Performance of BALB/c and C57BL/6 mice under an incremental repeated acquisition of behavioral chains procedure

BALB/c (n = 8) and C57BL/6 (n = 11) male mice were trained under an incremental repeated acquisition (IRA) procedure using two distinct training procedures: forward and backward chaining. A new metric for assessing progress on the IRA procedure, progress quotient (PQ), quantified progress as the product of chain length and number of reinforcers earned during a session divided by the total number of reinforcers earned. BALB/c mice progressed further, had higher overall responding, earned more reinforcers, and acquired the response sequences faster than the C57BL/6 mice on both training procedures. There were only minimal effects of training procedure for either strain. The strain differences found between BALB/c and C57BL/6 mice confirm the importance of genetic background to behavior. C57BL/6 mice may be deficient in learning as compared with BALB/c mice but other contributing factors probably include overall responding, motivation, and more rapid satiation or habituation to sucrose reinforcement by the C57BL/6 mice. PQ is a sensitive and valid measure of progress for use in studies of mastery-based incremental repeated acquisition and BALB/c mice perform this challenging learning task better than do C57BL/6 mice.     

Assessing motivation in children using a progressive ratio task

The association of age and sex on the performance of a progressive ratio task was studied in 847 children, ages 4-14 years. Variations of this task have been used extensively with animals and to a lesser extent with humans to study factors that affect aspects of motivation. The participants in this study were required to press a response lever for nickel reinforcers during a 10 min period. One response was required to earn the first nickel and each subsequent nickel required an additional 10 more responses. Older children had a significantly higher breakpoint than younger children. This appeared to be mostly the result of older children having significantly shorter inter-response times than younger children. In addition, boys had significantly higher breakpoints than girls, especially at older ages. The results of this study illustrate that both age and sex influence the performance of this task and thus suggest that age and sex influence aspects of motivation in children. Further, characterization of performance of this task by humans facilitates comparisons with animal models and, thus, enhances its translational utility.     

Response sequence difficulty in an incremental repeated acquisition (learning) procedure

Incremental repeated acquisition (IRA) procedures require subjects to learn a different sequence of behavioral responses during each experimental session with required response sequences increasing incrementally in length as subjects demonstrate mastery of shorter response chains. The purpose of this study was to investigate whether some response sequences are more or less difficult to acquire than others. If true, then sequence difficulty must be considered as a potential confound when attempting to assess the effects of drugs and other experimental manipulations on learning. Accuracy for each response sequence was assessed using control data from two large rodent studies, and each sequence was classified as easy, moderate or hard. Sequences that required responses on adjacent levers were easier (characterized by higher accuracies) to acquire than those that required responses on non-adjacent levers. In addition, sequences that required responses on only two of three response levers were easier to acquire than those that required responses on all three levers. These results provide strong evidence for differing levels of response sequence difficulty in IRA procedures with sequence difficulty seeming to be dependent on whether or not responses are required on adjacent levers.     

Modification of the repeated acquisition of response sequences in rats by low-level microwave exposure

The acute effects of microwave exposure on a repeated acquisition baseline were investigated in three rats. Each session the animals acquired a different four-member response sequence. Each of the first three correct responses advanced the sequence to the next member, and the fourth correct response produced food reinforcement. Incorrect responses produced a three-second timeout. Baseline and control sessions were characterized by a decrease in errors within each session. The animals were acutely exposed to a 2.8 GHz pulsed-microwave field prior to test sessions, with average power densities ranging from 0.25 to 10 mW/cm². In comparison to control sessions, 1/2 hour of exposure to microwave radiation at power densities of 5 and 10 mW/cm² increased errors and altered the pattern of within-session acquisition. Exposure to the 10 mW/cm² power density decreased the rate of sequence completion in all animals. The results of exposures at 0.25, 0.5, and 1 mW/cm² power densities were generally within the control range. The results are interpreted as indicating a disruption in the discriminative stimulus control of the repeated acquisition behavior.     

Effects of luteolin on learning acquisition in rats: involvement of the central cholinergic system

The study was conducted to investigate the ameliorating effects of luteolin on memory acquisition in rats. The effects of luteolin on scopolamine-induced impairment of passive avoidance response were evaluated primarily, as well as the role of the central nervous system through the use of central neurotoxins and central nervous antagonists. Luteolin was not reversed by scopolamine N-methylbromide (M-SCOP) but blocked the impairment of learning acquisition induced by cholinergic neurotoxin (ethylcholine aziridinium, AF64A) and muscarinic (scopolamine hydrobromide, SCOP) and nicotinic (mecamylamine, MECA) receptor antagonists. However, it did not block dopaminergic neurotoxin (6-hydroxydopamine, 6-OHDA)-induced and serotonergic neurotoxin (5,7-dihydroxytryptamine, 5,7-DHT)-induced impairments. From these results, we suggest that the attenuating effect of luteolin (10 mg/kg, i.p.) on the deficits of passive avoidance performance induced by SCOP may be related to the increases in the activities of central muscarinic and nicotinic receptors.     

Female mini-pig performance of temporal response differentiation, incremental repeated acquisition, and progressive ratio operant tasks

Increased knowledge of the cognitive abilities of mini-pigs is needed due to their increasing use in behavioral neuroscience research. Here, six female Yucatan mini-pigs performed tasks thought to measure timing behavior (temporal response differentiation, TRD), learning (incremental repeated acquisition, IRA), and motivation (progressive ratio, PR). Daily 30-min sessions for food reinforcers required a lever press be maintained for at least 10 but no longer than 14s (TRD), learning a new sequence of lever presses each test day (IRA) or an escalating number of presses for subsequent reinforcers (PR). All animals performed PR two days/week while three performed TRD five days/week and the other three performed IRA five days/week. Over the four test weeks, no animal completed TRD training and only one appeared to progress. For this task, lever press maintenance appeared difficult since by choice, the pigs used a front hoof, rather than the snout, to press the lever. IRA subjects showed gradually increasing performance with response rates comparable to those of rats but below those of children and monkeys and accuracy below that for rats. PR response rates were higher than those typically reported for rats, but lower than for adult rhesus monkeys or children. Physical differences in the way that each species responds likely account for these differences.     

儿童肠道菌群的建立及影响因素研究进展

早期肠道菌群的建立与机体长远的健康状况密切相关,儿童肠道菌群具有动态、脆弱的特点,孕期菌群暴露、出生途径、喂养方式、出生环境、抗生素使用以及添加益生菌等多种因素均可影响其形成和功能;本文就相关影响因素研究进展进行综述.     

Proximity to an edge affects search strategy in adults and children

When searching for a hidden goal, search patterns are often defined according to one of two main search strategies: an absolute strategy, which usually involves searching at a fixed learned distance and direction from a particular reference point, or a relational strategy, which involves searching at a point that maintains the relationship between two or more other points. Past research has shown that humans tend to prefer a relational strategy whereas most non-humans prefer an absolute strategy. However, recent research (Hartley et al., 2004) used a simulated 3D environment to demonstrate that proximity to a boundary affects strategy. In particular, when searching close to an edge, human participants were more likely to use an absolute strategy whereas when searching at a central location, participants were more likely to use a relational strategy. The current studies extend the findings of Hartley et al. Experiment 1 showed that adult humans use different strategies based on the goal's proximity to the edge of a search space, and that strategies differed between males and females. Experiment 2 suggested that children also use different strategies based on the goal's proximity to a boundary, and that some goal locations may be harder to learn than others. Taken together, our results show that search strategies are flexible and context-specific.     

Motor functions but not learning and memory are impaired upon repeated exposure to sub-lethal doses of methyl parathion

Summary Our previous work showed that repeated exposure to methyl parathion (MP) caused a prolonged inhibition of acetylcholinesterase (AChE) activity (∼80%) and down-regulation of M₁ and M₂ muscarinic receptors (up to 38%) in rats at brain regions, including frontal cortex, striatum, hippocampus and thalamus. In the present neurobehavioral study, we found this repeated MP treatment had suppressant effects on rat’s locomotor activity. However, we observed no evidence of long-term effects of MP on associative learning and memory. Our data demonstrated that repeated exposure to MP caused some functional deficits in CNS, but motor activity and associative learning/memory process might differ in the sensitivity to its toxic effect. The motor dysfunctions in MP-treated rats may be mediated via reciprocal balance between cholinergic and dopaminergic systems at striatum following cholinergic over-stimulation. Our findings also suggest that the CNS deficits induced by repeated exposure to MP or other organophosphate (OP) pesticides cannot be attributed entirely to the inhibition of AChE. To accurately assess the neuro-toxic risk by occupational exposure to sub-lethal doses of MP, novel biomarkers besides in vivo anticholinesterase potency are needed.     

Expression of an artificial polypeptide with a repeated tripeptide glutamyl-tryptophanyl-lysine in Saccharomyces cerevisiae

AIMS: Artificial genes, which encode 48 or 64 repeats of a tripeptide, glutamyl-tryptophanyl-lysine have been cloned to the yeast expression vector pAM82 containing the PHO5 promoter and expressed in Saccharomyces cerevisiae AH22. METHODS AND RESULTS: When the yeast cells harbouring recombinant plasmids pALTG6-2 and pALTG4-4 were derepressed in Burkholder minimal medium (Toh-e, A., Ueda, Y., Kakimoto, S.I. and Oshima, Y. (1973) Journal of Bacteriology113, 727-738) containing low phosphate (0.03 g l-1 KH2PO4 and 1.5 g l-1 KCl), the expression was the highest after 24 h induction and the artificial polypeptides were synthesized to about 10% (pALTG6-2) and 14% (pALTG4-4) of the total cell protein. CONCLUSIONS: The artificial polypeptides produced in yeast were made to react with the rabbit antiserum against the polypeptide purified from Escherichia coli and found only in the pellet fraction of cell lysates, indicating the formation of inclusion body. Artificial polypeptide consisting of Glu-Trp-Lys may be useful as partial supplement in food and feeds. SIGNIFICANCE AND IMPACT OF THE STUDY: The production of single cell enriched with homopolymers of an essential amino acid in yeast might be an important tool of supplementing cereal diets and feed grain rations and could be used as means for improvement of the amino acid profile of single cell protein and production of pharmaceutical peptides.     

奖励性操作式条件反射任务在大鼠学习记忆研究中的应用

目的将奖励性操作式条件反射方法应用于学习记忆研究。方法首次采用奖励性操作式条件反射方法,设置单次操作训练、连续多次操作训练、信号辨识与消退四种检测模式,研究Wistar大鼠和SHR大鼠学习记忆能力。结果奖赏训练中,SHR组鼻触次数显著增多（vs.Wistar＆Donepezil,P〈0.05）;单次操作训练中,三组动物对操作反应的获得无显著差异;连续多次操作学习任务中,SHR组错误操作次数增多（vs.Wistar,P〈0.05）,奖赏获得次数减少（vs.Donepezil,P〈0.001）,反应准确率显著降低（vs.Wistar＆Donepezil,P〈0.05）;信号辨识任务中SHR组错误反应次数显著增多（vs.Wistar＆Donepezil,P〈0.05）,而反应准确率降低,组间差异有显著性（vs.Wistar＆Donepezil,P〈0.05）;消退实验中,三组动物差异无显著性。神经递质检测发现,SHR组大鼠谷氨酸[（1.0639±0.07086）mg/g]、乙酰胆碱[（2.7760±0.2609）μg/g]与五羟色胺[（1.2200±0.1137）μg/g]含量均显著低于Wistar组大鼠（P〈0.05）,多奈哌齐组大鼠乙酰胆碱含量显著增加[（3.9344±0.2747）μg/g]（vs.Wistar,P〈0.05;vs.SHR,P〈0.001）。结论奖励性操作式条件反射方法可作为一种正性增强条件反射检测新方法应用于大鼠学习记忆研究。     

Response strategies during acquisition of serial learning in pigeons (Columba livia)

Pigeons were exposed on fixed duration sessions to four chromatic stimuli and trained to perform a 2-item sequence. A detailed analysis of incorrect responses performed on each trial prior to completion of the sequence led to distinguish three learning stages. Already on initial sessions animals responded significantly more frequently to relevant stimuli than to irrelevant ones indicating stimulus control by salience. During an intermediary stage, responding to item 2 increased significantly and animals started an increasing number of trials with item 2, suggesting stimulus control by recency. On the final session the correct sequence outnumbered significantly the reverse sequence, suggesting control by order, while recency and salience effects were present to a lesser extent. Repeated pecks, i.e. consecutive pecks on the same cue, occurred on the four cues on the first session and decreased significantly on the last session for irrelevant colours. In addition, when key pecks were followed by a brief sound signal, repeats on relevant stimuli decreased while efficient colour pecks (i.e. when repeats were ignored) on these stimuli increased. These findings are discussed in the light of those obtained in traditional chaining paradigms.     

Light acquisition and use by individuals competing in a dense stand of an annual herb, Xanthium canadense

The importance of light acquisition and utilization by individuals in intraspecific competition was evaluated by determining growth and photosynthesis of individual plants in a dense monospecific stand of an annual, Xanthium canadense. Photosynthesis of individual plants in the stand was calculated using a canopy photosynthesis model in which leaf photosynthesis was assumed to be function of leaf nitrogen content and light availability. The estimated photosynthetic rates of individuals were strongly correlated with the measured growth rates. Photosynthetic rates per unit aboveground mass (RPR, relative photosynthetic rate) increased with increasing aboveground mass, suggesting asymmetric (one-sided) competition in the stand. However, larger individuals had similar RPRs, suggesting symmetric (two-sided) competition. These results were consistent with the observation that size inequality over the whole stand increased with growth, but it remained stable among the larger individuals. The RPR of an individual was calculated as the product of absorbed photon flux per unit aboveground mass (Φ_mass) and light use efficiency (LUE, photosynthesis per unit absorbed photon flux). Φ_mass indicates the efficiency of light acquisition, and was higher in larger individuals in the stand, while LUE was highest in individuals with intermediate aboveground mass. LUE depends on leaf nitrogen content. At an early stage, leaf nitrogen contents of smaller individuals were similar to those that maximize LUE. Light availability to smaller individuals decreased as they grew, while their nitrogen contents did not change markedly, which decreased their LUE. We concluded that asymmetric competition among individuals in the stand resulted mainly from lower efficiencies in both light acquisition and light use by smaller individuals. Received: 31 January 1998 / Accepted: 12 November 1998     

Discontinuous and incremental processes in the song learning of birds: evidence for a primer effect

Studies on the song learning in birds revealed a puzzling property of the acquisition system: Stimulus memorization becomes effective after remarkably few exposures, but nevertheless shows a relationship to the frequency of exposure to learning stimuli. This raises questions on the amount of learning that will occur during a given exposure to song. To examine this issue, we tutored handraised fledgling nightingales (Luscinia megarhynchos) with song strings, in which the serial succession of species-typical master songs was altered upon subsequent exposures. The sequencing of imitations obtained from the birds' adult singing revealed the following results: (1) A single exposure was sufficient for subjects to acquire serial information on song-type sequencing. (2) The first exposure to a master string played a key role for this accomplishment. (3) Nevertheless, the acquisition of serial information improved with increasing exposure frequency of master strings. (4) The acquisition of song patterns was not impaired by a non-regular presentation of master song-types. With respect to the particular salience of the first exposure for sequence memorization, we termed the phenomenon primer effect. The findings suggest that stimulus acquisition during perceptual song learning is mediated by a discontinuous process. Once acquired, information is then consolidated gradually, i.e. through an incremental process.     

The use of an automated assay to assess phage survival after a biocidal treatment

The coliphage K_1-5 has been used in an automated assay to monitor the viricidal activity of various disinfectants. This indirect assay based on the spectrophotometric reading of the lysis of the host cell ( Escherichia coli D837) produced encouraging results and was faster than the overlay counting method (previously studied) which relies on plaque formation. However, differences in sensitivity towards some disinfectants were observed between the two methods.     

The use of erythrocyte fragility to assess xenobiotic cytotoxicity

The erythrocytes of mammals represent a good model to evaluate the cytotoxicity of molecules, organic and inorganic, natural or synthetic, by cellular damage measure. Indeed, before any investigation on the mechanism of action of different molecules, it is important to perform a cytotoxicity assay. Among the different cytotoxicity assays that assess a possible toxicity in the red blood cells is the rate of haemolysis. This essay is based on the evaluation of the alterations of red cell membranes in the presence of an eventual xenobiotic. Red blood cells are the main cells in circulation, and they are responsible for transporting oxygen; in fact, any alterations of this process could be lethal. The plasma membrane of red blood cells is a multi‐component structure such as to confer to these cells their characteristic biconcave shape, high flexibility, elasticity and deformability. However, there are clear signs of cellular suffering if there are any alterations to this structure. One method of toxicity assessment is based on measurement of the efflux of haemoglobin from suspended red blood cells. Haemolysis, and therefore the loss of haemoglobin, is the signal stability of the cell membrane of the erythrocytes. In recent years, the discovery of programmed cell death in mammalian red blood cells presented a diversification of the response to injury by these a‐nucleated cells. This review shows that mammals' erythrocytes might serve well as a model cell to study on the cellular and molecular mechanisms of many treatments. Copyright © 2015 John Wiley & Sons, Ltd.     

The use of actimetry to assess changes to the rest-activity cycle

The endogenous circadian oscillator (the body clock) is slow to adjust to altered rest-activity patterns. As a result, several negative consequences arise during night work and after time-zone transitions. The process of adjustment can be assessed by measurements of the sleep electroencephalogram (EEG), core temperature or melatonin secretion, for example, but these techniques are very difficult to apply in field studies, and make very great demands upon both experimenters and subjects. We have sought to establish if the activity record, measured conveniently and unobtrusively by a monitor attached to the wrist, can be treated in ways that enable estimates to be made of the disruption caused by changes to the rest-activity cycle, and the process of adjustment to them. In Part A, we describe the calculation and assessment of a series of “activity indices” that measure the overall activity pattern, activity when out of bed or in bed, or the activity in the hours adjacent to going to bed or getting up. The value of the indices was assessed by measuring changes to them in subjects undergoing night work or undergoing time-zone transitions. In both cases, there is a large body of literature describing the changes that would be expected. First, night workers (working 2 to 4 successive night shifts) were investigated during rest days and night shifts. The indices indicated that night work was associated with lower activity when the subjects were out of bed and higher activity when in bed. Some indices also measured when subjects took an afternoon nap before starting a series of night shifts and gave information about the process of adjustment to night work and recovery from it. Second, in studies from travelers crossing six or more time zones to the east or west, the indices indicated that there were changes to the rest-activity cycle immediately after the flights, both in its overall profile and when activity of the subjects in bed or out of bed was considered, and that adjustment took place on subsequent days. By focusing on those indices describing the activity records during the last hour in bed (LHIB) and the first hour out of bed (FHOB), some evidence was found for incomplete adjustment of the body clock, and for differences between westward and eastward flights. In Part B, the battery of indices are applied to the activity records of long-haul pilots, whose activity patterns showed a mixture of effects due to night work and time-zone transitions. Actimetry was performed during the flights themselves and during the layover days (which were either rest or work days). The indices indicated that all pilots had disrupted rest-activity cycles caused by night flights, and that there were added problems for those who had also undergone time-zone transitions. Rest days were valuable for normalizing the activity profile. For those pilots who flew to the west, adjustment was by delay, though not all aspects of the rest-activity cycle adjusted immediately; for those who flew to the east, some attempted to advance their rest-activity cycle while others maintained home-based activity profiles. The indices indicated that the activity profile was disrupted more in those pilots who attempted to advance their rest-activity cycle. We conclude that objective estimates of the disruption caused to the rest-activity cycle and the circadian system can be obtained by suitable analysis of the activity record.     

Population structure of Plasmodium falciparum gametocyte sex ratios in malarious children in an endemic area

The gametocyte sex ratio (proportion of gametocytes that are male) of Plasmodium falciparum may influence transmission. The distribution of P. falciparum sex ratios, the extent of inbreeding, the relationship between clone multiplicity and sex ratio, and the pre- and post-treatment factors influencing a sex ratio of 0.5 were determined in 1609 children, with acute malaria. Gametocytes were sexed by morphological appearance and asexual clone multiplicity was determined by polymerase chain reaction (PCR) using polymorphic loci of merozoite surface proteins-1 and -2 (MSP-1, MSP-2) and glutamine-rich protein (GLURP). The weighted mean population sex ratio on presentation in 162 gametocyte carriers was 0.22, that is, 3.5 female to 1 male (95% CI 0.15–0.28), with an estimated inbreeding rate (f) (the proportion of a mother's daughters that is fertilized by her sons) of 0.56 (95% CI 0.44–0.70). Sex ratio was significantly higher when clone multiplicity was >1 infecting clone than when it was 1 (P = 0.02). The frequency of a pre-treatment sex ratio of 0.5 was low (3%), and was significantly increased by non-artemisinin but not by artemisinin – mono or combination – drugs by day 7 after therapy commenced (P = 0.03 and P = 0.44, respectively). No factor was associated with a pre-treatment sex ratio of 0.5 but two factors were independent predictors of a sex ratio of 0.5 by day 7 after therapy commenced: an age ≥5 years and anaemia. These population data provide some empirical support for the predictions of local mate competition (LMC) theory and, in conjunction with effects of antimalarials on a sex ratio of 0.5, may have implications for malaria control efforts in endemic settings.     

年龄和性别因素对封闭群草原兔尾鼠正常血液生化指标的影响

目的　探讨性别和年龄因素对封闭群草原兔尾鼠正常血液生化指标的影响。方法　利用雅培(AEROSET)全自动血液生化测定仪对雄性组、雌性组、1月龄 2月龄组和 2 4月龄组封闭群草原兔尾鼠的 2 3项血液正常生化指标进行了测定。结果　两年龄组各指标间以及两性别组各指标间均无统计学差异。结论　本实验中封闭群草原兔尾鼠的性别因素和年龄 (1月龄 - 2月龄年龄段和 2 4月龄年龄段 )因素对测定的 2 3项正常血液生化指标没有显著影响。