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PubMed2004

Targeted introduction of V642I mutation in amyloid precursor protein gene causes functional abnormality resembling early stage of Alzheimer's disease in aged mice.

While the exact aetiology of Alzheimer's disease (AD) is unknown, distinct genetic mutations have been identified for the rare cases of familial AD (FAD). V642I mutation in amyloid precursor protein (APP) co-segregates with FAD with perfect penetration, and the clinicopathological characteristics of patients with this mutation resemble that of sporadic AD. To examine the pathogenic process of this FAD-linked trait in vivo, we produced a mouse with the corresponding point mutation in the APP gene using homologous recombination and Cre-loxP site-specific recombination ('knock-in' technique). Mice with the heterozygous V642I-APP allele most precisely reflected the genotype of humans bearing this mutation. For the observation period of 2.5 years the mutants stayed apparently indistinguishable from the wild-type littermates. However, behavioural analysis revealed significantly deteriorated long-term memory in mutants when examined for the retention of spatial attention. Interestingly, acquisition of spatial memory was slightly affected but short-term working memory was not deteriorated at all. Histological examination was negative for formation of neuritic plaques or neurofibrillary tangles, whereas the relative amount of longer form of beta-amyloid species A beta 42(43) was significantly increased against that of the shorter form (A beta 40) in the mutant brain homogenates. We conclude that a V642I-APP mutant allele in aged mice confers functional components, but not organic components, of the AD-related phenotype that are observed in the early stage of AD. This V642I-APP knock-in mutant line may serve as a model to study the early pathogenic processes of AD in vivo and to develop therapeutics for this stage.

Age Factors↗
PubMed1992

A comparison of light intensity preferences for an oviposition site in parthenogenetic and bisexual strains of Drosophila.

On the assumption that the survival of a parthenogenetic strain in nature relies on the strain's ability to compete with the bisexual population, we attempted to discern any diminution of competition between bisexual strains of Drosophila and parthenogenetic strains derived from them on the basis of light intensity preferences in choosing an oviposition site. Four different experiential conditions were imposed on each strain prior to testing for light intensity preferences for an oviposition site. Most light responses are significantly different in each strain for the four experiences. There are also significant differences among the bisexual, unisexual and F1 females of a given strain and between strains. Further experiments were performed to determine light preferences during oviposition when unisexual and bisexual females were in direct competition. In only one comparison were their light preferences significantly different. All strains were unique in their overall behavioral spectra.

Animals↗
PubMed2004

Motion mechanisms in macaque MT.

The macaque middle temporal area (MT) is exquisitely sensitive to visual motion and there is a large amount of evidence that neural activity in MT is tightly correlated with the perception of motion. The mechanisms by which MT neurons achieve their directional selectivity, however, have received considerably less attention. We investigated the motion-energy model as a description of motion mechanisms in macaque MT. We first confirmed one of the predictions of the motion-energy model; macaques-just like humans-perceive a reversed direction of motion when a stimulus reverses contrast with every displacement (reverse-phi). This reversal of perceived direction had a clear correlate in the neural responses of MT cells, which were predictive of the monkey's behavioral decisions. Second, we investigated how multiple motion-energy components are combined. Psychophysical data have been used to argue that motion-energy components representing opposite directions are subtracted from each other. Our data show, however, that the interactions among motion-energy components are more complex. In particular, we found that the influence of a given component on the response to a stimulus consisting of multiple components depends on factors other than the response to that component alone. This suggests that there are subthreshold nonlinear interactions among multiple motion-energy components; these could take place within MT or in earlier stages of the motion network such as V1. We propose a model that captures the complexity of these component interactions by means of a competitive interaction among the components. This provides a better description of the MT responses than the subtractive motion opponency envisaged in the motion-energy model, even when the latter is combined with a gain-control mechanism. The competitive interaction extends the dynamic range of the cells and allows them to provide information on more subtle changes in motion patterns, including changes that are not purely directional.

Animals↗
PubMed2006

Eigenanalysis of selection ratios from animal radio-tracking data.

The development of methods to analyze habitat selection when resources are defined by several categories (e.g., vegetation types) is a topical issue in radio-tracking studies. The White and Garrott statistic, an extension of the widely used test of Neu et al., can be used to determine whether habitat selection is significant. As well, Manly's selection ratio, a particularly useful measure of resource selectivity by resource users, allows detection of the most strongly selected habitat types. However, when both the number of animals and types of habitat are large, the biologist often has to deal with an excessively large number of measures. In this paper we present a new method, the eigenanalysis of selection ratios, that generalizes these two common methods within the framework of eigenanalyses. This method undertakes an additive linear partitioning of the White and Garrott statistic, so that the difference between habitat use and availability is maximized on the first factorial axes. The eigenanalysis of selection ratios is therefore optimal in habitat selection studies. Although we primarily consider the case where the habitat availability is the same for all animals (design II), we also extend this analysis to the case where the habitat availability varies from one animal to another (design III). An application of this method is provided using radio-tracking data collected on 17 squirrels in five habitat types. The results indicate variability in habitat selection, with two groups of animals displaying two patterns of preference. This difference between the two groups is explained by the patch structure of the study area. Because this method is mainly exploratory, and therefore does not rely on any distributional assumption, we recommend its use in studies of habitat selection.

Animals↗
PubMed1993

Determinants of human performance on concurrent schedules.

Six experiments, each with 5 human adults, were conducted to investigate the determinants of human performance on multiple concurrent variable-interval schedules. A two-key procedure was employed in which subjects' key presses produced points exchangeable for money. Variables manipulated across experiments were (a) changeover delay (Experiments 2, 4, and 6), (b) ordinal cues related to scheduled reinforcement frequencies (Experiments 3 and 4), and (c) instructions describing the ordinal relations between schedule-correlated stimuli and scheduled reinforcement frequency (Experiments 5 and 6). The performances of only 13 of the 30 subjects could be described by the generalized matching equation and were within a range of values typical of those reported in the animal literature. Eight subjects showed indifference, 9 undermatched, 7 approximated matching, 3 overmatched, and a further 3 responded exclusively to the richer component of the concurrent schedules. These differing modes of responding were closely related to the different types of performance rules reported by subjects in postexperimental questionnaires. The results are in good agreement with those from studies of human performance on single schedules, suggesting that rule-governed behavior, in interaction with contingencies, may be an important determinant of human choice.

Adolescent↗
PubMed2005

Concurrent second-order schedules: some effects of variations in response number and duration.

To examine the effects on concurrent performance of independent manipulations of response-unit duration and number, 6 hens were exposed to concurrent second-order schedules of reinforcement. Each first-order operant unit required completion of a fixed-ratio schedule within the time specified by a fixed-interval schedule, with one further response completing the fixed-interval schedule. The fixed-ratio and fixed-interval requirements comprising the first-order operant units were systematically and independently varied under three pairs of concurrent variable-interval schedules to produce differences in the first-order response and duration requirements (response and duration differentials). These manipulations produced consistent changes in response, time, and operant-unit biases. A 1:4 response differential biased the time and operant-unit measures towards the smaller fixed ratio, but to a degree less than the imposed response differential. The response-based biases favored the larger fixed ratio. Duration differentials of 4:1 and 8:1 biased the response and operant-unit measures towards the shorter fixed interval, again less than the imposed duration differential, but the time biases remained close to zero. Both sorts of differentials acted to bias operant-unit completions more systematically than the other measures, but undermatching to the differentials occurred. The undermatching appears to have arisen from a pattern of fix and sample (in which visits to the less preferred alternative involved only a single completed operant unit) under combinations of unequal operant-unit requirements and reinforcer rates. The response and time bias measures appeared to arise as by-products of the changes in operant-unit completions.

Animals↗
PubMed1984

Structured experience: a risk-free approach to reality-based learning.

The structured experience facilitated learning in an emotionally charged situation by reducing risk factors and the participants' anxieties. It also facilitated discussing and sharing ideas and feelings. The simple format of the Land of Suria enabled not only health care deliverers or students but also experts to learn at their levels of awareness. The learners were able to transfer the knowledge gained from the structured experience to real-life situations. The writer believes that the structured experience can be utilized as a risk-free method of learning prior to potential anxiety-producing situations (i.e., C.C.U., acute psychiatric crises, transcultural situations, etc.) and that the resulting knowledge can be effectively transferred to anxiety-producing, real-life situations. The structured experience is not open-ended for the students to totally define out of their own experience. It is structured to include content and process which the instructor deems valuable. Specific nursing situations can be designed with outcomes predictable within a given range of behaviors. Many variables determine choices of nurses' behaviors, and the structured experience allows the student to bring past learning to the situation and examine what they did, how they did it, why they did it, and how they feel about it. Because the structured experience is learning that encompasses both the cognitive and affective domain, it has the potential of greater impact upon the learner and a greater potential for transfer and retention.(ABSTRACT TRUNCATED AT 250 WORDS)

Education, Nursing↗
PubMed2001

Odor exposure causes central adaptation and morphological changes in selected olfactory glomeruli in Drosophila.

In an attempt to correlate behavioral and neuronal changes, we examined the structural and functional effects of odor exposure in Drosophila. Young adult flies were exposed to a high concentration of the selected odor, usually benzaldehyde or isoamyl acetate, for 4 d and subsequently tested for their olfactory response to a variety of odorants and concentrations. The behavioral response showed specific adaptation to the exposed odor. By contrast, olfactory transduction, as measured in electroantennograms, remained normal. In vivo volume measurements were performed on olfactory glomeruli, the anatomical and functional units involved in odor processing. Pre-exposed flies exhibited volume reduction of certain glomeruli, in an odor-selective manner. Of a sample of eight glomeruli measured, dorsal medial (DM) 2 and ventral (V) were affected by benzaldehyde exposure, whereas DM6 was affected by isoamyl acetate. Estimation of the number of synapses indicates that volume reduction involves synapse loss that can reach 30% in the V glomerulus of flies adapted to benzaldehyde. Additional features of odorant-induced adaptation, including concentration dependence and perdurance, also show correlation, because both effects are elicited by high odor concentrations and are long-lasting (>1 week). Finally, the dunce mutant fails to develop behavioral adaptation as well as morphological changes in the olfactory glomeruli after exposure. These neural changes thus appear to require the cAMP signaling pathway.

Acetates↗
PubMed1999

Herd behavior in designer genes.

The ability of individuals to choose their children's genes has increased over time and may ultimately culminate in a world involving free market reprogenetic technologies. Reprogenetic technologies combine advances in reproductive biology and genetics to provide humans increased control over their children's genes. This Article offers economic perspectives that are helpful in understanding the possibly unexpected ethical, legal, and social issues at stake in using reprogenetic technologies for trait enhancement selection. The Appendix analyzes two competitive games that might arise in such a biotechnological society. Specifically, the Article focuses on herd behavior, caused by either a popularity contest or positional competition, in the choice of genetic traits. The analytical game-theoretic models in the Appendix can have several equilibrium outcomes in terms of individual reprogenetic technological choices and corresponding beliefs about such choices by others. This multiplicity of potential social outcomes suggests that a society can attain efficiency if the state or some private organization transforms individual parents' beliefs over the choices of other parents regarding their children's traits and, thus, coordinates parental reprogenetic decisions by selecting, as focal, certain beliefs over parents' reprogenetic decisions.

Choice Behavior↗
PubMed1992

[Genetic analysis of various behavioral and physiologic characteristics in hybrids between hypertensive and normotensive rats. Analysis of correlational connections].

Hereditary links between different behavioral and physiological traits were studied in rat strains SHR, WKY and their hybrids F1 and F2 by analysis of correlations in segregating and nonsegregating gene-rations. Genetic correlation of arterial pressure with body mass, intake of KC1 solution and the ability to avoidance learning (directed positively) and with characteristics of exploratory activity (directed negatively) was shown. These traits seemed to be possible genetic markers of arterial hypertension. Genetical correlates of the ability to elaborate active avoidance conditional reaction (arterial pressure and pain sensitivity) testify to relief of active avoidance learning in animals with inherited active-defensive type of behaviour, manifested by predisposition to pressor reactions and by suppressed emotional reactions to pain stimulation. Frequency in intertrial crossings during avoidance training displays positive correlation with characteristics of exploratory behaviour. Positive correlation between different characteristics of exploratory activity was established both in segregating and nonsegregating generations.

Animals↗
PubMed1998

Unraveling dopamine D3 receptor function in response to psychostimulants using a genetic approach.

The dopamine D3 receptor is expressed mostly in the limbic regions of the brain that influence reward-related behaviors, including responses to psychostimulants. However, the lack of ligands with sufficient D3 receptor specificity has hampered our understanding of its possible involvement in mediating psychostimulant actions. To unravel dopamine D3 receptor function and underlying mechanisms in response to psychostimulants, we used a genetic approach and generated D3 receptor gene mutant mice. Our analysis indicates that the D3 mutant mice exhibit enhanced behavioral sensitivity to cocaine, amphetamine and combined injections of D1-and D2-class receptor agonists. By contrast, the combined electrophysiological effects of the same D1-and D2-class agonists on single neurons within the nucleus accumbens were not changed in the D3 mutant mice. We propose that the D3 receptor modulates responses to psychostimulants by inhibiting the cooperative effects of postsynaptic D1-and other D2-class receptors at systems level. The continuous use of the gene targeting approach will provide essential information regarding the molecular and cellular basis of psychostimulant actions and allow the development of new strategies in the prevention and cure of drug abuse.

Amphetamine↗
PubMedDate not supplied

The effects of a breastfeeding campaign on adolescent Korean women.

A sample of 412 Korean adolescent female students were surveyed to determine their attitudes, norms, and intentions toward breastfeeding. Before completing the survey, 207 of the students were exposed to a breastfeeding campaign. A panel presentation and a video stressed the importance and advantages of breastfeeding and presented breastfeeding as a positive experience for mothers. Students exposed to the campaign showed positive attitudes and norms toward breastfeeding and indicated their intent to breastfeed. The control group of 205 students who were not exposed to the campaign showed more positive attitudes and norms toward bottlefeeding and indicated their intent to bottlefeed rather than to breastfeed. Accordingly, a breastfeeding campaign can contribute to promoting positive attitudes and norms toward breastfeeding and to the positive intentions to choose breastfeeding.

Adolescent↗
PubMed1997

Identifying instructional tasks that occasion problem behaviors and assessing the effects of student versus teacher choice among these tasks.

Levels of problem behavior were assessed when 4 students with severe disabilities received instruction on preferred versus nonpreferred tasks and when tasks of each type were chosen by the teacher rather than by the student. In Phase 1, interview and direct observation assessments were conducted to identify relative preferences for academic tasks. In Phase 2, the effects of these lower preference and higher preference tasks on the rate of problem behavior were evaluated using a multielement design. The results showed that lower preference tasks were associated with higher rates of problem behaviors and that students, when given a choice, consistently selected the tasks that had been identified through interview and direct observation as higher preference. In Phase 3, we assessed whether allowing the students to choose between pairs of lower preference tasks or between pairs of higher preference tasks reduced problem behavior relative to a condition in which the teacher selected the same tasks. For 2 of 4 students, the rates of problem behavior were lower when students (rather than the teacher) selected the lower preference activity. Higher preference tasks for 3 students were associated with relatively low rates of problem behavior regardless of whether the student or the teacher selected the task.

Child↗
PubMed2005

Naltrexone reduces the relative reinforcing value of nicotine in a cigarette smoking choice paradigm.

RATIONALE: Human behavioral pharmacology studies can examine how medications that target different neurotransmitter systems influence different aspects of smoking. Naltrexone and bupropion have been shown to alter ad lib smoking behavior; however, medication effects on nicotine reward in a cigarette choice paradigm have yet to be investigated. OBJECTIVE: This study explored the effects of an acute dose of naltrexone, bupropion, or placebo on the relative reinforcing value of nicotine from cigarette smoking using new nicotine and de-nicotinized (Quest, 0.6 and 0.05 mg = "denicotinized") cigarettes. METHODS: In a double-blind, within-subjects design, 26 dependent smokers participated in three experimental cigarette smoking sessions following pretreatment with either naltrexone (50 mg), bupropion (300 mg), or placebo. After medication administration and 2 h of monitored deprivation from cigarettes and food, participants rated their responses to the initial exposure to the cigarettes and then participated in four choice sessions over a 2-h period during which they could take four puffs from either cigarette. RESULTS: The relative reinforcing value of nicotine, as measured by the number of nicotine puffs chosen out of 16, was significantly lower following naltrexone compared to placebo. There were no effects of an acute dose of bupropion on nicotine choices. CONCLUSIONS: These results suggest that naltrexone may reduce the relative reinforcing effects of nicotine via cigarette smoking and support ongoing investigation of opioid antagonists as potential smoking cessation pharmacotherapies.

Adolescent↗
PubMed2002

Operant conditioning.

Operant behavior is behavior "controlled" by its consequences. In practice, operant conditioning is the study of reversible behavior maintained by reinforcement schedules. We review empirical studies and theoretical approaches to two large classes of operant behavior: interval timing and choice. We discuss cognitive versus behavioral approaches to timing, the "gap" experiment and its implications, proportional timing and Weber's law, temporal dynamics and linear waiting, and the problem of simple chain-interval schedules. We review the long history of research on operant choice: the matching law, its extensions and problems, concurrent chain schedules, and self-control. We point out how linear waiting may be involved in timing, choice, and reinforcement schedules generally. There are prospects for a unified approach to all these areas.

Attention↗