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PubMedDate not supplied

What is the nature of the role of the serotonergic nervous system in learning and memory: prospects for development of an effective treatment strategy for senile dementia.

The serotonergic nervous system has long been suspected of playing an important role in the processes underlying learning and memory. However, owing frequently to inconsistent and divergent results, its precise role is difficult to define. Recently, there has been a renewed interest in this neurotransmitter's role in the processes underlying learning and memory. This has, in part, been due to the observations that this system appears to undergo significant deterioration as a result of the pathology associated with certain age-related cognitive disorders as well as the discovery of multiple receptor subtypes. Reviewed here are the results of a number of studies designed to gain further insight into the role the serotonergic nervous system plays in learning and memory. A variety of methods are used to manipulate this system, and the effects of these manipulations on performance in a variety of behavioral tasks are summarized. Consistent with past observations, it is difficult to incorporate the results of the present series of studies into a single unified theory of serotonin's role in learning and memory. However, it is clear that not all of the inconsistencies can be attributed to differences in the methods used to manipulate the system or in the types of tasks used to assess learning and memory. Some of the inconsistencies clearly belie a selective role of this neurotransmitter in the processes underlying learning and memory and further underscore the complex nature of this system's role in the processing of information by the brain.

Dementia↗

PubMed2005

[Effects of prenatal methylmercury exposure on learning and memory ability of mice and ultrastructure of hippocampus neurons in mice].

OBJECTIVE: To study the effects of prenatal methylmercury exposure on learning and memory ability of mice and ultrastructure of hippocampus neurons in mice. METHODS: Methylmercury in doses of 0 and 4mg/(kg x d) were fed to pregnant mice at 7th-9th day after conception. Learning and memory ability of the mice offspring was detected. The ultrastructure of hippocampus neurons was observed by electron microscope after the completion of the experiment. RESULTS: The learning and memory ability of the mice offspring of 4 mg/(kg x d) dose group was lower than those of 0 mg/(kg x d) dose group (P < 0.05). Changes in the ultrastructure of hippocampus neurons were obvious in 4 mg/(kg x d) dose group as compared with the 0 mg/(kg x d) dose group. CONCLUSION: Methylmercury could affect the growth and development of central nerve system. The learning and memory ability of mice offspring was greatly damaged and the ultrastructure of hippocampus neurons was changed by methylmercury.

Animals↗

PubMed2000

[Effects of tail suspension on learning and memory function of mice].

Objective. To study the effects of simulated weightlessness on learning and memory capability of the brain. Method. Accuracy fraction, error frequency and pass rate were observed among control, restrained control, tail suspended (TS) control, restrained, and tail suspended mice in square water maze tests. And latent period and error time were observed in control and 30 degrees tail suspension mice in step down test. Result. The indices did not change significantly during learning period. Accuracy fraction of tail suspended group was reduced significantly in the tests as compared with pretest values. In step down test, latent period and error time showed no difference between TS 5 h and 2 d in untrained mice, but shortened evidently after TS 2 d and prolonged after TS 7 d in trained mice, which suggested the degradation of learning and memory ability after TS 5 h and 2 d respectively. Conclusion. Acute tail suspension depressed brain's learning ability and quality, while tail suspension of 7 d and 12 d impaired the spatial memory in mice.

Animals↗

PubMed1995

Verbal learning and memory following pediatric closed-head injury.

In this study, verbal learning and memory following pediatric closed-head injuries (CHI) using the children's version of the California Verbal Learning Test (CVLT). Participants included 47 children, ages 5-16 yr, with a history of CHI, and 47 matched, noninjured controls. Children with CHI performed more poorly than controls on the CVLT, although their deficits varied qualitatively as a function of injury severity. Those with mild/moderate injuries performed as well as controls on learning trials, but they recalled proportionally fewer words after a delay (although their recognition was intact). Severely injured children demonstrated deficits in learning, delayed recall, and recognition, compared to controls. The groups did not differ in learning characteristics, but children with severe CHI exhibited more intrusions than controls. Pediatric CHI are associated with specific disturbances in verbal learning and memory similar to those of adults with CHI but different from those of children with other developmental and neurological disorders.

Adolescent↗

PubMed1989

In vivo protein phosphorylation in Drosophila mutants defective in learning and memory.

Polypeptides phosphorylated in vivo in Drosophila mutants defective in learning and memory, were characterized by polyacrylamide gel electrophoresis of subcellular fractions obtained by phase partitioning in Triton X-114 [3]. In the mutants turnip, dunce and Shaker, one or more bands at a molecular weight range of 50-80 kDa had altered 32P incorporation. Some of these bands were altered in more than one mutant. In the mutant rutabaga no significant differences from wild-type were observed. The data suggest that phosphoproteins that could be potentially related to learning mechanisms might be identified in some learning mutants.

Animals↗

PubMed2002

Extract of Yi Zhi Fang improves learning and memory behaviours of mice and its possible mechanisms.

The effects of Yi Zhi Fang extract (YZF) on learning and memory performances were investigated in mice using passive avoidance tasks. Oral administration of YZF improved learning and memory disorders induced by chemicals in both normal and senile mice. The acetylcholine (Ach) concentration, the muscarinic Ach receptors (M-R) and the monoamine oxidase B (MAO-B) activities were analysed by a radioimmunoassay, a radioligand receptor binding assay and UV spectrophotometry, respectively, using senile decapitated mice. The oral administration of YZF to the senile mice increased the M-R concentration, while the concentration of Ach and the activity of MAO-B decreased in senile mice brains. From these results it is evident that YZF promotes the function of the central cholinergic system and inhibits the activity of MAO-B in mice brains resulting in an enhancement of learning and memory.

Acetylcholine↗

PubMed2004

Characteristics of non-verbal memory impairment in bipolar disorder: the role of encoding strategies.

BACKGROUND: There is evidence that individuals with bipolar disorder exhibit neuropsychological impairments not only during episodes of depression or mania but also when they are euthymic. One of the most consistently reported cognitive problems in euthymic individuals with bipolar disorder is impairment in episodic memory. Learning and memory depend on individuals' ability to organize information during learning. A recent study by our group showed that verbal episodic memory impairments in euthymic patients with bipolar I disorder (BP-I) are mediated by difficulties in organizing verbal information appropriately during learning. The purpose of the present study was to determine whether memory impairments in euthymic individuals with BP-I extend to non-verbal memory and whether non-verbal memory impairments are mediated by difficulties in organizing non-verbal information during encoding. METHOD: Study participants were 25 euthymic, remitted individuals with BP-I and 25 age, gender and education matched control participants. Participants completed the Rey-Osterrieth Complex Figure Test (RCFT), a well-established measure of non-verbal memory that enables assessment of organization during learning. RESULTS: Compared to control participants, BP-I participants showed impaired performance on the RCFT immediate recall. They also relied less on organizational strategies during encoding. Multiple regression modeling indicated that group differences between control and BP-I participants in long-delayed free recall did not remain statistically significant when effects of lower organization were partialled out. CONCLUSIONS: Non-verbal memory problems in individuals with bipolar disorder, while euthymic, are mediated by poor use of non-verbal organization strategies during encoding, but do not appear to reflect deficits in retention of information.

Adult↗

PubMed1989

Strategies for assessing learning and memory, 1978-1987: a comparison of behavioral toxicology, psychopharmacology, and neurobiology.

Tests of learning and memory are currently not typically included in first-tier screening batteries even though there is ample evidence that chemical exposure can produce deficits in these cognitive processes. The approach taken in behavioral toxicology has been to restrict these cognitive tests to second tier or hazard characterization studies, yet there is little agreement on which tests are most appropriate. The present survey was designed to determine the current testing strategies in toxicology for detecting and characterizing the effects of chemical treatment on learning and memory, and to make comparisons to similar data from the fields of psychopharmacology and neurobiology. The survey data revealed a number of discipline-dependent effects on the selection of tests. A number of these effects were clearly related to the subject matter as well as the particular chemical/treatment being examined. Given the youth of the field, behavioral toxicology has the advantage of gaining valuable information from both of these disciplines. Behavioral testing in neurotoxicology should consider strategies which maximize unification of these closely related fields of neuroscience.

Animals↗

PubMedDate not supplied

[The psychobiology of learning and memory: fundamentals and recent advances].

AIM: This review describes the concepts, temporal dynamics and main features of learning and memory systems from a comprehensive molecular, neuroanatomical, neurophysiological, cognitive and behavioural approach. DEVELOPMENT: Starting with molecular mechanisms of synaptic plasticity we describe the memory stages, implicit and explicit memory systems, working memory, remembering and forgetting. Each process is illustrated with examples of recent experimental and clinical research. CONCLUSIONS: Learning and memory are closely related brain processes which give rise to adaptive changes in behaviour. Implicit memory is a kind of unconscious and rigid memory for habits, which is based on brain regions processing perceptions and motor and emotional information, like the neocortex, the neostriatum, the cerebellum or the amygdala. Explicit or declarative memory is a conscious and flexible memory, hippocampus-dependent. Working memory is actually a system of executive cognition, based on interactions between the prefrontal cortex and other brain regions. The retrieval of complex memories consist of an active process of reconstruction of the past which incorporates new experiences of the subject who is remembering. The reactivation of memories can initiate genuine processes of reconsolidation and extinction. Forgetting could depend on alterations in the neural networks storing the information or, otherwise, on active processes which hinder consolidation or block the expression of the memories.

Animals↗

PubMed2003

Handling and environmental enrichment do not rescue learning and memory impairments in alphaCamKII(T286A) mutant mice.

Environmental enrichment and postnatal handling have been shown to improve learning and memory in the Morris water maze, and to rescue impairments caused by genetic modification, age or genetic background. Mice with a targeted point mutation that prevents autophosphorylation at threonine-286 of the alpha-isoform of the Ca2+/calmodulin-dependent kinase II have impaired hippocampus-dependent and -independent strategy learning and memory in the water maze. We have investigated whether these impairments can be rescued with a combination of postnatal handling and environmental enrichment in a hybrid genetic background. Severe impairments were seen in acquisition and probe trials in both enriched and nonenriched mutants, indicating that enrichment did not rescue the learning and memory impairments. However, enrichment did rescue a specific performance deficit; enhanced floating behaviour, in the mutants. In summary, we have shown the lack of autophosphorylation of the alpha-isoform of the Ca2+/calmodulin-dependent kinase II prevents enrichment-induced rescues of strategy learning and memory impairments. Furthermore, we have established that there are enrichment mechanisms that are independent of this autophosphorylation.

Animals↗

PubMed1999

Transcranial magnetic stimulation can measure and modulate learning and memory.

The potential uses for Transcranial Magnetic Stimulation (TMS) in the study of learning and memory range from a method to map the topography and intensity of motor output maps during visuomotor learning to inducing reversible lesions that allow for the precise temporal and spatial dissection of the brain processes underlying learning and remembering. Single-pulse TMS appears to be adequate to examine motor output maps but repetitive TMS (rTMS) appears necessary to affect most cognitive processes in measurable ways. The results we have reviewed in this article indicate that rTMS may have a potential clinical application in patients with epilepsy in whom it is important to identify the lateralization of verbal memory. Single-pulse TMS can help identify changes in motor output maps during training, that may indicate improved or diminished learning and memory processes following a stroke or other neurological insult. Other evidence indicates that rTMS may even have the capability of facilitating various aspects of memory performance. From a research perspective. rTMS has demonstrated site- and time-specific effects primarily in interfering with explicit retrieval of episodic information from long-term memory. rTMS may also be able to modulate retrieval from semantic memory as evidenced by response-time and accuracy changes after rTMS. All these findings suggest that the use of transcranial magnetic stimulation in the study of learning and memory will increase in the future and that it is already a valuable tool in the cognitive neuroscientists' belt.

Blinking↗

PubMed2002

Multiple injections of thyrotropin releasing hormone fail to reverse learning and memory deficits in rats with lesions of the nucleus basalis of meynert.

The learning and memory enhancing effects of thyrotropin releasing hormone (TRH) was examined in an animal model of Alzheimer's disease. Adult rats were prepared with either sham surgeries or cholinergic lesions of the nucleus basalis of Meynert (nbM). Subjects were injected (ip) with one of three doses of TRH (0, 5, 10 mg/kg) starting on the day of surgery and continuing once every other day for a total of four injections. Performance (four trials/day for 4 days, 30 m inter-trial interval) in a Morris water maze was assessed one week after the last TRH injection (i.e., 2 weeks postoperatively). Latency to find the hidden platform served as the dependent variable. Results indicated that damage to the nbM impaired task performance in that animals with nbM lesions generally required more time to find the platform and showed less trial-to-trial improvement. Treatment with TRH failed to reverse this lesion-induced deficit. These results suggest that multiple injections of TRH do not provide residual protection against the deleterious effects on learning and memory produced by cholinergic lesions of the basal forebrain. Other doses and administration parameters, however, need to be studied in order to determine the generalizability of these findings.

Alzheimer Disease↗

PubMed2002

Mice deficient for the HNK-1 sulfotransferase show alterations in synaptic efficacy and spatial learning and memory.

The HNK-1 carbohydrate structure, a sulfated glucuronyl-lactosaminyl residue carried by many neural recognition molecules, is involved in cell interactions during ontogenetic development and in synaptic plasticity in the adult. To characterize the functional role of the HNK-1 carbohydrate in vivo, we have generated mice deficient for the HNK-1 sulfotransferase (ST). The ST-/- allele is inherited with Mendelian frequencies, and the ST-/- mice are viable and fertile. The anatomy of all major brain areas appeared histologically normal. However, basal synaptic transmission in pyramidal cells in the CA1 region of the hippocampus was increased and long-term potentiation evoked by theta-burst stimulation was reduced in ST mutants. In the water maze, ST-/- mice showed an impaired long-term memory and a poorer spatial learning when a short inter-trial interval was used. These observations indicate an essential role for the sulfate group of the HNK-1 carbohydrate in synaptic plasticity of the hippocampus.

Animals↗

PubMed2001

Conditional rescue of olfactory learning and memory defects in mutants of the 14-3-3zeta gene leonardo.

Members of the ubiquitous 14-3-3 family of proteins are abundantly expressed in metazoan neurons. The Drosophila 14-3-3zeta gene leonardo is preferentially expressed in adult mushroom bodies, centers of insect learning and memory. Mutants exhibit defects in olfactory learning and memory and physiological neuroplasticity at the neuromuscular junction. Because strong mutations in this gene are lethal, we investigated the nature of the defects that precipitate the learning and memory deficit and the role of the two protein isoforms encoded by leonardo in these processes. We find that the behavioral deficit in the mutants is not caused by aberrant development, LEONARDO protein is acutely required for learning and memory, and both protein isoforms can function equivalently in embryonic development and behavioral neuroplasticity.

14-3-3 Proteins↗

PubMed1995

The effects of anxiolytics and anxiogenics on evaluation of learning and memory in an elevated plus-maze test in mice.

We examined the effects of anxiolytics and anxiogenics on evaluation of learning and memory in the elevated plus-maze test in mice. Transfer latency (TL), the time mice took to move from the open arm to the enclosed arm, was used as an index of learning and memory. The TL on day 2 was shorter than that on day 1 with the maze at a height of 40 cm, and was not affected by anxiolytics and anxiogenics such as 8-OH-DPAT (0.4 mg/kg), picrotoxin (2 mg/kg), and FG-7142 (20 mg/kg), but was affected by diazepam (8 mg/kg). On the other hand, the TL on day 2 was prolonged by changing the experimental room between day 1 and day 2. TL on day 1 and day 2. TL on day 2 was prolonged by treatment with scopolamine before the trial on day 1 compared with vehicle-treated groups. This scopolamine-induced prolongation of TL was reversed by pretreatment with physostigmine and piracetam. The TL on day 2 was also prolonged by treatment with cycloheximide or normobaric hypoxia initiated immediately after the trial on day 1. The cycloheximide- and hypoxia-induced prolongation of TL were reversed by pretreatment with piracetam. These results indicate that disruption of learning and memory and its amelioration, induced by the treatments described above, can be detected using the plus-maze test, suggesting that the elevated plus-maze test could be used for evaluation of learning and memory without influence of anxiolytics and anxiogenics.

Animals↗

PubMed1998

Learning and memory of rats after long-term administration of low doses of parathion.

A set of four learning and memory tests (Morris Maze I for reference memory, Morris Maze II for working memory, one-way active avoidance, and passive avoidance) were employed to address the questions whether parathion impaired cognitive functions after low, long-term exposure and could cause persistent changes in cognition. Motor activity and general behavior were investigated in a functional observational battery. Parathion was administered in rat food in low doses which caused no clinical symptoms and no or borderline brain acetylcholinesterase inhibition. Parathion doses of 0.5, 2, or 8 ppm in rat food produced the averaged uptake of 24, 100, or 400 microg/kg body weight per group per day in male rats and 36, 152, or 550 microg/kg per day in female rats in week 13. Learning tests were performed in weeks 1 to 4 and 10 to 14, as well as 30 to 34 weeks after the end of treatment, when the male and female rats were about 13 months old. Low doses of parathion given daily for 13 weeks had no cumulative or adverse effects on learning and memory, either during treatment or after the extended treatment-free period, in any of the tests. A significant improvement of learning compared to control observed in the Morris Water Maze I during the first week of treatment (males dose group 0.5 ppm) shows that parathion can improved cognitive functions in rats. Results of the study indicate that adverse effects changing learning and memory in animals may occur only at higher doses of organophosphates, at which the peripheral and brain acetylcholinesterases are inhibited to a greater extent than those in the present study.

Animals↗

PubMed1997

Interactions between nitric oxide and dopamine in inhibitory learning and memory in newborn rats.

Taking into account our previous results on dopamine and nitric oxide effects on neonatal inhibitory learning and memory in rats, the mutual interactions of the two molecules were studied in this experimental paradigm. Both increased dopamine content and nitric oxide bioavailability in the brain after application of dopamine and L-arginine as substrate for nitric oxide synthase solutions into lateral cerebral ventricles improved learning and 24 h memory. Joint application of dopamine and L-arginine yielded still more improvement. Learning and memory processing were dose dependently enhanced by D1 receptor agonists as well, whereas D1 receptor antagonists had an opposite and also dose-dependent effect. Dopamine or D1 receptor agonists administered together with nitro-L-arginine, a nitric oxide synthase inhibitor that impaired learning and memory due to a decreased nitric oxide availability, antagonized the effect of nitro-L-arginine, as did L-arginine. D1 receptor antagonists impaired both learning and memory, and L-arginine rendered learning values normal. The dopamine and D1 receptor-agonist effect on 24 h memory was concentration dependent, and their higher concentrations substantially increased the retention indexes. The intimate mechanisms of these interactions are to be identified in further experiments.

Animals↗

PubMed2002

Gene expression profiles--a new dynamic and functional dimension to the exploration of learning and memory.

Many experiments in the past have demonstrated the requirement of de novo gene expression during the long-term retention of learning and memory. Although previous studies implicated individual genes or genetic pathways in learning and memory they did not uncover the collective behaviors of the genes. In view of the broad variety of genes and the cross-talk of genetic pathways, gene expression profiles offer a new dynamic and functional dimension to the exploration of learning and memory. This review illustrates how DNA microarray-based gene expression profiling may help to dissect and analyze the complex mechanisms involved in gene regulation during the acquisition and storage of memory.

Animals↗