Detection of new spider toxins from a Nephilengys borbonica venom gland using on-line mu-column HPLC continuous flow (FRIT) FAB LC/MS and MS/MS

The Morris water maze is frequently used to screen mutant mice generated by gene targeting. Targeted ES-cells are often derived from 129/Sv or BALB/c mice, known as poor swimming navigation learners. After mating the founders with C57BL/6 mice, the F2 or F3 hybrid generation is typically used for behavioral testing. In hybrid 129/Sv x C57BL/6 mice, a modification of the betaAPP gene entails impaired swimming navigation learning. This is readily detected despite behavioral variability, because wild-type 129/Sv x C57BL/6 hybrids outperform either of the parental strains and provide a control sample with good baseline performance. However, after backcrossing to the 129/Sv(ev) strain, the mutation effects are no longer detectable, masked by the very poor performance of wild-type 129/Sv(ev) mice. We conclude that F2 and F3 generations of 129/Sv x C57BL/6 crosses provide a suitable genetic background for behavioral testing of transgenic mice, provided that the samples are large enough to compensate for genetic and epigenetic variability and provided that normal performance in the control group is verified by comparison against a large database of mice tested under identical conditions. Creating congenic lines by backcrossing to an inbred strain is unlikely to enhance the sensitivity of the Morris test. Backcrossing to 129/Sv(ev) may even reduce it.     

Hippocampal lesions cause learning deficits in inbred mice in the Morris water maze and conditioned-fear task.

This study examined the effect of hippocampal lesions on acquisition of the Morris water maze and conditioned-fear task in inbred mice. C57BL/6J, DBA/2J, and B6D2F1 hybrid mice were given hippocampal lesions or sham surgery and then tested. The lesioned C57BL/6J and B6D2F1 mice failed to learn the Morris task relative to sham-operated controls, and no DBA group learned the task. In the contextual component of conditioned fear, lesions decreased freezing in all strains. But the lesions only affected freezing to the conditioned stimulus in the DBA/2J and B6D2F1 strains. These data demonstrate that C57BL/6J and B6D2F1 mice use the hippocampus to solve the Morris water maze and conditioned-fear task, and the DBA mice use the hippocampus, to some degree, in the conditioned-fear task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Daily glucose injections facilitate performance of a win-stay water-escape working memory task in mice.

In an experiment that compared 3 versions of a working memory task, male C57BL/6 mice given either 3 (n?=?7) or 5 (n?=?7) opportunities (test runs) per trial to choose the escape choice section of a maze acquired a win–stay (spatial matching-to-sample) water-escape task. Mice given only 1 test run per trial (n?=?6) were unable to perform above chance level. In a 2nd experiment, 14 mice from the 1st experiment were tested for performance on the 3-test-run version of the task. Each mouse was tested for 12 consecutive days with each of 4 doses of glucose (0, 50, 100, and 250 mg/kg ip) given 30 min before testing. The 2 higher doses increased the percentage of correct test run choices on all 3 daily test runs across the 12 days of testing. Daily glucose injections facilitated the use of trial-dependent information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Further Evidence That Mice Learn a Win-Shift but Not a Win-Stay Contingency Under Water-Escape Motivation.

Previous research (C. Locurto, C. Emidy, & S. Hannan, 2002) indicated that mice quickly learned a water-escape task under a win-shift contingency but did not exceed chance-level performance under a win-stay contingency. We examined the robustness of this conclusion in two experiments by varying procedural and temporal aspects of that earlier experiment. Results of both experiments indicated that the preference for win-shift learning in mice under water-escape motivation could not be attributed to procedural or design features of that earlier study and were independent of the influence of intertrial interval, normally a variable that produces strong effects on learning. In neither experiment did subjects exposed to a win-stay contingency perform at above-chance levels. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A case of behavioral heterosis in mice: Quantitative and qualitative aspects of performance in a water-escape task.

1,404 mice from 2 inbred strains (BALB/c and C57BL/6), F?, F?, and backcrosses were subjected to 4 trials in a water-escape task and a swimming test. Detailed analysis of Ss' behavior in these situations showed that the "F? hybrid vigor" affected behavioral characters not directly related to physical vigor but of potential adaptive value. Their superiority was mainly due to more frequent adoption of an efficient behavioral tactic (direct or edge escape paths toward the exit) and more rapid progress with experience in this respect than other generations exhibited. Results show that heterosis is not limited to physical vigor but may extend to behavioral and even psychological characters. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Traumatic brain injury causes delayed motor and cognitive impairment in a mutant mouse strain known to exhibit delayed Wallerian degeneration

Delayed Wallerian degeneration after neuronal injury is a feature of the C57BL/Wld(s) mouse mutant. In the present study, we examined the effect of unilateral controlled cortical impact (CCI) on motor and cognitive performance in C57BL/6 and C57BL/Wld(s) mice. Performance on a beam-walking task was impaired in both injured groups over the first 3 weeks; however, between 28 and 35 days post injury, C57BL/6 mice continued to improve whereas C57BL/Wld(s) mice showed increased footfaults. In a spatial learning task, C57BL/Wld(s) animals performed consistently better than C57BL/6 mice when tested 7-10 days and 14-17 days following CCI. C57BL/Wld(s) mice also demonstrated improved working memory performance as compared with C57BL/6 mice when trained on days 21-22 after injury; this effect was lost on days 23 and 24, and was not evident in other animals tested in the same task at 28-31 days following injury. These results indicate a marked delay in motor and cognitive impairment following CCI in C57BL/Wld(s) mice compared with injured C57BL/6 controls. This is consistent with previous work showing delayed temporal evolution of neuronal degeneration in C57BL/Wld(s) mice and suggests CCI may be a suitable model for examining the functional consequences of traumatic brain injury (TBI) in genetically altered mice.     

Effects of pimozide on escape and discrimination performance in a water-escape task.

Three experiments studied the effects of pimozide (0.2 and 0.4 mg/kg) on discrimination learning of 255 male CD1 mice in a water-escape paradigm in which the degree of motor difficulty was manipulated by varying water temperature. The drug marginally affected escape latencies in relatively warm water (25°C) but markedly disrupted escape latencies when the task was more demanding (e.g., 15 and 20°C water). The escape deficits, however, were not accompanied by disturbances in the acquisition of position discrimination or cue discrimination responses when Ss were required to make the highly prepared response of swimming to light or the contraprepared response of swimming to dark. Data suggest that in tasks involving aversive motivation, pimozide influences performance through its effects on response maintenance but does not appear to affect either associative or motivational processes. (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex differences in learning and memory in mice: Effects of sequence of testing and cholinergic blockade.

Sexual dimorphism in spatial and cued navigation using the Morris water maze was examined in C57BL/6 mice both with and without administration of scopolamine, a cholinergic blocker. In Exp 1, female and male mice learned to perform first a spatial, then a cued, navigation task. Both performed a spatial task similarly; males, however, performed a cued task better than females. In Exp 2, the sequence of navigation testing was reversed. Both performed similarly on a cued task; however, males performed a spatial task better than females. In both experiments, females were more sensitive than males to the effects of scopolamine. No significant confounding sex differences were found in either spontaneous activity or passive avoidance retention. These data indicate that sex differences in spatial and cued tasks are dependent on the sequence of task presentation and implicate a role for the cholinergic system in these differences. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Swimming navigation, open-field activity, and extrapolation behavior of two inbred mouse strains with Robertsonian translocation of chromosomes 8 and 17

Female mice from inbred strains carrying a Robertsonian translocation (nine CBARb and eight C57BL/6Rb) were compared with animals from their respective strains (seven CBA and nine C57BL/6) first in open-field activity (two exposures of 10-min duration), then during 5 days (with six trials each) in Morris' swimming navigation test, and finally, in their ability to extrapolate the future position of a food reward being moved slowly out of their reach. ANOVA (strain and translocation) revealed significant effects of Robertsonian translocations (Rb) in swimming navigation, Rb mice being impaired primarily in the initial phases of acquisition and during the first trials of platform reversal and the impairment being stronger in C57BL/6 mice. In the open field, Rb mice were as active as the normal strains but showed significantly increased path tortuosity and moved slightly faster. In the extrapolation task, Rb mice showed above-chance levels in moving to the target indicated by the disappearance of the stimulus, while normal mice chose at chance levels, but the translocation effects were not statistically significant. These data indicate that telocentric fusion of chromosomes may entail behavioral alterations, perhaps by subtle changes in neurotransmitters or limbic circuitry. The expression of such alterations, however, can be remarkably strain dependent.     

Repeated acquisition of a spatial navigation task in mice: effects of spacing of trials and of unilateral middle cerebral artery occlusion

The working memory version of the Morris water escape task, the repeated acquisition task, consists of trial pairs in which an animal is started twice from the same start position. Animals have mastered this task when they need less time to find the platform in the second of the two trials. In this study, study, male C57BL mice were trained on this task with massed, spaced, or spaced delay trials in which there was a 90-min delay between the first and second trials of a pair. The mice trained with spaced trials learned the repeated acquisition task, whereas the mice trained with massed or spaced delay trials were not consistently able to do so. When the mice had reached a stable baseline performance, the middle cerebral artery (MCA) was occluded or the mice were sham-operated. Then, the effects of the MCA occlusion (MCA-O) on the performance in the repeated acquisition tasks were studied. MCA occlusion hardly affected the performance in this task, irrespective of the spacing condition of the trials, although surgery per se seemed to have a transient disruptive effect.     

The mirror chamber test for testing anxiolytics: is there a mirror-induced stimulation?

A new murine model of anxiety, namely the mirror chamber test, is based on the assumption that, like many species, mice show approach-avoidance behavior when they are confronted by a mirror. It has been suggested that the mirror chamber is a specific and a quantitatively/qualitatively different measure of anxiety than that implicated in other behavioral models such as the elevated plus-maze and the head-dipping assays. The aim of the present study was to investigate whether there was indeed a specific mirror effect by replacing the mirrors in the chamber by either white or dark-gray tiles. Balb/c, DBA-derived, and C57 BL/6j mice were tested under these three experimental conditions. The results indicated that Balb/c and DBA-derived mice avoided the mirror, white and gray chambers similarly while C57 BL/6j mice entered more readily and spent more time in the gray chamber than in the mirrored or white chambers. Thus, depending on the strain of mouse studied, a brightness or a position effect in the chamber could explain the avoidance behavior observed. These results suggest that there is no need to invoke a specific mirror effect.     

Septal lesions and behavior: Effects of presurgical rearing and strain of mouse.

In 2 experiments a total of 64 black C57BL/10J and 64 albino SJL/J male mice were reared in either enriched social cages or restricted individual cages from 25 days of age until they underwent septal or control surgery 1 mo later. Enrichment differentially altered septal or control behavior as measured by fluid consumption of water, saccharin, and quinine; performance on a rotorod; and the acquisition of an active avoidance task. The interactions of presurgical history with brain damage were manifested differently in the 2 strains of mice. The importance of attending more to genetic and presurgical history in attempts to define the effects of brain damage on behavior and to determine the function of brain structures is discussed. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rats perform better on spatial than brightness delayed matching-to-sample water-escape due to an unlearned bias to use spatial cues

Rats readily acquire water-escape spatial delayed matching-to-sample (DMTS) tasks and show excellent performance with retention intervals as long as 120 m (17). They also acquire the task more readily with a 5-min retention interval (RI) than with a 1-min RI (16). To determine if these observations are unique to spatial DMTS, or are also true of nonspatial water-escape DMTS, 75-day-old rats were compared on acquisition and subsequent retention of spatial and brightness DMTS. A larger proportion of the rats tested on the spatial problem were able to acquire the task, made fewer acquisition errors, and demonstrated better retention when tested at RIs of 1, 5, 15, 30, 60, and 120 min than did the rats tested on the brightness problem. Acquisition RI did not affect the rate of acquisition on either task. Examination of perserveration errors, the occurrence of intrusions, and position-congruent performance (escape platform in the same physical location on both runs of a trial) revealed that the choices of brightness-trained rats were often more influenced by spatial than brightness cues, suggesting that rats have an unlearned bias to use spatial cues in water-escape DMTS tasks.     

Age-related deficits in mice performing working memory tasks in a water maze.

This study determined whether mice exhibit spatial working memory deficits with increased age. C57BL/6JNia mice of 3 different ages were tested in the Morris water maze with 2 protocols designed to assess immediate and delayed working memory abilities. Young mice required multiple trials in order to show improvements in the working memory task. Deficits in immediate working memory were detected in both 10- and 24- to 26-month-old mice. Reference memory deficits and declines in performance in the delayed working memory task were only seen in 24- to 26-month-olds. This increased susceptibility of immediate working memory processes to the aging process in mice may be related to their need for more rehearsal in the water maze than other species. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Increased absolute light sensitivity in Himalayan mice with cold-induced ocular pigmentation

Controversy over the relationship between ocular pigmentation and absolute dark-adapted light sensitivity has persisted for over two decades. Previous electrophysiological experiments in hypopigmented mammals (mice, rats, rabbits) show increased thresholds in the dark-adapted state proportional to the deficit in ocular melanin. Animals with the least amount of ocular melanin have the most elevated thresholds. Dark-adapted thresholds in hypopigmented mice show similar threshold elevations in behavioral tests. The present study extends these findings to show that a specific increase in ocular pigmentation results in the converse effect, lowered absolute dark-adapted thresholds. The increase in ocular melanin was accomplished by keeping Himalayan mice in the cold (4 degrees C) for 6 weeks. Himalayan mice (C57BL/6J cH/cH) were compared to black mice (C57BL/6J (+/+)) and albino mice (C57BL/6J c2J/c2J) after 6 weeks at either 4 degrees C or 20 degrees C in 12-h cycling light (<1 cd/m2). The Himalayan mice that were kept in the cold exhibited a 44% increase in ocular melanin compared to Himalayan mice kept at room temperature. Cold rearing did not effect ocular melanin or visual thresholds in control animals (black mice = 10(-5.9) cd/m2 and albino mice = 10(-4.4) cd/m2). In contrast, the Himalayan mice maintained at 4 degrees C had thresholds of 10(-5.7) cd/m2 compared to 10(-5.1) cd/m2 for Himalayan mice kept at 20 degrees C. This represents compelling evidence of a direct relationship between ocular melanin concentration and absolute dark-adapted light sensitivity.     

Differential effects of the albino gene on behavior according to task, level of inbreeding, and genetic background.

Different generations from a Mendelian crossing schedule and 2 inbred recombinant albino strains of mice (BALB/cjOrl and C57BL/6jOrl) were compared in a water-escape and a locomotor task under dim red-orange light. Results reveal deleterious effects of the albino gene; it did not affect locomotor tasks but seriously altered cognitive capacities. The degree of expression of these effects was greater in the inbred albino Ss than in the albinos from heterozygous generations. Differences in the genetic background may also effect the degree of expression of the albino gene effects in various albino strains. The visual system is unlikely to mediate these pleiotropic effects of the albino gene. (31 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Developmental differences in place-learning performance between C57BL/6 and DBA/2 mice parallel the ontogeny of hippocampal protein kinase C.

This study determined the ontogenic changes in learning and hippocampal protein kinase C (PKC) in C57 and DBA mice. Mice were tested on the visible- or hidden-platform versions of the Morris water task starting at 17, 24, 31, or 60 days of age. Both strains learned to locate the visible platform at all ages. C57 mice learned to solve the hidden-platform task when they were 24 days old, whereas DBA mice never learned to solve this task. Using a [–3H]-phorbol ester binding assay, the authors found that both strains had similar amounts of hippocampal PKC at 10 and 17 days of age but that C57 mice had significantly more PKC at 24, 31, and 60 days of age. Immunoblotting results revealed that C57 mice had more γ-PKC, but not α-PKC, than DBA mice. Thus, the development of performance differences in spatial learning between C57 and DBA mice parallels the ontogeny of hippocampal PKC. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of anti-carrier antibody on carrier-determined tolerance

These experiments were originally designed to determine whether an anti-carrier antibody, e.g., anti-allotype could break hapten-specific tolerance in vivo. Tolerance to 2,4-dinitrophenyl (DNP) was induced in C57BL/6J mice using DNP-BALB/c IgG2a conjugate. When anti-allotype serum was injected in C57BL/6J mice one day after a single injection of DNP-IgG2a the mice were not tolerant. In contrast, when tolerance was induced by four weekly injections of tolerogen, the anti-allotype serum had no effect on the tolerant state. This effect was specific for tolerance-inducing carrier. Anti-carrier antibody injected in C57BL/6J mice one day after DNP-IgG2a produced a small but significant anti-DNP response without administration of the immunogen, whereas the tolerogen (DNP-IgG2a) by itself was not immunogenic. Similarly, despite multiple injections of DNP-IgG2a bearing the foreign allotype, only one out of 7 C57BL/6J mice showed a weak anti-carrier response. In contrast, a marked anti-carrier (IgG2a) response was obtained when the anti-allotype antibody was passively administered in C57BL/6J mice. In conclusion, these experiments suggest that tolerance to an antigenic determinant may be broken by an antibody directed not to this determinant, but to another on the same molecule. The significance of this finding in relationship to the mechanism of the carrier-determined tolerance and the breakdown of self-tolerance is discussed.     

Strain distribution of mice in discriminated Y-maze avoidance learning: Genetic and procedural differences.

The current study was conducted to characterize discriminated avoidance learning in mice by using a Y-maze task. In Experiment 1, the task parameters were manipulated, including the amount of time spent in the start arm, the amount of time to make the avoidance response, and the intertrial interval (ITI) using C57?×?SJL F1 hybrid mice. Avoidance performance was significantly improved with longer times to avoid the shock and longer ITIs. In Experiment 2, mice from 4 inbred strains (BALB/cByJ, DBA/2J, C57BL/6J, and SJL/J), an F1 hybrid (C57?×?SJL), and 1 outbred strain (CD1) were tested with various ITIs. Strain differences were observed in avoidance learning, with BALB, DBA, C57?×?SJL and CD1 mice showing significantly better avoidance learning than C57 mice, which were better than SJL mice. These data demonstrate that Y-maze performance is significantly influenced by the genetic background of the mouse and the parameters of the task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Do early-life events permanently alter behavioral and hormonal responses to stressors?

Early-life stimulation (e.g., brief handling) attenuates the behavioral and neuroendocrine responses to stressors encountered in adulthood, particularly with respect to activation of hypothalamic-pituitary-adrenal (HPA) activity. In contrast, if neonates were subjected to a more severe stressor, such as protracted separation from the dam or exposure to an endotoxin, then the adult response to a stressor was exaggerated. These early-life experiences program HPA functioning, including negative feedback derived from stimulation of hippocampal glucocorticoid receptors, and corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) coexpression in PVN neurons, to modify the response to subsequent stressor experiences. The persistent variations of HPA activity observed in handled/stimulated animals may stem from alterations in dam-pup interactions (e.g. increased arched-back feeding, licking, grooming). In addition genetic makeup is critical in determining stress reactivity. For instance, BALB/cByJ mice are more reactive to stressors than C57BL/6ByJ mice, exhibiting greater HPA hormonal alterations and behavioral disturbances. BALB/cByJ also fail to acquire a spatial learning response in a Morris water-maze paradigm, which has been shown to be correlated with hippocampal cell loss associated with aging. Early-life handling of BALB/cByJ mice prevented these performance deficits and attenuated the hypersecretion of ACTH and corticosterone elicited by stressors. The stressor reactivity may have been related to maternal and genetic factors. When BALB/cByJ mice were raised by a C57BL/6ByJ dam, the excessive stress-elicited HPA activity was reduced, as were the behavioral impairments. However, cross-fostering the more resilient C57BL/6ByJ mice to a BALB/cByJ dam failed to elicit the behavioral disturbances. It is suggested that genetic factors may influence dam-pup interactive styles and may thus proactively influence the response to subsequent stressors among vulnerable animals. In contrast, in relatively hardy animals the early-life manipulations may have less obvious effects.