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PubMed1991

The Drosophila dunce locus: learning and memory genes in the fly.

The dunce gene, one of several genes critical for normal learning and memory in Drosophila, is organized in a complex and bizarre way, with enormous introns containing several other unrelated genes. Recent studies have focused on the spatial expression pattern of the product, cAMP phosphodiesterase, and have provisionally identified the mushroom bodies as important sites of action of dunce within adult brain. In addition, the recent cloning and characterization of dunce counterparts from mammals has revealed that these too may participate in animal behavior and, in particular, in the regulation of mood.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1995

Learning and memory in the honeybee.

Insects are favorable subjects for neuroethological studies. Their nervous systems are relatively small and contain many individually identifiable cells. The CNS is highly compartmentalized with clear separations between multisensory higher order neuropiles in the brain and neuropiles serving sensory-motor routines in the ventral cord (Huber, 1974). The rich behavior of insects includes orientation in space and time, visual, chemical, and mechanical communication, and complex motor routines for flying, walking, swimming, nest building, defense, and attack. Learning and memory, though, are not usually considered to be a strong point of insects. Rather, insect behavior is often regarded as highly stereotyped and under tight control of genetically programmed neural circuits. This view, however, does not do justice to the insect order of Hymenoptera (bees, wasps, ants). Most Hymenopteran species care for their brood either as individual females or as a social group of females. Consequently, they regularly return to their nest site to feed, protect, and nurse the larvae, store food, and hide from adverse environmental conditions. Since they search for food (prey; nectar and pollen on flowers) at unpredictable sites, they have to learn the celestial and terrestrial cues that guide their foraging trips over long distances and allow them to find their nest sites (central place foraging; von Frisch, 1967; Seeley, 1985). They learn to relate the sun's position and sky pattern of polarized light to the time of the day (Lindauer, 1959), and landmarks are learned in relationship to the nest site within the framework of the time-compensated sun compass. The honeybee communicates direction and distance of a feeding place to hive mates by performing a ritualized body movement, the waggle dance (von Frisch, 1967). Associative learning is an essential component of the bee's central place foraging behavior and dance communication. Hive mates attending a dance performance learn the odor emanating from the dancing bee and seek it at the indicated food site. The odor, color, and shape of flowers are learned when the bee experiences these stimuli shortly before it finds food (nectar, pollen). This appetitive learning in bees has many characteristics of associative learning well known from mammalian learning studies (Menzel, 1985, 1990; Bitterman, 1988). It follows the rules of classical and operant conditioning, respectively, so that stimuli or behavioral acts are associated with evaluating stimuli. Since associative learning, especially of the classical type, is well described at the phenomenological and operational level (Rescorla, 1988), it provides a favorable approach in the search for the neural substrate underlying learning and memory.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1992

Effects of lesion of the inferior olivary complex by 3-acetylpyridine on learning and memory in the rat.

DA/HAN-strained male rats (pigmented rats) were submitted to two experimental tasks consisting of spatial learning (water-escape) and a passive avoidance conditioning. Both these tasks were performed by different animals. In order to destroy the inferior olivary complex, the animals were injected with 3-acetylpyridine either 9 days prior to the initial learning session or 24 h after completion of the learning task. They were retested (retrieval test) 10 days after the initial learning was achieved. Learning and retention were compared to those noted in control rats. Administration of 3-acetylpyridine before the initial learning did not prevent the spatial learning but the scores were greatly altered and the number of trials needed to reach the fixed learning criterion was much greater than in controls. However, 10 days later the animals had memorized their initial experience. Injection of 3-acetylpyridine after the initial learning session impaired memory: the animals had completely forgotten their initial learning. It can therefore be concluded that lesion of the afferent climbing fibres to the cerebellar cortex alters learning and retention of a spatial task. Such a lesion does not interfere with learning and retention of a passive avoidance conditioning, since in this condition the experimental animals injected with 3-acetylpyridine either before or after the initial learning behave similarly to controls. The effects of the inferior olivary complex lesion are obviously different according to the task to be learnt, suggesting that these two tasks do not require the integrity of the same nervous structures.

Animals↗

PubMed1991

[Effects of tianeptine on learning and memory in mice. Improvement of impairments induced by chronic alcoholism and brain aging].

Tianeptine, a molecule with antidepressant properties, was found to affect certain learning and memory impairments induced by chronic alcoholism and aging in the mouse. Impairment in spontaneous alternation induced by chronic (12 months) alcohol intake and accelerated loss of spatial learning skills related to aging disappeared totally after administration of tianeptine (10 mg.kg-1). In certain situations (discrimination acquisitions), tianeptine was uneffective in older animals at this dosage, but had a facilitating effect in young animals. The effects of tianeptine on serotonin mediated transmission and the probable implication of hypofunctioning central cholinergic systems in the observed impairments are discussed. Tianeptine might reduce the inhibiting action of serotonin terminaisons on acetylcholine release and might thus permit normal cholinergic transmission.

Aging↗

PubMed1993

The effects of anti-hypertensive medication on learning and memory.

1. The aim of the study was to investigate whether there were differential effects of three different anti-hypertensive medications (cilazapril, atenolol, nifedipine) on cognitive function. 2. A sub-group of patients participating in a large clinical trial of these three drugs, randomly allocated between the three drug conditions, received cognitive assessment at two points before the commencement of treatment and then after 12 and 24 weeks of treatment. Seventy-six patients began treatment, and 55 completed the full course. 3. Tests of learning and memory were designed specially for the study, with a different but comparable version administered on each assessment occasion, in a fixed order. 4. No significant differences between drug groups were found in any index of learning or memory, at any testing occasion. The results were the same whether or not treatment non-completers were included in the analysis.

Adult↗

PubMed2004

Simulated apoptosis/neurogenesis regulates learning and memory capabilities of adaptive neural networks.

Characterization of neuronal death and neurogenesis in the adult brain of birds, humans, and other mammals raises the possibility that neuronal turnover represents a special form of neuroplasticity associated with stress responses, cognition, and the pathophysiology and treatment of psychiatric disorders. Multilayer neural network models capable of learning alphabetic character representations via incremental synaptic connection strength changes were used to assess additional learning and memory effects incurred by simulation of coordinated apoptotic and neurogenic events in the middle layer. Using a consistent incremental learning capability across all neurons and experimental conditions, increasing the number of middle layer neurons undergoing turnover increased network learning capacity for new information, and increased forgetting of old information. Simulations also showed that specific patterns of neural turnover based on individual neuronal connection characteristics, or the temporal-spatial pattern of neurons chosen for turnover during new learning impacts new learning performance. These simulations predict that apoptotic and neurogenic events could act together to produce specific learning and memory effects beyond those provided by ongoing mechanisms of connection plasticity in neuronal populations. Regulation of rates as well as patterns of neuronal turnover may serve an important function in tuning the informatic properties of plastic networks according to novel informational demands. Analogous regulation in the hippocampus may provide for adaptive cognitive and emotional responses to novel and stressful contexts, or operate suboptimally as a basis for psychiatric disorders. The implications of these elementary simulations for future biological and neural modeling research on apoptosis and neurogenesis are discussed.

Animals↗

PubMed2004

Effect of kami-untan-to on the impairment of learning and memory induced by thiamine-deficient feeding in mice.

We have recently reported that thiamine deficient (TD) mice show an impairment of learning and memory on the 20th day after start of TD feeding. Interestingly, it has been reported that the kampo medicine, "kami-untan-to" (KUT) may be useful as a potential therapeutic agent in diseases associated with cholinergic deficit such as Alzheimer's disease. In the present study, we investigated the effects of KUT on the impairment of memory-related behavior concomitant with psychoneuronal symptoms after TD feeding in mice. Oral administration of KUT had no effect on the food intake, body weight or locomotor activity in TD mice, but the mortality rate in the KUT-treated TD group was significantly lower compared with that in the non-treated TD group. Daily administration of KUT from the 1st day of TD feeding protected against the impairment of memory-related behavior induced by TD. The intensity of the choline acetyltransferase fluorescence decreased in the field of CA1 and dentate gyrus in the hippocampus in TD mice compared with pair-fed mice as the control group, and KUT treatment inhibited this decrease. These results suggest that the effect of KUT on the impairment of memory-related behavior induced by TD feeding may be closely related to the activation of cholinergic neurons in the hippocampus.

Animals↗

PubMed1994

Defects of immune cells in the senescence-accelerated mouse: a model for learning and memory deficits in the aged.

We investigated immune characteristics of SAMP8 mice that have early learning and memory deficiencies and a short life span accompanied by normal growth and compared them to those of SAMR1 mice that have a normal aging process. The indexes of immune responsiveness used were natural killer (NK) cell activity, in vitro anti-SRBC (sheep red blood cells) antibody responses, cell proliferation, and interleukin 2 (IL-2)-producing activity in response to concanavalin A of spleen cells. As early as 2 months after birth, SAMP8 mice showed markedly low activity for all the indexes that was not due to a delay of their development. Endogenous NK cell activity in SAMP8 mice remained low or at the background level for a few months, but the trace level of this activity increased after treatment with an immune potentiator of polyinosinic-polycytidylic acid. Because the number of cells bearing an NK cell marker in SAMP8 mice was comparable to that for SAMR1 mice, the low NK cell activity found for SAMP8 mice may not be caused by a low number of precursor cells but by defects in the lytic mechanism or low competence. Flow cytometry analyses showed that the size of the lymphocyte fraction in the spleen is the same for both strains and that T cell fractions, especially of CD4+ T cells in SAMP8 mice are smaller than in SAMR1 mice. In contrast, a B cell fraction was somewhat larger in SAMP8 mice. Together with the fact that the spleen cells of both strains equally stimulated allogeneic T cells in the mixed lymphocyte reaction, the low helper T cell activity in antibody responses, even under the condition of cell-number equivalence, indicates a qualitative defect of CD4+ T cells in SAMP8 mice. This defect probably is closely related to the low endogenous activity of NK cells.

Aging↗

PubMed1995

A mouse homolog of dunce, a gene important for learning and memory in Drosophila, is preferentially expressed in olfactory receptor neurons.

The dunce (dnc) gene in Drosophila codes for a cyclic adenosine monophosphate-specific phosphodiesterase (PDE). Flies with a mutation at this locus exhibit severe deficits in learning and memory. We have begun to analyze the neural distribution of mammalian homologs of dnc in the mouse. Surprisingly, in situ hybridization and northern blotting using a probe specific for one of the four mammalian dnc homologs (mPDE2) reveals high levels of expression in the olfactory neuroepithelium. Anti-mPDE2 antibody confirms that this PDE protein is abundant in the axons and dendrites of the olfactory receptor neurons but is conspicuously absent from the cilia, where the initial events in olfactory signal transduction occur. Lower levels of mPDE2 were also detected throughout the brain and in the testis. These findings suggest an important modulatory role for mPDE2 in mammalian olfaction.

Animals↗

PubMed2002

A new area in the human brain associated with learning and memory: immunohistochemical and functional MRI analysis.

Previous studies identified a new brain area, the marginal division (MrD), at the caudomedial border of the neostriatum in the brain of the rat, cat and monkey. The MrD was distinguishable from the rest of the striatum by the presence of spindle-shaped neurons, specific connections, and dense immunoreactivity for neuropeptides and monoamines in fibers, terminals and neuronal somata. Behavioral testing demonstrated that the MrD contributes to learning and memory in the rat. In the present study, the structure and the function of the MrD were investigated in the human brain. The presence of spindle-shaped neurons and the distribution of neurotransmitters in the MrD were evaluated by immunocytochemical methods. The function of the MrD was identified with functional magnetic resonance imaging (fMRI) of healthy volunteers tested with an auditory digital working memory task. Highly active areas were observed in the prefrontal cortex and MrD with left sided predominance during performance of the task, but other parts of the neostriatum were not excited and the MrD was not activated in a control test of non-working memory. The results of the present investigation therefore indicate the existence of a new area associated with learning and memory function in the human brain. The MrD probably plays an important role in the execution of digital working memory and appears to link the limbic system and the basal nucleus of Meynert. The MrD may also be involved in the mechanism of Alzheimer's disease.

Adult↗

PubMed1996

Verbal learning and memory: does the modal model still work?

This chapter focuses on recent research concerning verbal learning and memory. A prominent guiding framework for research on this topic over the past three decades has been the modal model of memory, which postulates distinct sensory, primary, and secondary memory stores. Although this model continues to be popular, it has fostered much debate concerning its validity and specifically the need for its three separate memory stores. The chapter reviews research supporting and research contradicting the modal model, as well as alternative modern frameworks. Extensions of the modal model are discussed, including the search of associative memory model, the perturbation model, precategorical acoustic store, and permastore. Alternative approaches are discussed including working memory, conceptual short-term memory, long-term working memory, short-term activation and attention, processing streams, the feature model, distinctiveness, and procedural reinstatement.

Journal Article↗

PubMed2006

Differential effects of haloperidol, clozapine and olanzapine on learning and memory functions in mice.

Many schizophrenic patients exhibit impairments in neurocognitive functions. Typical antipsychotic drugs such as haloperidol, have limited or even detrimental influence on cognitive functions. In contrast, atypical antipsychotic drugs, such as clozapine and olanzapine, may improve memory function in schizophrenics. However, only a few studies have been conducted to directly compare the effects of olanzapine, clozapine and haloperidol on memory functions in animal models. Thus, their effects on this issue were investigated in the present studies by using one-way step-through passive avoidance task and Morris water maze as models of learning and memory. The results showed that olanzapine did not affect acquisition, consolidation or retrieval process in step-through test. Moreover, it improved spatial learning function in mice in Morris water maze task. Clozapine and haloperidol appeared to impair acquisition process and consolidation process, respectively, in step-through test. Both drugs impaired spatial learning function in mice in Morris water maze task. The results suggested a positive implication for the clinical medication of olanzapine in schizophrenic treatment.

Animals↗

PubMed1987

Enhancement of performance by methyl beta-carboline-3-carboxylate, in learning and memory tasks.

Benzodiazepines are known to induce a profound anterograde amnesia in man. In this report, it is shown that methyl beta-carboline-3-carboxylate (beta-CCM), an inverse agonist of the benzodiazepine receptor, has the opposite effect; it enhances performance in learning and memory tasks. Three different learning models were used: habituation to a new environment and passive avoidance in mice and imprinting in chicks. The opposite effects of both beta-CCM and the benzodiazepine diazepam were blocked by administration of the benzodiazepine receptor antagonist Ro 15-1788, providing evidence that the benzodiazepine receptor is involved in these effects.

Animals↗

PubMed1993

Analysis of verbal memory and learning by means of selective reminding procedure in Alzheimer and multi-infarct dementias.

Several studies aimed at defining the characteristics of memory impairment resulting from different etiologic forms of dementia have been inconclusive. These unsatisfactory results might be due to the enrollment of various groups of demented patients not matched for disease severity, as well as the use of different psychometric procedures. The object of the present study was to verify the existence of a different pattern of verbal memory impairment that might be useful in clinical practice in two groups of AD and MID patients who were matched for degree of cognitive deterioration. Thirty-seven AD and 41 MID patients were assessed for memory and learning by means of the Supraspan Verbal Learning test (Selective Reminding by Buschke-Fuld), which provides a simultaneous analysis of storage, retention and retrieval abilities. Twenty-four normal subjects were studied as a control group. No differences in storage and retrieval mean scores were found between the two groups. AD patients showed a higher mean score in random retrieval; the mean score in selective retrieval at the end of learning was significantly higher in MID patients, suggesting a more impaired retrieval from long-term storage in AD than in MID patients. Intrusions, defined as inappropriate recurrences from preceding tests, were observed more frequently in AD patients. The presence of intrusions and the delayed retrieval score showed a good level of sensitivity and specificity in the differential diagnosis between the two groups.

Aged↗

PubMed2006

Cyclin-dependent kinase 5 in synaptic plasticity, learning and memory.

Cyclin-dependent kinase 5 (Cdk5) is a serine/threonine kinase with a multitude of functions. Although Cdk5 is widely expressed, it has been studied most extensively in neurons. Since its initial characterization, the fundamental contribution of Cdk5 to an impressive range of neuronal processes has become clear. These phenomena include neural development, dopaminergic function and neurodegeneration. Data from different fields have recently converged to provide evidence for the participation of Cdk5 in synaptic plasticity, learning and memory. In this review, we consider recent data implicating Cdk5 in molecular and cellular mechanisms underlying synaptic plasticity. We relate these findings to its emerging role in learning and memory. Particular attention is paid to the activation of Cdk5 by p25, which enhances hippocampal synaptic plasticity and memory, and suggests formation of p25 as a physiological process regulating synaptic plasticity and memory.

Animals↗

PubMed2000

Learning and memory in mice treated with choline oxidase, a hydrolytic enzyme for choline.

Learning and maintenance of memory in mice intraperitoneally (IP) injected with choline oxidase (ChO, 6 units/g), a hydrolytic enzyme for choline (Ch), were assessed by means of a step-through passive-avoidance task. The ChO treatment induced a hydrolysis of free Ch in plasma, which in turn, induced a decrease in cerebral acetylcholine (ACh) release. In the learning test, the ChO-treated mice showed significant inhibition to learn the avoidance from electric shock. In the retention test, the impairment of the memory once established was not produced by posttreated ChO. We concluded that the decreased cerebral cholinergic neurotransmission induced by ChO retarded acquisition of passive-avoidance learning more readily than the maintenance of memory.

Alcohol Oxidoreductases↗

PubMed1986

Effects of meclofenoxate and Extr. Rhodiolae roseae L. on electroconvulsive shock-impaired learning and memory in rats.

In experiments on albino rats, the authors studied the effects of meclofenoxate and Extr. Rhodiolae roseae on the memory-impairing action of convulsant electroshock. "Step-down" passive avoidance training with negative reinforcement was used to trace the changes in memory. Meclofenoxate administered i.p. in a dose of 100 mg/kg body weight for five days prevented the retrograde amnesia observed after convulsant electroshock upon retention testing on the 3rd and 24th hr after the end of the training session. The Rhodiola extract administered orally in a dose of 0.10 ml/rat for 10 days, which in other experimental approaches improved learning and memory, remained ineffective here. The role of biogenic monoamines in the learning- and memory-improving effects of meclofenoxate is considered on the basis of earlier studies by the authors.

Animals↗

PubMed1990

Memory and learning in outpatients with quiescent multiple sclerosis.

In 22 (56%) of 39 quiet-stage multiple sclerosis (MS) patients with at least average intelligence quotients, performances in memory and learning tasks were normal, as compared with those of a control group (24 healthy volunteers). Of the remaining 44% (n = 17), 2 patients were amnesic and 5 had been judged to have suffered cognitive decline. Auditory word learning was particularly vulnerable; however, acquisition rate was not significantly different between MS patients and controls.

Adolescent↗