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PubMed1985

Cellular mechanisms of learning, memory, and information storage.

In Table 1, we summarize what is convincingly demonstrated to date for the major vertebrate and invertebrate model systems attempting to elucidate cellular mechanisms of associative learning. Two major concerns are the adequacy of the behavioral demonstrations and the completeness and extent of the accompanying neurophysiology. In addressing the issue of behavior, it is important to define clearly which criteria are both necessary and sufficient to infer the involvement of an associative-learning process. Similarly, it is also important to distinguish among those primary characteristics of associative learning in general, and those secondary or tertiary features that serve to define various subclasses. In our view, it would be unreasonable to require that any given preparation exhibit all the defining features of classical conditioning, for example, in order to qualify as a "legitimate" instance of associative learning. This is especially true if the goal is to understand the more general, rather than the specific, mechanisms involved in associative learning. Hence, we emphasize the following as primary features of learned behavior: pairing specificity, stimulus specificity, long-term retention (arbitrarily defined as lasting for at least 24 hr), a moderate degree of reversibility by subsequent experience (e.g. extinction), and demonstrations that nonassociative-learning processes cannot account for features a-c. Where appropriate, we also identified other interesting features of the learned behavior. It is apparent from the table that a major unresolved issue for most of the preparations is the extent to which the behavioral changes are exclusively associative. This is no less true for the vertebrate preparations than it is for the invertebrates. The clearest example of an exclusively associative behavioral change is the rabbit NMR. The learning-produced changes in the invertebrate preparations were all shown, to varying degrees, to be pairing specific. Yet a major unresolved issue is the degree to which apparent examples of associative-learning reflect complex interactions among basically nonassociative-learning processes. The core issue is really quite simple: Does the associative training procedure result in the acquisition of new or qualitatively different behavior; and is there a strict requirement for an associative relation? In addressing the adequacy of the neurophysiological analyses, the major issue is that of localization. Logically, there are two components to this.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Effect of amino acid supplementation to a low-protein diet on brain neurotransmitters and memory-learning ability of rats.

The supplementation of methionine and threonine to a 10% soy protein isolate diet caused sharp decreases in the concentrations of brain tryptophan, serotonin and 5HIAA (5-hydroxyindole acetic acid) (e.g., in the hypothalamus, hippocampus, amygdala, locus coeruleus and brain stem). The serum tryptophan ratio (i.e., the ratio of the serum concentration of tryptophan to the sum of the concentrations of other large neutral amino acids, such as tyrosine, phenylalanine, leucine, isoleucine, valine and methionine) significantly decreased. The changes in catecholamines were small on the supplementation of amino acids to the soy protein diet. In the brightness-discrimination learning test, the number of total responses (R+, correct; R-, incorrect) of rats fed the amino acid-supplemented diet increased as compared with that of rats fed the nonsupplemented diet. The correct response ratio in the primary learning test did not change, but in the reverse learning test, the response ratio of rats fed the amino acid-supplemented diet increased. Therefore, it may be considered that the learning ability is correlated with the nutritional state.

Amino Acids↗
PubMed2005

Evaluation of general behavior, memory, learning performance, and brain sexual differentiation in F1 offspring males of rats treated with flutamide during late gestation.

Flutamide is a drug with antiandrogen effects that are mediated through androgen receptors (ARs). In this study, flutamide was subcutaneously administered to female rats (3, 10 or 30 mg/kg/day) on gestation Days 16-21 to evaluate effects on memory and learning performance in F1 offspring. Brain sexual differentiation was also evaluated by measuring the volume of the sexual dimorphic nucleus of the preoptic area (SDN-POA) and analyzing levels of androgen receptor (AR) mRNA expression in the prostate, hypothalamus and hippocampus. In F1 offspring exposed in utero to flutamide, evaluation of motor activity, learning performance and spatial perception showed that flutamide tended to exert a dose-dependent increase on the motor activity in F1 males, but no significant differences were identified in the other measurements. Prominent changes in development of the SDN-POA were apparent in males after maturation. Doses of > or =3 mg/kg/day resulted in significantly decreased length and volume of the SDN-POA compared to controls. These differences tended to become more marked at higher doses. Volumes of the SDN-POA did not differ significantly between F1 males and females exposed to flutamide at 30 mg/kg/day. AR mRNA was assayed using the dot-blotting method in F1 animals. In flutamide dose groups, AR mRNA expression tended to be increased in the prostate gland and decreased in the hippocampus. These results might suggest that exposure to flutamide in utero might affect controlling AR expression on a hormonal signal transduction system mediated by testosterone. However, these changes were not clearly correlated to learning performance in male offspring other than motor activity.

Androgen Antagonists↗
PubMed1975

Disruption of state-dependent learning (memory retrieval) by emotionally-important stimuli.

State-Dependent Learning (SDL) occurs when a response learned in a particular drug stste does not transfer to another drug state. SDL was demonstrated and disrupted in a modified T-maxe escape learning task, using male hooded rats. SDL groups were trained each day in one drug state (either Librium, 40 mg/kg or sterile water) and then given non-shock test trials in both drug states. SDL Ss showed drug-dependent retention since they turned randomly in opposite-state test trials and significantly above random level (P greather than 0.02) when in the training drug state. For the Transfer Ss, 1k Hz tone was simultaneously paired with foot shock in training and continued to be sounded on every non-shock test trial. Transfer Ss turned in the training direction regardless of drug state. Drug-dependence in the SDL groups and transfer in the Transfer groups were also demonstrated in response latencies. The tones were emotional memory prompters initiating some process that mediated transfer between drug states. The theoretical importance of these results were discussed in relation to energizing and directing functions of emotions and symmetrical and asymmetrical transfer.

Acoustic Stimulation↗
PubMed1998

Effects of aluminum potassium sulfate on learning, memory, and cholinergic system in mice.

AIM: To study the relationship between aluminum potassium sulfate (APS) and memory deficits of mice. METHODS: 30, 60, or 90 d after the mice were given daily APS i.g., the step-through latency (STL) was determined with a passive avoidance task. Aluminum (Al) contents in brain and blood were assayed with atomic absorption spectrophotometry. Acetylcholine (ACh) content in brain was determined with chemiluminescent method and choline acetyltransferase (ChAT) activity was measured radiochemically. RESULTS: APS 1 g.kg-1 increased blood-Al only after 30 d. After 60 d, STL, ACh content and ChAT activity decreased by 46.4%, 8.5%, and 22.6%, respectively. These parameters decreased by 50%, 11.1%, and 27.8%, respectively, with increased Al in blood and brain, after 90 d. APS 0.25 g.kg-1 had no effects on mice except blood-Al. In ethylcholine mustard aziridium chloride (AF64A) treated mice, APS 1 g.kg-1 only increased blood and brain-Al. CONCLUSION: The intake of APS 1 g.kg-1.d-1 for 60 d induced learning and memory deficits in mice.

Acetylcholine↗
PubMed2004

The role of dopamine in learning, memory, and performance of a water escape task.

Dopamine-deficient (DD) mice have selective inactivation of the tyrosine hydroxylase gene in dopaminergic neurons, and they die of starvation and dehydration at 3-4 weeks of age. Daily injections of L-DOPA (50 mg/kg, i.p.) starting approximately 2 weeks after birth allow these animals to eat and drink enough for survival and growth. They are hyperactive for 6-9 h after receiving L-DOPA and become hypoactive thereafter. Because these animals can be tested in the presence or absence of DA, they were used to determine whether DA is necessary for learning to occur. DD mice were tested for learning to swim to an escape platform in a straight alley in the presence (30 min after an L-DOPA injection) or absence (22-24 h after an L-DOPA injection) of dopamine. The groups were split 24 h later and retested 30 min or 22-24 h after their last L-DOPA injection. In the initial test, DD mice without dopamine showed no evidence of learning, whereas those with dopamine had a learning curve similar in slope to controls but significantly slower. A retest after 24 h showed that DD mice can learn and remember in the absence of dopamine, leading to the inference that the lack of dopamine results in a performance/motivational decrement that masks their learning competence for this relatively simple task.

Analysis of Variance↗
PubMed2006

Effects of estradiol benzoate on learning-memory behavior and synaptic structure in ovariectomized mice.

There is increasing evidence that estrogen is involved in CNS activity, particularly memory. Several studies have suggested that estrogen improves memory by altering neuronal plasticity, including increased hippocampus CA1 dendritic spine density and enhanced long-term potentiation (LTP). In the present study, we investigated the effects of estrogen on the ultrastructural modifications in cerebral frontal cortex and hippocampus of female ovariectomized mice. One week after ovariectomy (Ovx), ICR female mice received daily injection of estradiol benzoate (EB, 20, 100, 200 microg/kg, s.c.) for 4-5 weeks. Spatial memory was then tested in the water maze, and the overall locomotor activity was monitored in open field. Synaptic morphologic parameters were examined using a graph analyzer. The results from open field did not show any alterations in locomotor activity following Ovx and EB replacement. Both the latency to find the platform and the distance to reach the platform were significantly reduced in Ovx mice by EB at 20 or 100 microg/kg when compared to vehicle treated Ovx mice. The results from synaptic ultrastructural measurement and analysis did not show any differences in hemispheric or hippocampal volumes, the numeric synaptic density, the length of active zones, or the curvature of synaptic interface among Sham, Ovx, and Ovx plus EB replacement mice. However, EB replacement effectively normalized the changes induced by Ovx, reducing the width of the synaptic cleft, enlarging the thickness of postsynaptic density (PSD), and increasing the number of synaptic vesicles in the presynapse in both cerebral cortex Fr1 and hippocampus CA1 areas. These results suggest that the beneficial effects of EB on improving memory behavior of Ovx female mice are associated with the changes of some subtle structural parameters of synapses, including the width of PSD and synaptic cleft rather than some basic and permanent structure in frontal cortex and hippocampus regions.

Animals↗
PubMed1978

[Effects of lithium on learning, memory, and mood (author's transl)].

In a double-blind study the effects of a 14-day lithium medication (dosage: 24 mval/d to 36 mval/d) were investigated. The subjects were 24 healthy male volunteers. The effect of lithium on their mood, ability to learn nouns, and memory of the words learnt was measured after 2 h and 14 days. In spite of a relatively low mean plasma lithium level on the 14th day (0.54 +/- 0.15 mmol/l), the lithium volunteers assessed themselves after 2 weeks of treatment as significantly less relaxed, less active, less socially involved, more bored, and more tired than the placebo group. As to learning, the lithium group showed only a slight impairment of performance compared to the placebo group. As to memory, there was only a significant difference in free recall over two weeks: the lithium group remembered fewer words than the placebo group. Additional motivation of free recall over 2 h was uneffective. It is discussed whether lithium changes spontaneous initial action and thereby the will to act. This could be interpreted as a change in the production of the characteristics of experience and behaviour.

Adult↗
PubMed2002

The effects of continuous versus partial reinforcement schedules on associative learning, memory and extinction in Lymnaea stagnalis.

A continuous schedule of reinforcement (CR) in an operant conditioning procedure results in the acquisition of associative learning and the formation of long-term memory. A 50 % partial reinforcement (PR) schedule does not result in learning. The sequence of PR-CR training has different and significant effects on memory retention and resistance to extinction. A CR/PR schedule results in a longer-lasting memory than a PR/CR schedule. Moreover, the memory produced by the CR/PR schedule is resistant to extinction training. In contrast, extinction occurs following the PR/CR schedule.

Animals↗
PubMed1979

Changes in learning, memory, and mood during lithium treatment. Approach to a research strategy.

In a double-blind study the effects of a 14-day lithium medication (dosage: 24 mval/day to 36 mval/day) were investigated. The subjects were 24 healthy male volunteers. The effect of lithium on their mood, ability to learn nouns, and memory of the words learnt was measured after 2 hours and 14 days. In spite of a relatively low mean plasma lithium level on the 14th day (0.54 +/- 0.15 mmol/l), the lithium volunteers assessed themselves after 2 weeks of treatment as significantly less relaxed, less active, less socially involved, more bored, and more tired than the placebo group. As to learning, the lithium group showed only a slight impairment of performance compared with the placebo groups. As to memory, there was a significant difference in free recall over 2 weeks: the lithium group remembered fewer words than the placebo group. Additional motivation of free recall over 2 hours was ineffective. It is discussed whether lithium changes spontaneous initial action and thereby the will to act. This could be interpreted as a change in the production of the characteristics of experience and behaviour.

Analysis of Variance↗
PubMed2005

Effects of category diversity on learning, memory, and generalization.

In this study, we examined the effect of within-category diversity on people's ability to learn perceptual categories, their inclination to generalize categories to novel items, and their ability to distinguish new items from old. After learning to distinguish a control category from an experimental category that was either clustered or diverse, participants performed a test of category generalization or old-new recognition. Diversity made learning more difficult, increased generalization to novel items outside the range of training items, and made it difficult to distinguish such novel items from familiar ones. Regression analyses using the generalized context model suggested that the results could be explained in terms of similarities between old and new items combined with a rescaling of the similarity space that varied according to the diversity of the training items. Participants who learned the diverse category were less sensitive to psychological distance than were the participants who learned a more clustered category.

Adolescent↗
PubMed1987

Cysteamine-induced depletion of central somatostatin-like immunoactivity: effects on behavior, learning, memory and brain neurochemistry.

The effects of a wide range of doses of systemically administered cysteamine were studied on locomotor behavior, passive avoidance memory, cortical and cerebrospinal fluid somatostatin-like immunoactivity and cortical levels of dopamine and norepinephrine. High doses of cysteamine (200 and 250 mg/kg s.c.) led to sustained locomotor activation. Doses of 150 mg/kg and above resulted in head and neck tremor and increased defecation. When cysteamine was administered immediately following the acquisition of a passive avoidance response, doses of 50 mg/kg and above resulted in significant attenuation of passive avoidance retention test performance. Cysteamine in doses of 50 mg/kg and above depleted cortical somatostatin-like immunoactivity by approximately 50%. The depletion of cortical somatostatin-like immunoactivity was accompanied by a rapid rise in somatostatin-like immunoactivity in cerebrospinal fluid. In addition to the depletion of somatostatin-like immunoactivity, high doses of cysteamine (150 mg/kg and above) produced changes in cortical levels of norepinephrine and dopamine, reminiscent of dopamine-beta-hydroxylase inhibition. The results of this series of experiments suggest that somatostatin, in addition to its effects on hormonal regulation, may play an important role in behavior and passive avoidance learning and memory. It is possible that the amnesia produced by cysteamine may have been due to the release of somatostatin into CSF from tissue stores, rather than somatostatin depletion per se. It is also possible that the catecholaminergic effects of high doses of cysteamine contribute to the behavioral deficits observed.

Animals↗
PubMed1997

The effects of lesions to thalamic lateral internal medullary lamina and posterior nuclei on learning, memory and habituation in the rat.

The behavioral effects of radiofrequency lesions to the lateral internal medullary lamina region (IML) or the posterior region (Po: containing the parafascicular and posterior nuclei) of the thalamus were compared to sham operated controls. Subjects were pre-operatively trained and then tested for post-operative retention of a NMTP task. Whereas the Po-lesion group was impaired only on long delays (60, 90 s), the IML-lesion group was impaired on retention and re-acquisition and demonstrated lower performance at all delays (5-90 s) of the NMTP task. Post-operative training and testing was conducted on three additional tasks: Morris water maze, acoustic startle, and passive avoidance. The IML-lesion group was impaired in finding a hidden and visual platform in the Morris water maze, demonstrated a blunted response but normal habituation to an acoustic startle stimulus, and showed normal retention of a passive avoidance task. On those three tasks, the performance of the Po-lesion group was similar to controls. In the IML-lesion group, neuronal loss resulting from axotomy and/or transneuronal degeneration was observed within nuclei of the midline and anterior thalamus and the mammillary body. These results suggest that lesions to the IML region disrupt a range of cognitive functions and produce pathological destruction in distant brain regions; whereas damage to the posterior thalamus causes spatial delay-sensitive deficits.

Animals↗