evaluated on learning-memory ability by Y-type water maze test. The dynamic expression of HIF-1alpha and EPO in hippocampal CA1 region were measured by immunohistochemical assay method. RESULTS: (1) The learning-memory ability of rats in VD groups was progressively decreased as the ischemic duration prolonged (P < 0.05); (2) In VD group, the expression of HIF-1alpha and EPO in hippocampal CA1 region were most obvious at 1 w, and then declined progressively but still above the normal level (P < 0.01); (3) In VD group, the expression of HIF-1alpha and EPO at each ischemic point and their corresponding learning-memory ability were in significant correlation at the 0.01 level. CONCLUSION: Both HIF-1alpha and EPO contribute to the formation of VD, and HIF-1/EPO anoxic signal transduction may play a protecting role in this process.

Animals↗
PubMed1990

Learning and memory is reflected in the responses of reinforcement-related neurons in the primate basal forebrain.

Certain basal forebrain neurons encode the learned reinforcement value of objects: they respond differentially to visual stimuli that signal availability of fruit juice (positively reinforcing) or saline (negatively reinforcing) obtained by lick responses in visual discrimination tasks. In this report we describe the rapid, learning-related changes in the responses of these neurons during the acquisition and reversal of the reinforcement contingency of a visual discrimination reversal task. The same neurons also responded differentially to novel and familiar stimuli in 2 recognition memory tasks, in which monkeys applied the learned rule that lick responses to novel stimuli elicited saline and responses to familiar stimuli elicited juice. These differential responses to novel and familiar stimuli thus reflected the reinforcement value of the stimuli. A single presentation of a novel or a familiar stimulus was sufficient to elicit a differential response which was maintained even when the stimulus had not been seen recently. The maintenance of the differential response indicates that these neurons are influenced by a durable memory for the stimuli, estimated to be 30 trials on average. These differential neurons were recorded in the substantia innominata, the diagonal band of Broca, and a periventricular region of the basal forebrain. The responses of the reinforcement-related neurons in these 3 regions were similar in most respects. These results support the conclusion that basal forebrain neurons respond to sensory stimuli that, through learning of different contingencies, signal the availability of reinforcement. We suggest that the properties of learning and memory reflected in these neuronal responses are due to afferent pathways from ventromedial regions of the prefrontal and temporal cortices and the amygdala, and that the responses of these neurons provide an enabling mechanism that facilitates the operation of diverse cortical regions in which specific sensory, motor, or mnemonic functions take place.

Animals↗