The Y chromosome, social signals, and offense in mice

Offense is one type of aggression in mice (Mus musculus/Mus domesticus). Offense was measured in a panel of testers design for two congenic strains of mice. The two congenic strains were DBA1Bg and DBA1. C57BL10-YBg. These differ in the Y chromosome. Offense was measured for the following dyadic pairs: Group 1 (DBA1 tested against a DBA1 opponent); Group 2 (DBA1 tested against a DBA1.C57BL10-Y opponent); Group 3 (DBA1.C57BL10-Y tested against a DBA1.C57BL10-Y opponent); and Group 4 (DBA1.C57BL10-Y tested against a DBA1 opponent). Group 1 was more aggressive than Group 3, whereas Group 2 was no more aggressive than Group 4. Thus, when the experimental and opponent pairs have the same Y chromosome, the congenics differ in offense, whereas when the experimental and opponent pairs have different Y chromosomes, the congenics do not differ in offense. These findings are consistent with the hypothesis that these Y chromosomes affect the display of and response to social or other stimuli for offense of mice. These stimuli may be individual recognition chemosignals in urine.     

The influence of the Y-chromosome of Rb/1Bg mice on agonistic behaviors

Males of the Rb/lBg and C57BL/10Bg strains, as well as of the Bl0RblF, and RblBlOF1, reciprocal hybrids, were tested for aggression over three daily trials beginning at 50 days of age. The BlORblF, hybrids were sired by Rb/lBg males, and the RblBlOF, hybrids were sired by C57BL/10Bg males. The mean scores for the agonistic acts of chase, wrestle, flank-bite (but not tail rattle or attack), and the mean “aggression” score (but not mean latencies to first agonistic act or first attack) were significantly higher for BlORblF, than for RblBlOF, hybrids. These findings are consistent with the hypothesis that some aspect(s) of the Rb/lBg Y-chromosome strain can influence the occurrence of some of the motor patterns of offense but not defense. The Y-chromosomes of the DBA/1, DBA/2, CBA, and PHH inbred strains have a similar effect on agonistic behaviors.     

Effects of the heterosomes and maternal environments on aggressive behavior in Mus musculus

This is a study of the offense type of aggression in males of the DBA/1Bg and C57BL/10Bg inbred strains of mice and their two reciprocal F1 hybrids. It uses three test paradigms for dyadic encounters: the homogeneous set test, an identity panel of testers, and the standard opponent test. There were no reciprocal F1 hybrid differences for any of the 12 behavioral measures of aggression in the homogeneous set test or the standard opponent test. For the panel of testers paradigm, reciprocal F1 hybrid differences occurred when the tester (opponent) was an F1 hybrid male, but not when the tester (opponent) was an RB/1 or C57BL10 male. When B10RB1F1 males were the testers (opponents), B10RB1F1 hybrid males were more aggressive than RB1B10F1 hybrid males across 10 of the 12 behavioral measures. Conversely, when RB1B10F1 males were the testers (opponents), RB1B10F1 males were more aggressive than B10RB1F1 males across 9 of the 12 behavioral measures. These results conform to the following empirical rule: A significant difference between reciprocal F1 hybrids is observed for these behavioral measures when one of the hybrids has both of its heterosomes (X and Y chromosomes) and its maternal environment identical to those of its opponent and the other hybrid has none of these identical to those of its opponent. These results are consistent with a model in which on some genetic backgrounds, but not on others, similarity of the heterosomes and maternal environments can influence the display of or response to social or other stimuli for the offense type of aggression in mice. These stimuli may be individual recognition chemosignals in urine.     

Strain-dependent interactions between MK-801 and cocaine on retention of C57BL/6 and DBA/2 mice tested in a one-trial inhibitory avoidance task: involvement of dopaminergic mechanisms

Two sets of experiments were carried out with C57BL/6 (C57) and DBA/2 (DBA) mice tested in a one-trial inhibitory avoidance task. In the first set C57 and DBA mice were injected posttraining with saline or with the D1 DA receptor antagonist SCH 23390 and then with saline, cocaine (5 mg/kg), MK-801 (0.1 mg/kg), or with a combination of these two drugs. Cocaine enhanced retention in the C57 strain and impaired it in the DBA strain, and MK-801 potentiated the effects of cocaine in both strains. Furthermore, pretreatment with SCH 23390 completely antagonized the potentiation of the effects of cocaine exerted by MK-801. In the second set of experiments mice belonging to these same two strains were injected posttraining with vehicle or with the D2 DA receptor antagonist (-)-sulpiride and then with saline, cocaine (5 mg/kg), MK-801 (0.1 mg/kg), or with a combination of these two drugs. Pretreatment with the D2 DA receptor antagonist completely antagonized in both strains the potentiation of the effect of cocaine exerted by MK-801. The results of the present research show that the noncompetitive NMDA receptor antagonist MK-801 enhances the effect of cocaine on retention performance in C57 and DBA mice and that dopaminergic mechanisms are involved in this potentiation.     

Strain and sex differences on olfactory discrimination learning in C57BL/6J and DBA/2J inbred mice (Mus musculus)

In this study, the authors explored potential strain and sex differences in nonspatial cognitive ability. Beginning around 90 days of age, male and female C57BL/6J (C57) and DBA/2J (DBA) inbred mice (Mus musculus) were tested on a task of simple odor discrimination learning with 3 repeated reversals. Males learned the task more readily than females, and DBA mice learned the task more readily than C57 mice. All differences became evident after repeated testing. Similarity of perseveration measures indicated the differences were not due to inhibitory deficits. Instead, a phase analysis localized differences to a transitional period of reversal learning. Females increased transitional errors that more likely indicated adaptive sampling strategies than memory failures. C57 females used this strategy indiscriminately, but DBA females sampled as a function of environmental uncertainty.     

Studies on wild house mice VI: Differential effects of the Y chromosome on intermale aggression

The aim of this study is to determine the effects of different parts of the Y chromosome of wild house mice on aggression. To reach this goal, intercrosses were made between two selection lines for attack latency (SAL and LAL) and their congenic strains (SAL. LY and LAL. SY). This procedure resulted in F₁ hybrids that carried the same autosomes, but differed in their X chromosome and the two different parts of their Y chromosomes, the different parts of the Y chromosome being a recombining part called the pseudoautosomal region (PAR) and a non-recombining part (non-PAR). We conclude that both parts of the Y chromosome contribute slightly but significantly to variation in aggression. The major effect is accomplished by the PAR of the aggressive parent; a mirror effect is achieved by the non-PAR of the aggressive parent in interaction with the PAR. © 1994 Wiley-Liss, Inc.     

Learning strategy selection in the water maze and hippocampal CREB phosphorylation differ in two inbred strains of mice

Learning strategy selection was assessed in two different inbred strains of mice, C57BL/6 and DBA/2, which are used for developing genetically modified mouse models. Male mice received a training protocol in a water maze using alternating blocks of visible and hidden platform trials, during which mice escaped to a single location. After training, mice were required to choose between the spatial location where the platform had been during training (a place strategy) and a visible platform presented in a new location (a cued/response strategy). Both strains of mice had similar escape performance on the visible and hidden platform trials during training. However, in the strategy preference test, C57BL/6 mice selected a place strategy significantly more often than DBA/2 mice. Because much evidence implicates the hippocampus and striatum as important neural substrates for spatial/place and cued/response learning, respectively, the engagement of the hippocampus was then assessed after either place or cue training by determining levels of cAMP response element-binding protein (CREB) and phosphorylated CREB (pCREB) in these two mouse strains. Results revealed that hippocampal CREB levels in both strains of mice were significantly increased after place in comparison to cued training. However, the relation of hippocampal pCREB levels to training was strain dependent; pCREB was significantly higher in C57BL/6 mice than in DBA/2 mice after place training, while hippocampal pCREB levels did not differ between strains after cued training. These findings indicate that pCREB, specifically associated with place/spatial training, is closely tied to differences in spatial/place strategy preference between C57BL/6 and DBA/2 mice.     

Genetic differences in the mouse defense test battery

The mouse defense test battery (MDTB) has been designed to examine anxiogenic- or anxiolytic-like properties of psychoactive drugs through effects on specific defensive behaviors. In the present study, the MDTB was used to evaluate the potential contribution of genetic factors to these behaviors. The data revealed pronounced differences in several defense reactions among four inbred strains (BALB/c, C57BL/6, CBA, DBA/2) and one outbred (Swiss) mouse line. Thus, when subjects were introduced into the apparatus, Swiss and C57BL/6 displayed the highest levels of horizontal and vertical activities, while BALB/c and DBA/2 mice showed intermediate and CBA low activity rates. When subjects were chased by the rat, C57BL/6 mice used flight as the dominant defense strategy, while the defensive responses of BALB/c, C57BL/6, and DBA/2 mice consisted of flight reactions and risk assessment activities. However, when flight or escape was not possible, risk assessment became the predominant feature of the defense repertoire in the C57BL/6 mice. When defensive threat/attack behaviors were required, Swiss, BALB/c, DBA/2, and C57BL/6 mice showed very similar reactions in terms of the magnitude of the responses observed. CBA mice were poorly defensive in all these test situations. Finally, after the rat was removed from the test apparatus, Swiss, DBA/2, and C57BL/6 mice displayed more vertical activities than BALB/c mice. These latter, however, showed an increased level of ambulation compared to the activity recorded before the rat exposure. Together, these findings indicate that genetic factors contribute to defensive behaviors in this animal model of anxiety. The different behavioral profiles displayed by the strains used here may provide the means to obtain a better insight into the neurobehavioral mechanisms involved in anxiety-related disorders. Aggr. Behav. 23:19–31, 1997. © 1997 Wiley-Liss, Inc.     

Strain-dependent differences in LTP and hippocampus-dependent memory in inbred mice

Many studies have used "reverse" genetics to produce "knock-out" and transgenic mice to explore the roles of various molecules in long-term potentiation (LTP) and spatial memory. The existence of a variety of inbred strains of mice provides an additional way of exploring the genetic bases of learning and memory. We examined behavioral memory and LTP expression in area CA1 of hippocampal slices prepared from four different inbred strains of mice: C57BL/6J, CBA/J, DBA/2J, and 129/SvEms-+(Ter?)/J. We found that LTP induced by four 100-Hz trains of stimulation was robust and long-lasting in C57BL/6J and DBA/2J mice but decayed in CBA/J and 129/SvEms-+(Ter?)/J mice. LTP induced by one 100-Hz train was significantly smaller after 1 hr in the 129/SvEms-+(Ter?)/J mice than in the other three strains. Theta-burst LTP was shorter lasting in CBA/J, DBA/2J, and 129/SvEms-+(Ter?)/J mice than in C57BL/6J mice. We also observed specific memory deficits, among particular mouse strains, in spatial and nonspatial tests of hippocampus-dependent memory. CBA/J mice showed defective learning in the Morris water maze, and both DBA/2J and CBA/J strains displayed deficient long-term memory in contextual and cued fear conditioning tests. Our findings provide strong support for a genetic basis for some forms of synaptic plasticity that are linked to behavioral long-term memory and suggest that genetic background can influence the electrophysiological and behavioral phenotypes observed in genetically modified mice generated for elucidating the molecular bases of learning, memory, and LTP.     

Aggressive behavior in inbred strains of mice during pregnancy

Female aggressive behavior toward adult male ICR/JCl mice was compared for virgin and pregnant mice of five inbred strains (BALB/c, C3H/He, C57BL/6, DBA/2J, and AKR/J). Pregnant females from four strains except BALB exhibited intense aggressive behavior, whereas only virgin AKR females were aggressive. Aggressive behavior began in early pregnancy, was highest in midpregnancy, and declined slightly thereafter until the day of parturition. The level of aggressive behavior showed significant strain differences. The topography of aggressive behavior was also different among the four strains. DBA females showed marked contrast with the other three strains in the temporal changes of aggression in the first phase of encounter. Furthermore, strain specific behavioral pattern of aggression was demonstrated based on six behavioral acts ( Darting , Chasing, Attack, Biting, Wrestling, and Boxing). Virgin and pregnant AKR females showed the identical behavioral pattern of aggression.     

Selective improvement of strain-dependent performances of cognitive tasks by food restriction

Temporary food restriction affects strain differences for behavioral phenotypes in the inbred strains of mice C57BL/6 (C57) and DBA/2 (DBA). Since food restriction is a routine procedure to motivate learning, we evaluated its influence on differences for spatial and non-spatial discrimination between these strains of mice by using two non-associative tasks: the Spatial Novelty Test (SNT) and the Spontaneous Object Recognition Test (SORT). The results confirmed the poor performance of the DBA mice in SNT. Nonetheless, DBA mice were perfectly able to recognize the novel object in SORT. By contrast, C57 mice were good performers in SNT but failed to recognize a novel object in SORT. Finally, food restriction selectively improved C57 performance in SNT and DBA performance in SORT. These results support the view that a food restricting procedure enhances strain differences for discrimination of configurational information.     

Anxiety and maternal aggression in house mice (Mus musculus): a look at interindividual variability

The hypotheses were tested that mouse motherhood is accompanied by decreased reactivity to aversive stimuli and that female anxiety is inversely related to the probability of displaying intense forms of postpartum aggression. Outbred Swiss female mice were tested for anxiety in a light/dark choice test when virgin, pregnant, or lactating, and then tested for maternal aggression (5-min exposure to a male intruder) on postpartum Day 7. Anxiety declined in pregnant and lactating females when compared with virgin animals. Furthermore, females who displayed higher scores of postpartum fighting were less anxious in the previous test regardless of reproductive stage. Part of interindividual variability in postpartum aggression might thus be related to differences in the extent to which individuals perceive and react to anxiogenic situations. In addition, the higher emotionality characterizing the C57BL/6 and DBA/2 inbred strains may be responsible for the lack of a clear-cut exhibition of maternal aggression in these two strains.     

Landmark-based but not vestibular-based orientation elicits mossy fiber synaptogenesis in the mouse hippocampus

This study tries to shed light on the paradoxical finding that two inbred strains of mice C57BL/6 (C57) and DBA/2 (DBA), with differences in hippocampal function, perform similarly in the water maze (WM). Mice from both strains were trained on WM protocols permitting or preventing the use of vestibular signals. Hippocampal involvement in performance was then assessed by estimation of post-training mossy fiber (MF) synaptogenesis. We found that C57 and DBA mice performed similarly when both visual and vestibular information were available but only C57 mice exhibited new MF synapses. Disruption of vestibular inputs impaired performance in DBA mice but not in C57 mice which still exhibited a post-training increase of hippocampal MF synaptic terminals. This strain-specific dissociation indicates that DBA mice can navigate successfully by relying on vestibular signals without engaging their hippocampus. In contrast, vestibular signals are irrelevant for C57 mice since their suppression neither disrupts their behavior nor prevents the formation of new hippocampal synapses. These findings suggest some caution is required in considering performance on standard WM protocols as an index of hippocampus-based learning. Estimating the extent of post-training mossy fiber synaptogenesis would be helpful in solving this issue.     

Voluntary selection of and tolerance to 1,2 propanediol (propylene glycol) by high and low ethanol-selecting mouse strains.

Fifteen male mice from each of 4 inbred strains (C57BL/6J, BALB/cJ, CBA/J, and DBA/2J) were tested to determine their voluntary self-selection of a 10% solution of 1,2 propanediol (1,2 PD), A 3-carbon alcohol of low toxicity. As with ethanol, the C57BL/6J strain consumed significantly greater amounts that the 3 other low ethanol-selecting strains. A second experiment determined that the 3 low selecting strains suffered significantly greater depression of the central nervous system from 1,2 PD than the high selecting C57BL strain. It was also found that ethanol is a much more potent depressant that 1,2 PD. These results are discussed in terms of the possible role of neural sensitivity in regulating consumption levels of the 2 alcohols.     

Comparison between BALB/cJ and BALB/cByJ mice in tests of social behavior and resident-intruder aggression

The behavior of male mice from two BALB strains, the BALB/cJ strain and the BALB/cByJ strain, was examined with a social behavior test and a resident-intruder paradigm. Prior to testing, the animals were isolated for 0, 2, 5, or 10 days. In the social behavior test the pairs of BALB/cJ mice spent more time in active social interaction than pairs of BALB/cByJ mice, although the latter strain showed more locomotor activity. BALB/cJ mice isolated for 5–10 days, when tested in a familiar environment were more aggressive than mice from the BALB/cByJ strain. In the resident-intruder paradigm, in which a resident BALB mouse was confronted with an intruder NIH Swiss mouse, the BALB/cByJ mice showed more social investigation in their home cage towards the intruders, but there were no significant differences between the two strains in the amounts of aggressive behavior exhibited. The results of these experiments suggest that there are some differences in the social behavior of the genetically related BALB/cJ and BALB/cByJ mice. However, the differences appear subtle and paradigm-specific.     

The influence of visual ability on learning and memory performance in 13 strains of mice

We calculated visual ability in 13 strains of mice (129SI/Sv1mJ, A/J, AKR/J, BALB/cByJ, C3H/HeJ, C57BL/6J, CAST/EiJ, DBA/2J, FVB/NJ, MOLF/EiJ, SJL/J, SM/J, and SPRET/EiJ) on visual detection, pattern discrimination, and visual acuity and tested these and other mice of the same strains in a behavioral test battery that evaluated visuo-spatial learning and memory, conditioned odor preference, and motor learning. Strain differences in visual acuity accounted for a significant proportion of the variance between strains in measures of learning and memory in the Morris water maze. Strain differences in motor learning performance were not influenced by visual ability. Conditioned odor preference was enhanced in mice with visual defects. These results indicate that visual ability must be accounted for when testing for strain differences in learning and memory in mice because differences in performance in many tasks may be due to visual deficits rather than differences in higher order cognitive functions. These results have significant implications for the search for the neural and genetic basis of learning and memory in mice.     

Genotype modulates prenatal stress effects on aggression in male and female mice

Prenatal stress (heat and restraint) significantly increased postpartum aggression (proportion of animals fighting and/or the intensity of the behavior) in C57BL/6J female mice and reduced the behavior in DBA/2J females. For intermale aggression, prenatal stress increased the behavior (intensity of aggression) in C57BL/6J males but did not affect aggressive behavior in DBA/2J animals. Infanticidal behavior (the killing of young) exhibited by male mice was not influenced by prenatal stress in either strain. Relative anogenital distance measurements in neonates at birth did not serve as a reliable predictor of strain variation in prenatal stress effects. Prenatal stress did not influence this measure of prenatal androgen exposure in DBA/2J or C57BL/6J females. For males, prenatal stress elevated relative anogenital distance in C57BL/6J mice and decreased this measure in DBA/2J animals. Prenatal stress effects on aggressive behavior in male and female mice therefore depend upon genotype. Strain-dependent differences may be modulated by differences in endocrine reactivity to prenatal stress/and or differential central neural tissue sensitivity to hormones.     

Place avoidance learning and stress-induced analgesia in the attacked mouse: role of endogenous opioids

In this study, mechanisms of pain inhibition (tail-flick test) and memory (place avoidance paradigm) were investigated in attacked, DBA/2 and C57BL/6, mice. During training, exposure of test animals to 10 or 30 bites by an aggressive, isolated ICR mouse situated in the dark half of a bright/dark conditioning box induced a significantly higher social conflict analgesia in DBA than in C57 mice. Naltrexone (0.5 and 2.0 mg/kg) reduced this response in DBA mice that received 30, but not 10, bites and was ineffective in C57 mice. This points to different, opioid versus naltrexone-insensitive nonopioid, analgesic mechanisms. During place choice testing in the same box 24 h later, DBA mice that had received 30, but not 10, bites showed a significant, naltrexone-reversible, avoidance of the attack place. No place avoidance learning was observed in C57 mice. The data provided unequivocal evidence that place avoidance learning was a result of associative conditioning, in that neither pairing nor social conflict per se significantly changed the preference for the dark side seen in experimentally naive DBA mice. Antagonism of place avoidance conditioning was observed regardless of whether testing was carried out in the drugged or undrugged state, excluding possible state-dependent effects as an explanation for the naltrexone-induced impairment. Individual correlational analysis in saline-injected, attacked DBA mice revealed a negative relationship between the analgesic state immediately after training and the avoidance of attack place during testing. In summary, the results suggest strain-dependent analgesic and learning mechanisms and indicate that endogenous opioids released in attacked DBA mice support pain inhibition and modulate the memorization of attack place by their analgesic effects, as well as by mechanisms independent of pain inhibitory systems.     

Opposite strain-dependent differences for intermale aggressive behavior elicited by individual housing and housing with a female in the mouse

Male mice of the C57BL/6 strain show a significant increase in aggression toward a nonaggressive male conspecific following 72 hr of individual housing. However, this increase was no longer evident following 2 weeks of individual housing. When housed with a female, C57BL/6 mice show significantly more aggression than singly housed mice of the same strain after 72 hr as well as 2, 4, 8 weeks of differential housing. Male C57BL/6 mice housed with a female also show significantly higher levels of aggression than DBA/2 mice living in the same housing condition after 4 or 8 weeks of differential housing. Finally, male DBA/2 mice individually housed for 8 weeks are significantly more aggressive than mice of the same strain housed with a female for the same time. These results indicate that the increase in aggressive behavior observed following isolation and cohabitation with a female in the mouse is not the same phenomenon. © 1994 Wiley-Liss, Inc.     

Derived manding in children with autism: synthesizing Skinner's verbal behavior with relational frame theory

Mand functions for two stimuli (A1 and A2) were trained for 3 children with autism and were then incorporated into two related conditional discriminations (A1-B1/A2 -B2 and B1-C1/B2-C2). Tests were conducted to probe for a derived transfer of mand response functions from A1 and A2 to C1 and C2, respectively. When 1 participant failed to demonstrate derived transfer of mand response functions, transfer training using exemplars was conducted. When participants had demonstrated derived transfer of mand functions, the X1 and X2 tokens that were employed as reinforcers for mand responses were incorporated into two conditional discriminations (X1-Y1/X2-Y2 and Y1-Z1/Y2-Z2). Tests were conducted for derived transfer of reinforcing functions. Finally, tests were conducted to determine if the participants would demonstrate derived manding for the derived reinforcers (present C1 and C2 to mand for Z1 and Z2, respectively). Derived transfer of functions was observed when the sequence of training and testing was reversed (i.e., training and testing reinforcing functions before mand response functions) and when only minimal instructions were provided.