Behavioral Profiles of Genetically Selected Aggressive and Nonaggressive Male Wild House Mice in Two Anxiety Tests

Artificially selected aggressive (SAL) and non-aggressive (LAL) male house mice were tested in a hexagonal tunnel maze and light-dark preference (LD) box to determine if the bidirectional selection for aggressive behavior leads to a coselection for different levels of trait anxiety. The tunnel maze consists of an open, brightly lit central arena surrounded by a complex system of interconnecting tunnels. As in the LD box, animals which spend less time and are less active in the brightly illuminated section of the maze are considered to have higher anxiety levels. In the tunnel maze, the LAL mice showed more exploration and spent more time in the central arena than the SAL animals, but only during the final 2 min of the 6-min test. This reduced preference for the central arena was not due to general inactivity or a failure of the SAL to find the central arena and indicates a higher level of state anxiety in the aggressive animals. In contrast, no anxiety-like differences were found in the LD box, either for the percentage of time spent in the light compartment or for the number of crossings. SAL males actually showed higher levels of moving and rearing, and lower levels of freezing, than did LAL males.     

Seven generations of genetic selection for ethanol dependence in mice

An animal model of alcohol dependence is being produced by selecting mice for differences in severity of ethanol withdrawal seizures. Replicate lines of high-dependence (HA), low-dependence (LA), and control (CA) mice are being developed by within-family selection. After seven generations both (replicate) HA and LA lines have separated significantly. Some of the difference between the replicate pairs of HA and LA in the early generations was due to differences in ethanol consumption. This difference in consumption may be attributable to a difference in metabolic rate or activity level rather than to a difference in ethanol preference. Females are more susceptible to seizures than males; this appears to be due partly to their higher consumption of ethanol during treatment.This research was supported in part by Grant AA-03527 from the National Institute of Alcohol Abuse and Alcoholism to the University of Colorado Alcohol Research Center.     

Development of autoimmune insulitis is prevented in E alpha d but not in A beta k NOD transgenic mice

Two lines of E alpha d-expressing NOD mice were established by continuously backcrossing [E alpha d B6 transgenic mice x NOD] F1 to parental NOD or directly microinjecting the E alpha d gene into fertilized NOD eggs. Similarly, A beta k-expressing transgenic NOD mice were produced. Subsequent histological examination of pancreatic tissues revealed that autoimmune insulitis was prevented in E alpha d backcross and transgenic mice but not in A beta k transgenic mice.     

Effectiveness of divergent selection for open-field activity in rabbits and correlated response for body weight and fertility

Two lines deriving from the same rabbit stock were selected for 8 generations for high (H) or low (L) locomotor activity score in the open field (OFS). The divergent selection was most effective up to the 3rd generation in the H line and up to the 4th generation in the L line. In further generations a decrease of OFS in the H line and a floor effect (OFS = 0) in the L line were observed. The mean OFS increased significantly in consecutive trials in the H line, whereas this increase was non-significant in the L line. There was a negative and very high correlation between the latency to enter the open field and the OFS (–0.95 and –0.98 for the H and L line, respectively). The realized heritability of the OFS was 0.46 and 0.23 in generations 0–3 within the L and H line, respectively, and 0.44 and –0.06 in generations 0–8. As calculated on the basis of divergent selection, the heritability was 0.31 and 0.15 for generations 0–3 and 0–8, respectively. The L rabbits were heavier shortly before (4th wk, P < 0.001) and after (8th wk, P < 0.01) weaning, than those of the H line, whereas the H rabbits grew faster (P < 0.05) between the 4th and 20th wk of age. There was a tendency for decreasing weight gains in consecutive generations. Generally, a lower percentage of H females delivered litters than those of the L line, but this was due to a very low percentage of such females in the 3rd and 6th generations. It can be assumed that H and L lines represent different, i.e., active and passive, coping strategies. These lines of rabbits offer increased possibilities for physiologically and ethologically oriented studies, e.g., on the welfare of caged animals.     

Effect of the serotonin agonist buspirone on behaviour and hypothalamic-pituitary-adrenal axis in confident and fearful mink

Behavioural and hypothalamic-pituitary-adrenal (HPA) axis responses were investigated in farm mink (Mustela vison) selected for either confident or fearful behaviour for nine generations.Two groups of 2-year-old confident (n=12) and fearful (n=12) female mink were given the serotonin (5-HT) 1A receptor agonist buspirone (1.25 mg/kg/day), whereas two other groups of 2-year-old confident (n=12) and fearful (n=12) female mink were given saline, continuously for 5 weeks via osmotic minipumps. Behavioural reactions towards a novel object and towards humans were tested after 19-25 days, and HPA axis reactivity [adrenocorticotropic hormone (ACTH), cortisol] was measured after 28-31 days of treatment. Confident mink were more exploratory than fearful mink towards humans and a novel object. Confident mink spent more time in contact with the object than did fearful mink during saline-but not during buspirone-treatment. buspirone increased approach-withdrawal conflict behaviour towards a object in fearful mink only. The chronic dose of buspirone did not reduce fear towards humans and did not affect latencies to reaction, number of contacts, number and duration of manipulations, and stereotypic behaviour in a Novel Object test. Different HPA axis responses have emerged between confident and fearful mink, together with a different degree of fear-related behaviour. Fearful mink have a higher cortisol combined with a lower ACTH secretion than confident mink in response to capture and blood sampling. The central serotonergic system may be involved, and even though the precise underlying mechanisms are presently unknown, treatment with a 5-HT(1A) receptor agonist reduces the difference between confident and fearful mink in HPA axis reactivity.     

Dopamine in the orbitofrontal cortex regulates operant responding under a progressive ratio of reinforcement in rats

Prefrontocortical dopamine (DA) plays an essential role in the regulation of cognitive functions and behavior. The orbitofrontal cortex (OFC) receives a dopaminergic projection from the ventral tegmental area and is particularly important for goal-directed appetitive behaviors and for the neural representation of reward value. We here examined the effects of DA receptor blockers locally infused into the OFC, on instrumental behavior under a progressive schedule of reinforcement. After continuous reinforcement training (lever pressing for casein pellets) rats received bilateral intra-OFC-infusions of the DA D1-receptor antagonist SCH23390 (3 μg/0.5 μl), the DA D2-receptor antagonist sulpiride (3 μg/0.5 μl), or phosphate buffered saline through chronically indwelling cannulae. Immediately after infusion they were tested under a time-constrained progressive ratio schedule of reinforcement (3, 6, 9, 12, … lever presses for 1 casein pellet within 180 s). Both SCH23390 and sulpiride led to a significant reduction of the break point (cessation to respond to the increasing criterion of instrumental effort) compared to vehicle infusions. A food preference test revealed no drug effects on the amount of consumed pellets and on the preference of casein pellets over laboratory chow. Leftward shifts of the break point in progressive ratio tasks indicate a disturbance of the mechanisms that translate motivation into appetitive behavior under conditions of increasing instrumental effort. Therefore, our data indicate that orbitofrontal dopamine is necessary for reward-related instrumental behavior.     

Inbreeding Affects Female Preference for Symmetry in Computer-Animated Sticklebacks

Fluctuating asymmetries are small random deviations from perfect symmetry in bilateral traits caused by the inability of individuals to cope with stress during development. The degree of asymmetry of secondary sexual characters is supposed to convey information about a male's phenotypic and/or genetic quality, and females are thus expected to use bilateral symmetry as a cue in mate choice. We offered female three-spined sticklebacks (Gasterosteus aculeatus L.) that had been inbred for one generation and outbred control females the choice between computer-animated male models differing exclusively in the symmetry of their pelvic spines. Inbred females exhibited a significantly stronger preference for the symmetric model than outbred females, suggesting that females of relatively poor quality are more prepared to pay the costs of choosiness and obtain higher marginal benefits from their discrimination than females of better quality.     

Structure, genomic DNA typing, and kinetic characterization of the D allozyme of placental alkaline phosphatase (PLAP/ALPP)

The D allozyme of placental alkaline phosphatase (PLAP) displays enzymatic properties at variance with those of the common PLAP allozymes. We have deduced the amino acid sequence of the PLAP D allele by PCR cloning of its gene, ALPP. Two coding substitutions were found in comparison with the cDNA of the common PLAP F allele, i.e., 692C>G and 1352A>G, which translate into a P209R and E429G substitution. A single nucleotide primer extension (SNuPE) assay was developed using PCR primers that enable the amplification of a 1.9 kb PLAP fragment. Extension primers were then used on this PCR fragment to detect the 692C>G and 1352A>G substitution. The SNuPE assay on these two nucleotide substitutions enabled us to distinguish the PLAP F and D alleles from the PLAP S/I alleles. Functional studies on the D allozyme were made possible by constructing and expressing a PLAP D cDNA, i.e., [Arg209, Gly429]PLAP, into wild-type Chinese hamster ovary cells. We determined the k(cat) and K(m), of the PLAP S, F, and D allozymes using the non-physiological substrate p-nitrophenylphosphate at an optimal pH (9.8) as well as two physiological substrates, i.e., pyridoxal-5-phosphate and inorganic pyrophosphate at physiological pH (7.5). We found that the biochemical properties of the D allozyme of PLAP are significantly different from those of the common PLAP allozymes. These biochemical findings suggest that a suboptimal enzymatic function by the PLAP D allozyme may be the basis for the apparent negative selective pressure of the PLAP D allele. The development of the SNuPE assay will enable us to test the hypothesis that the PLAP D allele is subjected to intrauterine selection by examining genomic DNA from statistically informative population samples.     

基于F-score特征选择和支持向量机的P300识别算法

如何从脑电信号中快速准确地识别出P300成分是脑-机接口研究中的一个热点问题.针对P300的识别问题,我们提出了一种将F-score特征选择与支持向量机相结合的判别方法,该方法采用F-score特征选择减少输入特征的维数,以克服支持向量机算法判别速度慢的缺点;然后借助支持向量机算法良好的分类性能实现P300的识别.本文在BCI Competition 2003的P300实验数据集上对该方法进行了验证,结果表明,在5次重复实验中该方法的识别准确率达到了100%,且判别速度与未经特征选择的传统支持向量机算法相比提高了近2倍.     

Establishment of human osteosarcoma cell lines with high metastatic potential to lungs and their utilities for therapeutic studies on metastatic osteosarcoma

Relevant animal models for metastasis of osteosarcoma is needed to understand the biology and to develop the treatment modality of metastasis of human osteosarcoma. Therefore, we screened six human osteosarcoma cell lines for metastatic ability in nude mice. The HuO9 cell line was identified as being metastatic to the lung after intravenous injection. We established two sublines, HuO9-M112 and HuO9-M132, with high metastatic potential to the lung from the parental HuO9 cells by in vivo selection. There were no differences between these two sublines and the parental cells in the growth rate in vitro and the tumorigenicity after subcutaneous injection in nude mice, however, mice injected with the metastatic sublines became moribund earlier than mice injected with the parental HuO9 cells did. Thus, adriamycin (ADR) and recombinant interleukin-12 (IL-12) were administered to mice injected with the HuO9-M112 subline to suppress experimental lung metastases. Production of lung colonies was significantly suppressed and the prognoses of mice were significantly improved by both ADR and IL-12 treatments. These results indicate that both ADR and IL-12 are effective agents against pulmonary metastatic osteosarcoma, and that these sublines are useful for studies on the biological behavior and treatment of pulmonary metastatic osteosarcoma. This revised version was published online in July 2006 with corrections to the Cover Date.