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Neural correlates of internal-model loading.

Skilled object manipulation requires knowledge, or internal models, of object dynamics relating applied force to motion , and our ability to handle myriad objects indicates that the brain maintains multiple models . Recent behavioral studies have shown that once learned, an internal model of an object with novel dynamics can be rapidly recruited and derecruited as the object is grasped and released . We used event-related fMRI to investigate neural activity linked to grasping an object with recently learned dynamics in preparation for moving it after a delay. Subjects also performed two control tasks in which they either moved without the object in hand or applied isometric forces to the object. In all trials, subjects received a cue indicating which task to perform in response to a go signal delivered 5-10 s later. We examined BOLD responses during the interval between the cue and go and assessed the conjunction of the two contrasts formed by comparing the primary task to each control. The analysis revealed significant activity in the ipsilateral cerebellum and the contralateral and supplementary motor areas. We propose that these regions are involved in internal-model recruitment in preparation for movement execution.

Adult↗

HIV-1 protein gp120 rapidly impairs memory in chicks by interrupting the glutamate-glutamine cycle.

Learning and memory impairments are frequently observed in patients suffering from AIDS Dementia Complex (ADC). These effects have been linked to the presence of gp120, an HIV viral coat glycoprotein. The present study investigated the possibility that gp120 prevents the uptake of extracellular glutamate by astrocytes, leading to an interruption of the glutamate-glutamine cycle and a subsequent impairment of memory. Ten microliters of 10nM gp120 was bilaterally injected into the region of the intermediate medial mesopallium of day-old chicks at various times before, or after, training using a single-trial passive avoidance task. Gp120 was found to significantly impair memory retention when injected 10-40 min after training. Memory impairments were evident within 5 min of gp120 administration and remained evident 24h later. Further, the amnestic effect of gp120 could be overcome with glutamine or with precursors of glutamate synthesis, but only weakly by glutamate. These results support the conclusion that the amnestic effect of gp120 is due to an impaired uptake of glutamate by astrocytes and a subsequent interruption of glutamine supply to neurones. The data indicate that the glutamate-glutamine cycle may be a useful therapeutic target in the treatment of ADC.

Amnesia↗

Prophages and bacterial genomics: what have we learned so far?

Bacterial genome nucleotide sequences are being completed at a rapid and increasing rate. Integrated virus genomes (prophages) are common in such genomes. Fifty-one of the 82 such genomes published to date carry prophages, and these contain 230 recognizable putative prophages. Prophages can constitute as much as 10-20% of a bacterium's genome and are major contributors to differences between individuals within species. Many of these prophages appear to be defective and are in a state of mutational decay. Prophages, including defective ones, can contribute important biological properties to their bacterial hosts. Therefore, if we are to comprehend bacterial genomes fully, it is essential that we are able to recognize accurately and understand their prophages from nucleotide sequence analysis. Analysis of the evolution of prophages can shed light on the evolution of both bacteriophages and their hosts. Comparison of the Rac prophages in the sequenced genomes of three Escherichia coli strains and the Pnm prophages in two Neisseria meningitidis strains suggests that some prophages can lie in residence for very long times, perhaps millions of years, and that recombination events have occurred between related prophages that reside at different locations in a bacterium's genome. In addition, many genes in defective prophages remain functional, so a significant portion of the temperate bacteriophage gene pool resides in prophages.

Base Sequence↗

A professional development model: rewarding excellence in nursing practice.

Change continues to be the only constant in health care. The array of rapid and complex changes in the provision of health care services is dramatically affecting the development needs of professional nursing staff. The model presented describes a theoretical framework designed to support the philosophy of both continuous learning and professional development of nurses and also provides a structure for systematic implementation of objectives, content, and learning activities. Linking of professional development models with reward systems is rapidly becoming a successful strategy for organizations in achieving cost-quality outcomes. This model provides a map for staff and management to support, recognize, and reward professional development.

Clinical Competence↗

Classical conditioning rapidly induces specific changes in frequency receptive fields of single neurons in secondary and ventral ectosylvian auditory cortical fields.

To determine if learning-induced changes in the response of auditory cortical neurons to a conditioned stimulus (CS) reflect general changes in cellular excitability or alterations in signal processing that are specific to that stimulus, we determined frequency receptive fields (FRFs) of single neurons in secondary and ventral ectosylvian auditory fields of the cat during classical conditioning. Associative changes in FRFs of most cells were specific to the frequency of the CS, established rapidly and reversed by extinction. Thus, learning causes specific changes in cortical processing of sounds whose significance is acquired.

Animals↗

Language comprehension in language-learning impaired children improved with acoustically modified speech.

A speech processing algorithm was developed to create more salient versions of the rapidly changing elements in the acoustic waveform of speech that have been shown to be deficiently processed by language-learning impaired (LLI) children. LLI children received extensive daily training, over a 4-week period, with listening exercises in which all speech was translated into this synthetic form. They also received daily training with computer "games" designed to adaptively drive improvements in temporal processing thresholds. Significant improvements in speech discrimination and language comprehension abilities were demonstrated in two independent groups of LLI children.

Algorithms↗

Ontogeny of active avoidance in the rat: learning and memory.

Ontogenetic development of active avoidance learning, extinction and retention was studied in rats. The learning of a 1-way active avoidance was most rapid between Weeks 4 and 6, although some slight gender-related differences were evident. No such unambiguous development was detected in forced extinction. The 24-hr retention of avoidance peaked at the age of 4 weeks whereas 1-month retention was best in animals trained at the age of 8 weeks. The retrieval of memory trace also had best values at these ages. Retention of forced extinction was found to peak in 6-week animals. The existence of developmental "critical periods" must be considered cautiously as various functions have different time courses depending upon the chosen parameters in assessment.

Animals↗

Young children's acquisition of wh-questions: the role of structured input.

Two-year-olds learn language quickly but how they exploit adult input remains obscure. Twenty-nine children aged 2;6 to 3;2, divided into three treatment groups, participated in an intervention experiment consisting of four sessions 1 week apart. Pre- and post-intervention sessions were identical for all children: children heard a wh-question and attempted to repeat it; a 'talking bear' answered. That same format was used for the two intervention sessions for children in a quasicontrol condition (Group QC). Children receiving modelling (Group M) heard a question twice before repeating it; those receiving implicit correction (Group IC) heard a question, attempted to repeat it, and heard it again. All groups improved in supplying and inverting an auxiliary for target questions with trained auxiliaries. Only experimental children generalized to auxiliaries on which they had not been trained. Very little input, if concentrated but varied, and presented so that the child attends to it and attempts to parse it, is sufficient for the rapid extraction and generalization of syntactic regularities. Children can learn even more efficiently than has been thought.

Child Language↗

Impairments of learning and memory following intracerebroventricular administration of AF64A in rats.

Three types of learning and memory tests (Morris water maze, active and passive avoidance) were performed in rats following intracerebroventricular infusion of ethylcholine aziridium (AF64A). In Morris water maze, AF64A-treated rats showed the delayed latencies to find the platform from 6th day after the infusion. In pretrained rats, AF64A caused the significant delay of latency at 7th day, but not 8th day. In the active avoidance for the pre-trained rats, the escape latency was significantly delayed in AF64A-treatment. The percentages of avoidance in AF64A-treated rats were less increased than those in the control. Especially, the percentage of no response in the AF64A-treated rats was markedly increased in the first half trials. In the passive avoidance, AF64A-treated rats shortened the latency 1.5 h after the electronic shock, but not 24 h. AF64A also caused the pretrained rats to shorten the latency 7th day after the infusion, but not 8th day. These results indicate that AF64A might impair the learning and memory. However, these results indicate that the disturbed memory by AF64A might rapidly recover after the first retrain. Furthermore, these results suggest that AF64A may be a useful agent for the animal model of learning for spatial cognition.

Animals↗

Sexual approach conditioning: unconditioned stimulus factors.

Unconditioned stimulus (US) factors were investigated in a Pavlovian sexual conditioning paradigm with male Japanese quail (Coturnix coturnix japonica). Copulation with a female quail was more effective than exposure to a female without copulation, but the latter also produced conditioned responding (Experiment 1). The greater effectiveness of copulatory opportunity as a US was probably not due to nonassociative effects of copulation (Experiment 2). Visual cues of the female, as presented on a taxidermic model, were not effective unless the subjects had prior sexual experience that increased their response to the model (Experiments 3a and 3b). Successful conditioning with noncopulatory female exposure is significant because it allows for sexual learning to occur in a broader range of circumstances than does conditioning with copulation and because it permits conducting multiple trials per day because males do not become satiated as rapidly.

Animals↗

Web-based learning in professional development: experiences of Finnish nurse managers.

AIM: The aim of this article is to describe the nurse managers' expectations, attitudes and experiences on web-based learning before and after participation in a web-based course. BACKGROUND: Information technology has rapidly become more common in health care settings. However, little is known about nurse managers' experiences on web-based learning, although they have a crucial role in promoting the professional development of their staff. METHODS: Diagnostic assignments (n = 18) written before and interviews (n = 8) taken after the web-based education. The data were analysed by inductive content analysis. RESULTS: Nurse managers found web-based education to be a suitable and modern method of learning. On the basis of their experience they found multiple ways to utilize web-based learning environments in health care. Information technology skills, equipment, support and time were considered essential in web-based learning. Additionally, they found that their own experience might lead to more widespread implementation of web-based learning in health care settings. CONCLUSIONS: Information technology skills of nurse managers and staff need to be developed in order to use information technology effectively. In order to learn in a web-based environment, everyone needs the opportunity and access to required resources. Additionally, nurse managers' own experiences are important to promote wider utilization of web-based learning.

Education, Nursing, Continuing↗

Evolution in microcosm: the rapid somatic diversification of lymphocytes.

The characteristic task of the immune system is learning to respond specificially to entirely novel antigens. How it may do this is discussed under 6 headings. 1. -- Vertebrate and invertebrate immune strategies are contrasted. Whereas among invertebrates whole individuals appear to be selected for their immunological fitness, vertebrates have developed an internal population of lymphocytes among which variants arise and are selectively stimulated by antigen to give a response which protects the "host". 2. -- The genetic mechanism underlying this variation of lymphocytes is of great interest, but its discovery will not, given present ignorance of eukarote DNA, answer those questions about variation at the phenotypic level which are vital to the rest of immunology: e.g. when, how fast, and under what conditions do variantes arise? 3. -- A great deal of indirect evidence suggests that the production of entirely new variant lymphocytes occurs throughout life, particularly after antigenic stimulation. 4. -- Experimental approaches are discussed which might provide direct evidence for or against the idea of rapid variation among stimulated lymphocytes. The method used was based on detecting the cross-reactive specificity of antibody produced by single cells. 5. -- Evidence obtained with this technique is briefly described. There were two main kinds of experiment. In the first, rapid variation (at the rate of about one variation event per 30 divisions) was demonstrated within single clones of proliferating antibody-forming cells. In the second group of experiments, it was shown that certain uncommon antibody-forming cell specificities present at the peak of a primary response were entirely absent at earlier stages. 6. -- A new immunological paradigm may emerge from work on the generation of diversity and on active control of response. There may be relatively few types of lymphocytes with germ-line-coded receptors. These are stimulated by environmental antigens and mitogens, and perhaps by self stimulated by environmental antigens and mitogens, and perhaps by self antigens. Extensive proliferation and variation occurs, which in turn elicits suppressor reactions directed against antigen or against idiotypes of responding clones. The immune repertoire of the adult vertebrate is a product of the evolution of its lymphocytes under the competing pressures of antigenic stimulation and active suppression.

Aging↗

Linear relationship between the maintenance of hippocampal long-term potentiation and retention of an associative memory.

The hypothesis that the maintenance or decay of an associative memory trace after an extended retention interval is a function of the residual strength of the synapses originally strengthened during learning was examined in a classical conditioning paradigm in which high-frequency stimulation of a hippocampal input--the medial perforant path--served as a conditioned stimulus. Rats received perforant path stimulus-foot shock pairings while engaged in a previously acquired food-motivated lever-pressing task. Conditioned suppression of lever pressing was the behavioral measure of learning and retention of the association. Stimulus trains to the perforant path at an intensity above the threshold for eliciting a population spike induced long-term potentiation of synaptic transmission in the dentate gyrus. Synaptic potentials recorded extracellularly in the dentate gyrus were subsequently monitored for 31 days to examine quantitatively the decay of synaptic potentiation, a period after which retention of the learned association was assessed. All rats learned the association to a similar extent and displayed equivalent amounts of long-term potentiation by the end of conditioning. A slowly decaying function of synaptic potentiation was observed in remembering rats, i.e., rats with high retention performance after the 31-day learning-to-retention interval, while forgetting was associated with a rapid decay of long-term potentiation. Behavioral performance at the long-term memory test was linearly correlated with the amplitude of long-term potentiation maintained just prior to the retention test. The results favor the hypothesis that long-term associative memory depends, at least in part, on the maintenance of elevated synaptic strengths in the pathway activated during learning and suggest a role for the lasting component of long-term potentiation in the maintenance of memory.

Animals↗

Timing is essential for rapid effects of corticosterone on synaptic potentiation in the mouse hippocampus.

Stress facilitates memory formation, but only when the stressor is closely linked to the learning context. These effects are, at least in part, mediated by corticosteroid hormones. Here we demonstrate that corticosterone rapidly facilitates synaptic potentiation in the mouse hippocampal CA1 area when high levels of the hormone and high-frequency stimulation coincide in time, but not when corticosterone is given either before or after repetitive stimulation. This effect could not be blocked by antagonists of the mineralocorticoid receptor and glucocorticoid receptor (spironolactone and RU 38486, respectively). These data provide a biological substrate for the important behavioral observation that stress and corticosteroid hormones can facilitate learning and memory processes.

Analysis of Variance↗

Activation of the phasic pontine-wave generator enhances improvement of learning performance: a mechanism for sleep-dependent plasticity.

The aim of this study was to test the hypothesis that supplementary activation of the phasic pontine wave (P-wave) generator during rapid eye movement (REM) sleep enhances consolidation and integration of memories, resulting in improved learning. To test this hypothesis, two groups of rats were trained on a two-way active avoidance learning task in the morning. Immediately after training, one group of rats received a carbachol microinjection into the P-wave generator and the other group was microinjected with control saline into the same target area. After training trials and microinjections, rats were allowed a 6-h period of undisturbed sleep in the polygraphic recording chamber. At the end of 6 h of undisturbed sleep-wake recordings, rats were retested in a session of avoidance learning trials. After learning trials, the total percentage of time spent in REM sleep was significantly increased in both saline (15.36%)- and carbachol (17.70%)-microinjected rats. After learning trials, REM sleep P-wave density was significantly greater throughout the 6-h period of recordings in carbachol treated rats than in the saline treated rats. In the retrial session, the improvement in learning task performance was 22.75% higher in the carbachol-microinjected rats than in the saline-microinjected rats. These findings show that the consolidation and integration of memories create a homeostatic demand for P-waves. In addition, these findings provide experimental evidence, for the first time, that activation of the P-wave generator may enhance consolidation and integration of memories, resulting in improved performance on a recently learned task.

Animals↗

Physiological properties of vestibular primary afferents that mediate motor learning and normal performance of the vestibulo-ocular reflex in monkeys.

We have used electrical stimulation of the vestibular apparatus to reveal parallels between the physiological responses of the vestibular afferents activated at different currents and the properties of the evoked eye movements before and after magnifying spectacles had been used to cause motor learning in the vestibulo-ocular reflex (VOR). Stimulation with the lowest currents caused little or no eye motion, but activated all the afferents with irregular spontaneous discharge, low sensitivities to head velocity, and highly phasic responses during rapid head turns. Stimulation with moderate currents caused substantial eye motion that was weakly affected by motor learning; these currents activated afferents with a wide range of physiological properties, including many that had intermediate discharge regularity, high sensitivity to head velocity, and clear phasic responses during rapid head turns. Stimulation at still higher currents caused still larger eye movements that were strongly altered by motor learning; these currents activated primarily afferents that had regular spontaneous discharge, lower sensitivities to head velocity, and tonic responses during rapid head turns. Stimulation at the highest currents did not cause any further increment in the amplitude of the evoked eye movement, but activated the afferents with the most regular spontaneous discharge and the lowest sensitivities to head velocity. The data imply that the VOR pathways receive substantial vestibular inputs from afferents with a middle range of thresholds for electrical stimulation. These afferents have a wide range of physiological properties, including a large group that shows substantial phasic responses during rapid head turns. The data also suggest that only a subset of these afferents, primarily those with more regular spontaneous discharge, project into the VOR pathways that are modified in association with motor learning.

Afferent Pathways↗

Substantia nigra pars compacta is critical to both the acquisition and expression of learned orienting of rats.

Novel events produce characteristic orienting responses (ORs), which typically habituate rapidly with repeated stimulus presentation. However, they may re-emerge if those stimuli become predictors of biologically significant events. This acquisition of conditioned ORs may reflect a broader range of enhancements in top-down attentional processing of cues that predict important consequences. Previous research from this laboratory showed that a neural circuit that includes the amygdala central nucleus (CeA), substantia nigra pars compacta (SNc) and dorsolateral striatum (DLS) is essential for the learning and expression of one example of conditioned orienting, the rearing of rats to visual stimuli paired with food. Other studies showed that the CeA is critical to the acquisition of these conditioned ORs, but not their expression, and that normal DLS function is required for the expression of previously acquired conditioned ORs, but not for learning itself. The experiments reported here considered the roles of the SNc in conditioned orienting by examining the effects of transient inactivation of the SNc during the acquisition of new associations and during the expression of previous learning. SNc function was critical to both the acquisition and expression of conditioned ORs but not to the display of unconditioned ORs or the learning and expression of conditioned responses directed to the food source. Together with our previous findings, these results suggest that the SNc is trained by the CeA during learning and maintains acquired information so that it may modulate DLS sensory-motor function at the time of action.

Animals↗