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Peripheral modulation of learning and memory: enkephalins as a model system.

Extensive research on the effects of enkephalins on conditioning is reviewed and used as the basis for a model of peripheral modulation of learning and memory. An overall theme emphasized throughout our discussion is that these peptides can influence the strength with which a memory is acquired and stored by acting outside the blood-brain barrier. This assertion is supported by research on the behavioral effects of systemically administered enkephalins and opioid antagonists, the rapid hydrolysis of circulating enkephalins in vivo, and the limited ability of these peptides to penetrate the blood-brain barrier. A consideration of the extensive distribution of enkephalins throughout peripheral autonomic systems leads to the proposal that enkephalins may act to modulate learning and memory by altering peripheral autonomic function; autonomic afferents may then communicate with the memory trace in the CNS through a central modulatory pathway outlined herein. Evidence that some stressful experiences may lead to increases in circulating enkephalins also is discussed. The sites of action of these circulating enkephalins may involve peripheral autonomic sites, or additionally may involve the circumventricular organs. As a further regulatory mechanism, circulating enkephalin levels may be controlled by experience-dependent alterations of the activity of enzyme systems that participate in their breakdown. Finally, it is emphasized that the mechanisms of enkephalin action postulated herein may be applicable to the actions of other peripheral hormones, peptides, and neurotransmitters that participate in the modulation of learning and memory storage processes.

Animals↗

Bridging behavior and physiology: ion-channel perspective on mushroom body-dependent olfactory learning and memory in Drosophila.

An important body of evidence documents the differential expression of ion channels in brains, suggesting they are essential to endow particular brain structures with specific physiological properties. Because of their role in correlating inputs and outputs in neurons, modulation of voltage-dependent ion channels (VDICs) can profoundly change neuronal network dynamics and performance, and may represent a fundamental mechanism for behavioral plasticity, one that has received less attention in learning and memory studies. Revisiting three paradigmatic mutations altering olfactory learning and memory in Drosophila (dunce, leonardo, amnesiac) a link was established between each mutation and the operation of VDICs in Kenyon cells, the intrinsic neurons of the mushroom bodies (MBs). In Drosophila, MBs are essential to the emergence of olfactory associative learning and retention. Abnormal ion channel operation might underlie failures in neuronal physiology, and be crucial to understand the abnormal associative learning and retention phenotypes the mutants display. We also discuss the only case in which a mutation in an ion channel gene (shaker) has been directly linked to olfactory learning deficits. We analyze such evidence in light of recent discoveries indicating an unusual ion current profile in shaker mutant MB intrinsic neurons. We anticipate that further studies of acquisition and retention mutants will further confirm a link between such mutations and malfunction of specific ion channel mechanisms in brain structures implicated in learning and memory.

Animals↗

Meta-analysis of sex differences in rodent models of learning and memory: a review of behavioral and biological data.

The existence of sex differences in the standard rat and mouse models of learning and memory is a controversial and contested topic in the literature. The present meta-analysis of radial maze and water maze experiments was conducted to assess the reliablility and magnitude of sex effects in the standard rodent models of learning and memory. Data were culled from published and unpublished sources. Findings indicate large reliable male advantages for rats in radial maze and water maze protocols. Significant strain differences were also identified. In each paradigm, protocol variations were associated with differential sex effects. For the water maze, smaller male advantages were associated with pretraining regimens and for the radial maze, larger significant male advantages were observed in protocols that included unbaited arms (combined reference and working memory protocols). Mouse studies exhibited a different pattern of sex effects; small female advantages were evident in the water maze, but small male advantages were evident in the radial maze. Together these findings establish the reliability of male advantages in spatial working and reference memory for rats across strains, protocols, ages and rearing environments. The findings also support an important species dichotomy between rats and mice that should be considered when transitioning from rat to mouse models. In light of these results, the biological evidence supporting theoretical explanations of sex differences is reviewed and evaluated.

Animals↗

Differential modulation of the 5-HT(4) receptor agonists and antagonist on rat learning and memory.

Recent data suggest that activation of 5-HT(4) receptors may modulate cognitive processes such as learning and memory. In the present study, the effects of two potent and selective 5-HT(4) agonists, RS 17017 [1-(4-amino-5-chloro-2-methoxyphenyl)-5- (piperidin-1-yl)-1-pentanone hydrochloride] and RS 67333 [1(4-amino-5-chloro-2-methoxyphenyl)-3- (1-n-butyl-4-piperidinyl)-1-propanone], were studied in an olfactory associative discrimination task. The implication of 5-HT(4) receptors in the associative discriminative task was suggested by the following observation. Injection of a selective 5-HT(4) receptor antagonist RS 67532 [1-(4-amino-5-chloro-2-(3, 5-dimethoxybenzyloxyphenyl)-5-(1-piperidinyl)-1-pentanone; 1 mg/kg: i.p.] before the third training session induced a consistent deficit in associative memory during the following training sessions. This deficit was absent when the antagonist was injected together with either a specific hydrophilic 5-HT(4) (RS 17017, 1 mg/kg) or a specific hydrophobic (RS 67333, 1 mg/kg) 5-HT(4) receptor agonist. RS 67333 was more potent than RS 17017. This difference in potency certainly reflects a difference in their capacity to enter into the brain. This is also likely to be the reason why, injected alone, the hydrophobic 5-HT(4) agonist (RS 67333) but not the hydrophilic 5-HT(4) agonist (RS 17017) improved learning and memory performance.

Aniline Compounds↗

Learning and memory of school children with epilepsy: a prospective controlled longitudinal study.

The aim of the study was to determine whether learning and memory are compromised in school children with recently diagnosed idiopathic and/or cryptogenic epilepsy and to study relationships between learning and memory and psychosocial and epilepsy variables. Word span and learning of locations were assessed within 48 hours after diagnosis of epilepsy and three and 12 months later, in 69 school children with epilepsy (aged 9.1 years, SD 2.7; 33 males, 36 females) and 66 classmates. Results showed that patients and controls performed similarly in registration, recall, and retention. Patients recalled slightly less than controls when probed under conditions of increased demand on working memory. Maladaptive reactions of parents and children to the onset of epilepsy and not reaching 6-months of seizure remission contributed to poor performance. Individually, those patients who required special assistance at school, under-performed occasionally in one or the other component of memory. Although the proportion of under-performers was stable over time, the children composing the group did change. It was concluded that school children with new onset idiopathic or cryptogenic epilepsy are inordinately vulnerable when processing memory tasks. The vulnerability is neither persistent nor memory-specific.

Child↗

Anastrozole improved testosterone-induced impairment acquisition of spatial learning and memory in the hippocampal CA1 region in adult male rats.

Neurohormones like testosterone and estrogen have an important role in learning and memory. Many biological effects of androgens in the brain require the local conversion of these steroids to an estrogen. The current research has conducted to assess the effect of testosterone, estrogen and aromatase inhibitor (anastrozole) on spatial discrimination of rats, using Morris water maze and also the pathway of the effect of testosterone by using anastrozole. Adult male rats were bilaterally cannulated into CA1 region of hippocampus and divided into 15 groups. Different groups received DMSO 0.5 microl and DMSO 0.5 microl + DMSO 0.5 microl as control groups and different doses of testosterone enanthate (TE) (20, 40 and 80 microg/0.5 microl), estradiol valerat (EV) (1, 2.5, 5, 10, and 15 microg/0.5 microl), anastrozole (An) (0.25, 0.5, 1 microg/0.5 microl), TE 80 microg/0.5 microl + anastrozole 0.5 microg/0.5 microl and EV 15 microg/0.5 microl + anastrozole 0.5 microg/0.5 microl all days before training. TE and EV were injected 30-35 min before training and anastrozole was injected 25-30 min before training. Our results have shown both TE 80 microg/0.5 microl and EV 15 microg/0.5 microl groups increase in escape latency and traveled distance to find invisible platform. Also we have shown that anastrozole dose dependently decreases escape latency and traveled distance. We resulted that both TE and EN impaired acquisition of spatial learning and memory but anastrozole improved it. Anastrozole also could be buffered TE-induced impairment effect but not EV.

Analysis of Variance↗

Investigations of hypesthesia: using anesthetics to explore relationships between consciousness, learning, and memory.

This paper discusses the ways in which anesthetic agents can be used to investigate the role of awareness in learning and memory. It reviews research into learning during light, subclinical anesthesia, termed hypesthesia. This research suggests that the effects of anesthetics on implicit and explicit memory are roughly comparable, although implicit memory for simple stimuli may resist the effects of very low doses of anesthetic. In addition, this paper reports experimental data demonstrating that long-term retention of information is prevented by doses of anesthetic that are low enough to permit awareness and even shortterm memory of auditory stimuli. Overall, these findings are consistent with the hypothesis (e.g., Caseley-Rondi, 1996) that frontal lobe function is particularly sensitive to anesthetics. They raise theoretical and practical questions about the necessity of consciousness for learning and about interpretation of the evidence for learning during surgery under general anesthesia.

Anesthesia, General↗

[Experimental study of the effects of amiridin and tacrine on learning and memory].

The authors studied the influence of amiridin and tacrine on learning and memory in mice and rat by passive avoidance conditioning test at norm and under scopolamine induced amnesia as well as of their effect on acetylcholine esterase (AChE) activity in brain cortex homogenates. Amiridin in doses 0.1 and 0.2 mg/kg showed a beneficial action on conditioning in untreated animals, its effect being comparable with that of piracetam. Tacrine was ineffective. In scopolamine treated animals amiridin and tacrine showed anti-amnestic action at dose of 0.1 mg/kg which was found ineffective with respect to AChE activity. The data suggests that the ameliorating effect of amiridin and tacrine on cognitive abilities in patients with senile dementia is not related their anticholinesterase properties.

Acetylcholinesterase↗

Effects of central nicotinic cholinergic receptor blockade produced by chlorisondamine on learning and memory performance in rats.

The effects of chronic nicotinic receptor blockade on the performance of learning and memory tasks were determined using chlorisondamine, a compound which produces central nicotinic cholinergic receptor blockade that lasts for several weeks after a single icv administration. Chlorisondamine treatment did not affect the acquisition of spatial information in the Morris water maze or in the radial arm maze, tasks in which performance is reportedly disrupted by acute administration of the nicotinic antagonist, mecamylamine. Chlorisondamine also did not affect performance in the inhibitory avoidance task and did not alter the memory enhancement found in this task after post-training administration of nicotine. Mecamylamine, however, completely blocked the memory-enhancing effects of nicotine. In contrast to the differential ability to chlorisondamine and mecamylamine to block nicotine's memory-enhancing effects, these antagonists produced comparable blockade of nicotine's effects on open field behavior. It is unlikely that the different effects of systemically administered mecamylamine and centrally administered chlorisondamine on nicotine-induced memory enhancement are due to mecamylamine's peripheral effects, since hexamethonium, a peripherally active nicotinic antagonist, did not block nicotine-induced memory enhancement. The different pattern of effects of mecamylamine and chlorisondamine may be related to compensatory mechanisms being selectively induced by chronic blockade produced by chlorisondamine and not by acute blockade produced by mecamylamine. Alternatively, different effects of these two nicotinic cholinergic antagonists on the performance of learning and memory tasks might be related to selective actions of these compounds at nicotinic receptor subtypes or at nonnicotinic receptors.

Animals↗

Behavioral compensations in a positional learning and memory task by aged monkeys.

The present experiment assessed learning and memory of a positional task by evaluating behavioral strategies as well as accuracy of a task in four young and four aged monkeys. They were tested in a delayed response (DR) task that has been widely used to study animal models of aging. The task consisted of two phases; an acquisition of the task and a positional memory test with five delay times (1-30 s). There was no clear difference between age groups in the number of trials needed for acquisition of the task. However, an analysis of behavior revealed differences in behavioral characteristics displayed during testing. The young monkeys showed various irrelevant behaviors during the execution of the task. In contrast, the aged monkeys consistently concentrated on the task exhibiting no behaviors irrelevant to the task. These results showed than the aged monkeys' performance was supported by a different behavioral strategy from the young monkeys. The results of the memory test were similar to those of the acquisition on the accuracy and the behavior. The aged monkeys depended on behavioral cues to preserve their positional memory, especially during the task. The present study suggests that cognitive impairments in aged monkeys can be compensated for by employing behavioral strategies.

Journal Article↗

The relationship between learning disability, intelligence, and paired-associate learning.

Learning disabled (N = 45) and non-learning disabled (N = 39) third and fourth grade boys and girls were compared in four paired-associate situations. The situations respectively measured learning, memory, exemplar learning, and transfer. Intelligence was measured with the WISC-R. The data were nonnormal in distribution, and the results were thus analyzed parametrically for intelligence and group. What appears to be an interaction occurred. Intelligence facilitated performance for normals on the memory task but had a deleterious effect for the learning disabled Ss. The learning disabled high intelligence group, however, performed significantly better than the other groups on the exemplar and transfer tasks. These findings are discussed in terms of conceptualizations of learning disability and the nature of intervention strategies. In addition, concern is raised for the validity for research with these children where the IQ factor is ignored or covaried and not directly investigated.

Child↗

Learning and memory impairment in patients with temporal lobe epilepsy: relation to the presence, type, and location of brain lesion.

PURPOSE: To study the influence of epileptogenic lesions on learning and memory alterations in patients with temporal lobe epilepsy (TLE). METHODS: We studied 131 patients (55 with left and 39 with right lesional TLE; 22 with left and 15 with right cryptogenic TLE) and 36 healthy subjects. We compared these groups by using a battery of tests to assess verbal and visual learning, delayed recall, and recall after the imposition of interfering activity. RESULTS: Compared with the controls and patients with right TLE, the patients with left TLE were significantly impaired on all verbal tests. On visual tests, patients with right TLE were impaired compared with controls but not more so than patients with left TLE. Separate multivariate analyses of variance (MA-NOVAs) of patients' verbal and visual test scores, taking the TLE side and morphologic features of the temporal lobes (i.e., normal, hippocampal sclerosis, low-grade glioma, or cavernous angioma) as independent factors, did not show any significant effect of these features. Separate comparisons of verbal and visual test scores of patients with lesional TLE, taking the side and location (mesial or lateral) of the epileptogenic lesion as independent factors, did not show any significant effect of location. CONCLUSIONS: Our findings show that some learning and memory abilities are impaired in patients with TLE irrespective of the presence of overt damage. This supports the theory that focal epileptic discharges, rather than the lesions themselves, affect these functions. The pathologic characteristics and intratemporal location of an associated lesion do not seem to play an important role in determining learning and memory impairment when clinical and treatment-related factors are taken into account.

Brain Diseases↗

Changes in learning and memory, acetylcholinesterase activity and monoamines in brain after chronic carbamazepine administration in rats.

Groups of adult male Wistar rats were administered carbamazepine (CBZ) in doses of 5, 10, 20, 40 or 80 mg/kg/day intraperitoneally (i.p.) for 21 days. The learning and memory of the rats were assessed by the T-maze and passive avoidance tests. The CBZ plasma levels, the activity of acetylcholinesterase (AChE) in different brain regions, and the levels of monoamines in the hippocampus were also measured. None of the administered doses of CBZ impaired learning and memory. Rats with CBZ plasma levels of 2.5 and 4.5 micrograms/ml corresponding to the doses of 20 and 40 mg/kg, learned significantly better than controls. AChE activity was decreased in hippocampus and pyriform cortex (19%) in these groups. Simultaneously, an increase in the serotonin (5-HT) (36%) and dopamine (137%) levels in the hippocampus was noted in the 20-mg/kg CBZ group. 5-Hydroxyindole acetic acid (5-HIAA) and homovanillic acid (HVA) levels were increased at 10-, 20-, and 40-mg/kg CBZ doses. However, a dose of 80-mg/kg caused no change in learning performance as compared with that of controls. Correspondingly, no changes were evident in the AChE activity or monoamine levels. We postulated that the decreased AChE activity caused by CBZ in the therapeutic range may lead to increased ACh levels in brain, thus producing improvement in learning and memory. The increased turnover of 5-HT and dopamine (DA) in the hippocampus may play a role in long-term potentiation and improvement in memory.

Acetylcholinesterase↗

[Gly(14)]-Humanin improved the learning and memory impairment induced by scopolamine in vivo.

Humanin is a very recently discovered 24 amino acid linear polypeptide, which protects against cell death induced by either familial Alzheimer's disease mutant of amyloid precursor protein, presenilin-1 or presenilin-2 in vitro. However, it has remained uncertain whether humanin is a useful drug for the animal model of learning and memory deficit. In this study, we evaluated the effects of [Gly(14)]-humanin, a more potent humanin analogue, on the scopolamine HBr (1 mg kg(-1) s.c.)-induced impairment of spontaneous alternation behaviour in the Y-maze, an index of short-term memory in mice. [Gly(14)]-Humanin (1000 pmol 5 microl(-1) i.c.v.) reversed the impairment without affecting the number of arm entries. These results suggest that (I) [Gly(14)]-humanin is a beneficial drug for the impairment of learning and memory and (II) it modulates the learning and memory function mediated via cholinergic systems in mice.

Amino Acid Sequence↗

Varieties of learning and memory in animals.

It is often assumed that there is more than one kind of learning--or more than one memory system--each of which is specialized for a different function. Yet, the criteria by which the varieties of learning and memory should be distinguished are seldom clear. Learning and memory phenomena can differ from one another across species or situations (and thus be specialized) in a number of different ways. What is needed is a consistent theoretical approach to the whole range of learning phenomena, and one is explored here. Parallels and contrasts in the study of sensory systems illustrate one way to integrate the study of general mechanisms with an appreciation of species-specific adaptations.

Animals↗

[The effect of N-acetylaspartic acid on the processes of memory and learning in rats].

The effects of a neurospecific substance N-acetyl-aspartic acid on memory and learning processes were investigated after intraperitoneal and oral administrations in rats. N-acetyl-aspartic acid was shown to restore the passive avoidance reaction in electroshock and scopolamine amnesias as well as in natural extinction. Chronic injections of N-acetyl-aspartic acid improved the learning in water maze but exerted no effect on the acquisition and retention of the active avoidance reaction in the shuttle box.

Amnesia↗

[Learning and memory: neurophysiological mechanisms].

The analytical review of study of neurophysiological basis in different kinds of learning and memory in animal and human is given. The main attention is paid to the consideration of systemic and neuronal levels of habituation and conditioned reflexes. A conception on the brain functional state as the main mechanisms of learning and distributed multicomponent engram corresponding to the integrative process peculiarities is developed.

Animals↗

Caenorhabditis elegans: a new model system for the study of learning and memory.

The extensive information on the neuroanatomy, development and genetics of Caenorhabditis (C.) elegans make it an ideal candidate model system for the analysis of the mechanisms underlying learning and memory. A first step in this analysis is the demonstration of the capacity of C. elegans to learn. In these experiments non-associative learning in C. elegans was investigated by observing changes in reversal reflex response amplitude to a mechanical vibratory stimulus. The results from these studies of non-associative learning show that C. elegans is capable of short-term habituation, dishabituation and sensitization, as well as long-term retention of habituation training lasting for at least 24 h. These findings set the stage for detailed developmental, genetic and physiological analyses of learning and memory.

Animals↗