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Differential effects of learning on neurogenesis: learning increases or decreases the number of newly born cells depending on their birth date.

The hippocampal formation, to which new neurons are added on a daily basis throughout life, is important in spatial learning. Surviving de novo produced cells integrate into the functional circuitry, where they can influence both normal and pathological behaviors. In this study, we examined the effect of the water-maze (a hippocampal-dependent spatial task) on neurogenesis. Learning in this task can be divided into two phases, an early phase during which performance improves rapidly, and a late phase during which asymptotic levels of performance are reached. Here we demonstrate that the late phase of learning has a multifaceted effect on neurogenesis depending on the birth date of new neurons. The number of newly born cells increased contingently with the late phase and a large proportion of these cells survived for at least 4 weeks and differentiated into neurons. In contrast, late-phase learning decreased the number of newly born cells produced during the early phase. This decline in neurogenesis was positively correlated with performance in the water-maze. Thus, rats with the highest de novo cell number were less able to acquire and use spatial information than those with low numbers of new cells. These results show that learning has a complex effect on hippocampal neurogenesis, and reveals a novel mechanism through which neurogenesis may influence normal and pathological behaviors.

Aging↗

Cell attachment and neurite stability in NG108-15 cells: effects of 5'-deoxy, 5'-methyl thioadenosine (MTA) compared with laminin, kinase inhibitor H-7, and Mn2+ ions.

Methylation inhibitors such as 5'-deoxy, 5'-methyl thioadenosine (MTA) have been shown to exert an intriguing spectrum of effects upon neural cells: inhibiting responses to nerve growth factor in PC12 cells; stimulating outgrowth of rapid-onset neurites in NG108-15 cells; inhibiting the resorption and remodelling of these rapid-onset neurites; and inducing fibroblasts to extend long, multipolar, branched processes. To learn whether the apparently diverse effects of these agents might reflect some common underlying cellular sites of action, we examined simpler, short-term effects of MTA upon cell attachment and stability of rapid-onset neurites in NG108-15 cells, and compared the effects with those produced by the kinase inhibitor H-7, substratum-bound laminin, or Mn2+ ions. MTA was shown to selectively enhance the response of cells and their neurites in attaching to their substrata, without inducing other 'adhesive' responses such as cell spreading or motility. The data suggest that MTA activates or increases the effectiveness of 'attachment receptors', and that this at least partially explains its neurite-promoting effects. While it is still premature to propose a common mechanism of action for MTA and related agents, all of their known effects thus appear to involve modulating responses generated at cell-surface receptors. A further clue is that kinase C activity appears to be critical, since cells pretreated with phorbol esters for 24 h (which down-regulated levels of kinase C) selectively failed to extend neurites in response to MTA, but responded normally to laminin and Mn2+ ions.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

The rapid diagnosis of urinary tract infection: a side-room method.

A controlled trial of a rapid method for microscopic examination of the urine for organisms is reported. The method achieved results as accurate as those of semi-quantitative culture, at minimal cost. It is easy enough to be learned by medically untrained staff, and results are available within 10 minutes. This rapid availability of results makes it possible to prescribe more appropriately at the initial consultation.

Bacteriological Techniques↗

Brain-derived neurotrophic factor rapidly enhances synaptic transmission in hippocampal neurons via postsynaptic tyrosine kinase receptors.

Although neurotrophins are primarily associated with long-term effects on neuronal survival and differentiation, recent studies have shown that acute changes in synaptic transmission can also be produced. In the hippocampus, an area critically involved in learning and memory, we have found that brain-derived neurotrophic factor (BDNF) rapidly enhanced synaptic efficacy through a previously unreported mechanism--increased postsynaptic responsiveness via a phosphorylation-dependent pathway. Within minutes of BDNF application to cultured hippocampal neurons, spontaneous firing rate was dramatically increased, as were the frequency and amplitude of excitatory postsynaptic currents. The increased frequency of postsynaptic currents resulted from the change in presynaptic firing. However, the increased amplitude was postsynaptic in origin because it was selectively blocked by intracellular injection of the tyrosine kinase receptor (Ntrk2/TrkB) inhibitor K-252a and potentiated by injection of the phosphatase inhibitor okadaic acid. These results suggest a role for BDNF in the modulation of synaptic transmission in the hippocampus.

Animals↗

Cortico-hippocampal interaction and adaptive stimulus representation: a neurocomputational theory of associative learning and memory.

Computational models of the hippocampal region link psychological theories of associative learning with their underlying physiological and anatomical substrates. Our approach to theory development began with a broad description of the computations that depend on the hippocampal region in classical conditioning (Gluck and Myers, 1993 and Gluck and Myers, 2001). In this initial model, the hippocampal region was treated as an Information-processing system that transformed stimulus representations, compressing (making more similar) representations of inputs that co-occur or are otherwise redundant, while differentiating (or making less similar) representations of inputs that predict different future events. This model led to novel predictions for the behavioral consequences of hippocampal-region lesions in rodents and of brain damage in humans who have amnesia or are in the earliest stages of Alzheimer's disease. Many of these predictions have, since been confirmed by our lab and others. Functional brain imaging studies have provided further supporting evidence. In more recent computational modeling, we have shown how some aspects of this proposed information-processing function could emerge from known anatomical and physiological characteristics of the hippocampal region, including the entorhinal cortex and the septo-hippocampal cholinergic system. The modeling to date lays the groundwork for future directions that increase the depth of detail of the biological modeling, as well as the breadth of behavioral phenomena addressed. In particular, we are working now to reconcile these kinds of incremental associative learning models with other models of the hippocampal region that account for the rapid formation of declarative memories.

Animals↗

Isolation rearing-induced facilitation of Pavlovian learning: abolition by postsession intra-amygdala nafadotride.

It has been shown previously in this laboratory that rats reared in social isolation acquire a Pavlovian-conditioned approach task much more rapidly than their respective controls. This study assessed the involvement specifically of the mesoamygdaloid dopamine pathway in this facilitated learning of isolates. Thus, animals were required to associate arbitrary stimuli with a pulsed light stimulus (unconditioned stimulus, US). The US, while without biological significance, was nevertheless capable of eliciting an intrinsic and sustained alerting response. Procedures ensured that the arbitrary stimuli (tone or clicker) did not elicit a response in the first instance, and were presented either paired (CS+) or unpaired (CS-) with the US. Isolates and socially reared controls received intra-amygdala infusions of the D3 dopamine receptor antagonist, L-nafadotride, or vehicle immediately following the end of each training session. The conditioned response increased over sessions in both groups of vehicle-infused rats during presentations of the CS+ stimulus, but not CS-, and isolates acquired this association more rapidly than controls. However, acquisition of this association was abolished by postsession intra-amygdala L-nafadotride. Responding to the US was largely unaffected by drug or rearing conditions. Hence, these data provide strong evidence for the specific involvement of the mesoamygdaloid dopamine projection in the facilitation of associative learning by isolation rearing.

Acoustic Stimulation↗

DNA testing for fragile X syndrome in 255 males from special schools in Singapore.

INTRODUCTION: Fragile X syndrome, the most common cause of inherited mental retardation, results from unstable expansion of a trinucleotide (CGG)n repeat in the FMR1 gene. Phenotypic expression is variable making clinical diagnosis difficult, while diagnosis by Southern blotting is relatively expensive and labour intensive. The prevalence in Singapore has not been studied. MATERIALS AND METHODS: We developed a rapid screening test using a PCR analysis. We studied 255 males with unexplained cause for learning difficulties from 8 special schools. A clinical scoring system based on characteristic features described was devised. RESULTS: PCR analysis showed absence of the band for the normal allele in 11 samples, 6 of which were confirmed by Southern blotting to be positive for FMR1 expansion, giving a 2% false-positive rate with PCR. Sensitivity of the PCR test was evaluated by performing Southern blotting in all PCR-normal samples; all of which were confirmed to be normal. This PCR test was shown to be highly reproducible. Clinical criteria were not predictive. CONCLUSIONS: Six (2.4%) new cases of fragile X syndrome were detected. There is a need to incorporate fragile X testing in routine screening of patients with developmental delay and learning difficulties. The use of PCR could eliminate the need for Southern blotting in up to 95% of cases. PCR analysis provides a simple, reliable and rapid tool for screening.

Adolescent↗

Development of sex-trait stereotypes among young children in the United Staes, England, and Ireland.

The Sex Stereotype Measure II (SSM II), a 32-item revision of the Williams, Bennett, and Best Sex Stereotype Measure, was developed to assess children's knowledge of conventional, sex-trait stereotypes defined by American university students. The procedure employed brief stories and human figure silhouettes which were individually administered to 5- and 8-year-old children in the United States, England, and Ireland and group administered to 11-year-olds in the United States. In the United States, knowledge of sex-trait stereotypes was found to develop in a linear fashion between the ages of 5 and 11, with more male traits than female traits being known at each age level. Cross-nationally, there was a high degree of similarity in the nature of the sex stereotypes being learned by the children in the 3 countries, although the rate of learning appeared slower among the Irish children. In all countries there was a clear progression in sex-stereotype learning from age 5 to age 8. English boys had greater knowledge of stereotypes than English girls, but this was not true in Ireland and the United States. Generally, knowledge of male stereotype traits appeared to develop earlier while knowledge of the female traits increased more rapidly between ages 5 and 8. The similarity in sex-stereotype learning in the 3 countries is discussed, and studies in progress in other countries of greater cultural diversity are noted.

Behavior↗

Repeated acquisition and performance chamber for mice: a paradigm for assessment of spatial learning and memory.

Molecular genetic manipulation of the mouse offers the possibility of elucidating the function of individual gene products in neural systems underlying learning and memory. Many extant learning paradigms for mice rely on negative reinforcement, involve simple problems that are relatively rapidly acquired and thus preclude time-course assessment, and may impose the need to undertake additional experiments to determine the extent to which noncognitive behaviors influence the measures of learning. To overcome such limitations, a multiple schedule of repeated acquisition and performance was behaviorally engineered to assess learning vs rote performance within-behavioral test session and within-subject utilizing an apparatus modified from the rat (the repeated acquisition and performance chamber; RAPC). The multiple schedule required mice to learn a new sequence of door openings leading to saccharin availability in the learning component during each session, while the sequence of door openings for the performance component remained constant across sessions. The learning and performance components alternated over the course of each test session, with different auditory stimuli signaling which component was currently in effect. To validate this paradigm, learning vs performance was evaluated in two inbred strains of mice: C57BL/6J and 129/SvJ. The hippocampal dependence of this measure was examined in lesioned C57BL/6J mice. Both strains exhibited longer latencies and higher errors in the learning compared to the performance component and evidenced declines in both measures across the trials of each session, consistent with an acquisition phenomenon. These same measures showed little or no evidence of change in the performance component. Whereas three trials per session were utilized with C57BL/65 mice in each component, behavior of 129/SvJ mice could only be sustained for two trials per component per session, demonstrating differences in testing capabilities between these two strains under these experimental conditions and thus precluding the ability to make systematic strain comparisons of learning capabilities. Hippocampal lesions in C57BL/6J mice resulted in substantially longer latencies and increased errors in the learning but not the performance component, demonstrating the importance of this region to spatial learning as measured in the RAPC. In aggregate, this positive reinforcement-based operant paradigm to evaluate murine spatial learning detects strain differences and hippocampal dependence and permits explicit differentiation of the impact of noncognitive contributions to learning measures on a within-subject, within-session basis.

Animals↗

Application of rapid prototyping to operative dentistry curriculum.

Computers are becoming an integral part of dental education and dental practice. Rapid prototyping is a technique for the production of solid objects from computer models. The variety of rapid prototyping devices and materials that can be processed is increasing all the time. In this article, the authors present a discriminative learning device and associated exercises for developing visual recognition skills and examine the potential for the application of rapid prototyping to the operative dentistry curriculum. Other rapid prototyping technologies as applied in dentistry are also discussed.

Computer Simulation↗

Multiple-unit activity of the prefrontal cortex and mediodorsal thalamic nucleus during reversal learning of discriminative avoidance behavior in rabbits.

Multiple-unit activity of the prefrontal cortex (PFC) and the mediodorsal (MD) thalamic nucleus was recorded during reversal training following differential conditioning of a locomotory (wheel rotation) avoidance response in rabbits. The positive and negative conditional stimuli (CS+ and CS-) were pure tones and the unconditional stimulus (UCS) was footshock. A major objective was to compare the activity in the PFC and MD nucleus with that in the neighboring cingulate cortical and anteroventral (AV) thalamic system, studied previously. During the first session of reversal training the rostral-sulcal subfield of the PFC manifested significant discriminative activity appropriate to the original habit, i.e., a greater discharge to the original CS+ than to the original CS-. The difference between the CS+ and CS- elicited discharges diminished as reversal learning progressed, but discriminative activity appropriate to the reversal problem did not develop. The medial subdivision of the MD nucleus which is interconnected reciprocally with the rostral-sulcal PFC subfield did not manifest discriminative activity during reversal training (nor had it done so during original learning). The caudal subfield of the PFC (which had shown rapidly developing acquisition of the discriminative discharges followed by diminution of the discriminative discharges during original training) manifested an original discriminative effect in the initial session of reversal training followed by the reverse discriminative discharge in the criterial session. The lateral subdivision of the MD nucleus which is interconnected reciprocally with the caudal PFC subfield, also manifested the original discriminative effect in the initial session of reversal training, followed by the reverse discriminative effect during the subsequent (precriterial and criterial) sessions. Thus, as in the AV nucleus, the lateral MD subdivision showed earlier and more robust development of discriminative activity appropriate to the reversal problem, than its cortical counterpart. The present results also suggested that cerebral cortical areas such as the caudal PFC, which transfer discriminative activity to their respective thalamic nuclei during discriminative acquisition, are subsequently more likely to manifest the reverse discriminative activity, than are cortical areas such as the rostral-sulcal subfields of the PFC, which do not transfer their discriminative activity.

Animals↗

Learning and neural plasticity in visual object recognition.

The capability of the adult primate visual system for rapid and accurate recognition of targets in cluttered, natural scenes far surpasses the abilities of state-of-the-art artificial vision systems. Understanding this capability remains a fundamental challenge in visual neuroscience. Recent experimental evidence suggests that adaptive coding strategies facilitated by underlying neural plasticity enable the adult brain to learn from visual experience and shape its ability to integrate and recognize coherent visual objects.

Animals↗

Can family members of high-risk cardiac patients learn cardiopulmonary resuscitation?

The immediate delivery of bystander-administered cardiopulmonary resuscitation (CPR), coupled with the rapid delivery of advanced cardiac life support, can significantly reduce mortality from out-of-hospital cardiac arrest. Because the majority of sudden cardiac deaths occur in the victim's home with family members present, family members of cardiac patients at high risk for sudden death are the logical focus of CPR training. However, previous research has shown that only a small minority of family members of cardiac patients actually learn CPR and that health care professionals have failed to recommend CPR training in this population, in part due to concerns about their ability to learn CPR. The purpose of this study was to describe learning capabilities in this population and to identify characteristics of unsuccessful learners. To this end, we taught CPR to 83 family members of cardiac patients who were at risk for sudden cardiac death. Subjects had no CPR training within the past two years. Eighty-one percent of the subjects successfully learned CPR. Of the demographic and psychological characteristics examined, only gender, age, and depression were significant in explaining differences in CPR skills attainment ability. The elderly, the depressed, and males were more likely to be unsuccessful in demonstrating adequate CPR skills. Our results suggest that the majority of family members of cardiac patients can learn CPR successfully. Specific training strategies may need to be developed and tested to enhance CPR training in those family members of cardiac patients predicted to have difficulty learning CPR.

Adult↗

Learning style preferences of community mental health professionals.

Programs of continuing education in mental health are increasing at a rapid pace. This study examines-selected personal and occupational characteristics of enrollees in one such program and classifies the nature of enrollee motivation for participating in specialized programs of community mental health training. The learning-style preferences of these highly experienced professionals are also explored and recommendations are made concering the design of similar educational programs under development elsewhere.

Adult↗

The evaluation of multimedia learning packages in the education of health professionals: experience of a musculoskeletal examination package.

The last 20 years have seen rapid technological developments within the field of information technology. The internet, sophisticated software packages and increased accessibility to computers have all opened opportunities for educators. Against this background, increasing numbers of multimedia learning packages are available to the health professional. In this paper, Pirashanthie Vivekananda-Schmidt, Andrew Hassell and Monica McLean discuss the methodological issues relating to the evaluation of such multimedia based learning tools, using the example of a specific package, Virtual Rheumatology. They discuss the reasons for the increasing interest in the area of computer-based learning, the available evidence supporting the use of such tools in education, and issues about the design and production of this CD. They then discuss the evaluation of the package to illustrate the considerable methodological difficulties in the research and evaluation of Computer Assisted Learning (CAL) packages generally.

Attitude of Health Personnel↗

The ascending neuromodulatory systems in learning by reinforcement: comparing computational conjectures with experimental findings.

A central problem in cognitive neuroscience is how animals can manage to rapidly master complex sensorimotor tasks when the only sensory feedback they use to improve their performance is a simple reinforcing stimulus. Neural network theorists have constructed algorithms for reinforcement learning that can be used to solve a variety of biological problems and do not violate basic neurophysiological principles, in contrast to the back-propagation algorithm. A key assumption in these models is the existence of a reinforcement signal, which would be diffusively broadcast throughout one or several brain areas engaged in learning. This signal is further assumed to mediate up- and downward changes in synaptic efficacy by acting as a multiplicative factor in learning rules. The biological plausibility of these algorithms has been defended by the conjecture that the neuromodulators noradrenaline, acetylcholine or dopamine may form the neurochemical substrate of reinforcement signals. In this commentary, the predictions raised by this hypothesis are compared to anatomical, electrophysiological and behavioural findings. The experimental evidence does not support, and often argues against, a general reinforcement-encoding function of these neuromodulatory systems. Nevertheless, the broader concept of evaluative signalling between brain structures implied in learning appears to be reasonable and the available algorithms may open new avenues for constructing more realistic network architectures.

Adaptation, Psychological↗

Skin cancer prevention: the problem, responses, and lessons learned.

Skin cancer is one of the most common forms of cancer and has rapidly increased during the past three decades in the United States. More than 1 million new cases of skin cancer are estimated to be diagnosed in the United States each year. The National Skin Cancer Prevention Education Program (NSCPEP) was launched by the Centers for Disease Control and Prevention (CDC) in 1994 as a national effort to address the Healthy People 2000 objectives for skin cancer prevention. The NSCPEP is a comprehensive, multidimensional public health approach that includes (1) primary prevention interventions; (2) coalition and partnership development; (3) health communications and education; and (4) surveillance, research, and evaluation. In 1994, through support from the CDC, state health departments in Arizona, California, Georgia, Hawaii, and Massachusetts initiated primary prevention intervention projects to conduct and evaluate skin cancer prevention education. This article discusses the comprehensive, multidimensional public health approach highlighting examples from the state demonstration projects.

Adolescent↗

Development and cancer: lessons learned in the pancreas.

Cancer progression and organ development are similar phenomena. Both involve rapid bursts of proliferation, angiogenesis, tissue remodeling, and cell migration. Therefore, it is not surprising that both processes utilize similar signaling machinery. In fact, many recent studies have suggested that cancer is a disease triggered by the erroneous re-activation of signaling pathways that are typically downregulated after the completion of embryonic development. This link between embryonic development and cancer is particularly exciting because it suggests that we might be able to exploit the knowledge gained in studies of Developmental Biology to obtain novel insights into tumor biology. Our evolving understanding of pancreatic adenocarcinoma is an excellent example of this relationship between development and cancer. Here we discuss recent studies have indicated important roles for two major developmental signaling pathways in pancreatic cancer: Notch and Hedgehog (Hh).

Adenocarcinoma↗