Isabelle Girard

Exercise Increases Hippocampal Neurogenesis to High Levels but Does Not Improve Spatial Learning in Mice Bred for Increased Voluntary Wheel Running

The hippocampus is important for the acquisition of new memories. It is also one of the few regions in the adult mammalian brain that can generate new nerve cells. The authors tested the hypothesis that voluntary exercise increases neurogenesis and enhances spatial learning in mice selectively bred for high levels of wheel running (S mice). Female S mice and outbred control (C) mice were housed with and without running wheels for 40 days. 5-Bromodeoxyuridine was used to label dividing cells. The Morris water maze was used to measure spatial learning. C runners showed a strong positive correlation between running distance and new cell number, as well as improved learning. In S runners, neurogenesis increased to high levels that reached a plateau, but no improvement in learning occurred. This is the first evidence that neurogenesis can occur without learning enhancement. The authors propose an alternative function of neurogenesis in the control of motor behavior.

Locomotor performance and social dominance in male Anolis cristatellus

The proximal mechanisms determining social dominance are not well understood. We used the highly territorial lizard A. cristatellus to test two main hypotheses: (1) that male social dominance is associated with locomotor abilities; (2) that locomotor abilities (maximal performance), as measured in the laboratory, are correlated with behaviour in the field. In the field, we recorded locomotor behaviours and assertion displays, then characterized microhabitat use and thermal relations. In the laboratory, we measured maximum sprint running speed, endurance and morphometric characters, and assessed dominance by pairing males of similar body size in an experimental arena. In 72 of 77 interactions, one lizard (the ‘winner’) was unequivocally determined to be dominant over the other (the ‘loser’). Winners performed more assertion displays than losers before capture and also had higher endurance in laboratory tests. Although contestants were matched for snout–vent length, winners had significantly deeper and wider heads. However, we found no significant differences in field locomotor behaviours, perch or thermal characteristics, head length, or maximal sprint speed. Our findings support those of previous studies, and extend them in several ways. This is the first demonstration that assertion displays in the field are related to both locomotor performance and laboratory-assessed social dominance. Locomotor performance may directly affect social dominance by allowing some males to perform better in dyadic interactions. Alternatively, both locomotor performance and social dominance may be linked to a common underlying mechanism, such as variation in hormone levels, which are known to affect aggression, locomotor performance and morphology.

Evolution of a small-muscle polymorphism in lines of house mice selected for high activity levels.

Abstract To study the correlated evolution of locomotor behavior and exercise physiology, we conducted an artificial selection experiment. From the outbred Hsd:ICR strain of Mus domesticus, we began eight separate lines, each consisting of 10 breeding pairs. In four of the lines, we used within‐family selection to increase voluntary wheel running. The remaining four lines were random‐bred (within lines) to serve as controls. Various traits have been monitored to test for correlated responses. Here, we report on organ masses, with emphasis on the triceps surae muscle complex, an important extensor of the ankle. Mice from the selected lines exhibit reduced total body mass, increased relative (mass‐corrected) kidney mass, and reduced relative triceps surae mass. In addition, a discrete muscle‐mass polymorphism was observed: some individuals had triceps surae that were almost 50% lighter than normal for their body mass. This small‐muscle phenotype was observed in only three of the eight lines: in one control line, it has fluctuated in frequency between zero and 10%, whereas in two of the selected lines it has increased in frequency to approximately 50% by generation 22. Data from a set of parents and offspring (generations 23 and 24) are consistent with inheritance as a single autosomal recessive allele. Evidence for the adaptive significance of the small‐muscle allele was obtained by fitting multiple‐generation data to hierarchical models that include effects of genetic drift and/or selection. The small‐muscle allele is estimated to have been present at low frequency (approximately 7%) in the base population, and analysis indicates that strong selection favors the allele in the selected but not control lines. We hypothesize that the small muscles possess functional characteristics and/or that the underlying allele causes pleiotropic effects (e.g., reduced total body mass; increased relative heart, liver, and kidney mass) that facilitate high levels of wheel running. Nevertheless, at generation 22, wheel running of affected individuals did not differ significantly from those with normal‐sized muscles, and the magnitude of response to selection has been similar in all four selected lines, indicating that multiple genetic “solution” are possible in response to selection for high activity levels.

Open-Field Behavior of House Mice Selectively Bred for High Voluntary Wheel-Running

Open-field behavioral assays are commonly used to test both locomotor activity and emotionality in rodents. We performed open-field tests on house mice (Mus domesticus) from four replicate lines genetically selected for high voluntary wheel-running for 22 generations and from four replicate random-bred control lines. Individual mice were recorded by video camera for 3 min in a 1-m2 open-field arena on 2 consecutive days. Mice from selected lines showed no statistical differences from control mice with respect to distance traveled, defecation, time spent in the interior, or average distance from the center of the arena during the trial. Thus, we found little evidence that open-field behavior, as traditionally defined, is genetically correlated with wheel-running behavior. This result is a useful converse test of classical studies that report no increased wheel-running in mice selected for increased open-field activity. However, mice from selected lines turned less in their travel paths than did control-line mice, and females from selected lines had slower travel times (longer latencies) to reach the wall. We discuss these results in the context of the historical open-field test and newly defined measures of open-field activity.

Predatory aggression, but not maternal or intermale aggression, is associated with high voluntary wheel-running behavior in mice

Predatory (towards crickets), intermale, and maternal aggression were examined in four replicate lines of mice that had been selectively bred for high wheel-running (S) and in four random-bred control lines (C). In generation 18, individual differences in both predatory and intermale aggression were significantly consistent across four trial days, but predatory and intermale aggression were uncorrelated both at the individual level and among the eight line means. Latencies to attack crickets were significantly lower in S lines as a group. Intermale aggression, however, did not differ between S and C lines. S lines were significantly smaller in body mass, but did not differ in either testes mass or plasma testosterone. In generations 28 and 30, respectively, S and C lines did not differ in either maternal or intermale aggression. However, significant differences among the individual lines were found for maternal aggression, and one S line exhibited an extremely high mean time of aggression (>120 sec for a 5-min test). Maternal and intermale aggression were not correlated among the eight line means or at the level of individual variation. Overall, our results suggest: (1) predatory aggression and voluntary wheel-running are positively related at the genetic level; (2) predatory and intermale aggression are unrelated at a genetic level; and (3) maternal and intermale aggression are not tightly related at the genetic level. Possible relationships between predatory aggression, dopamine, and wheel-running behavior are discussed.

Leptin Levels and Body Composition of Mice Selectively Bred for High Voluntary Locomotor Activity

Selective breeding produced four replicate lines of high‐runner (HR) mice that run on wheels for approximately 2.7 times more revolutions per day than four unselected control lines. Previous studies found that HR mice of both sexes have lower body fat (isotope dilution at 15 wk of age) and that males (females not studied) have smaller retroperitoneal fat pads (17 wk). HR mice also exhibit elevated plasma corticosterone and insulin‐stimulated glucose uptake by some hindlimb muscles but apparently do not differ in circulating insulin or glucose levels (males at 18 wk). Given their lower body fat and higher activity levels, we hypothesized that HR mice would have lower circulating leptin levels than controls. Female mice were given wheel access for 6 d at 7 wk of age, as part of the routine wheel testing for the selective breeding protocol, and then were killed after one additional week without wheels to reduce possible acute effects of activity on leptin. As hypothesized, serum leptin levels were significantly lower in HR mice. ANCOVA indicated that leptin was strongly positively correlated with both total body fat (measured by ether extraction) and body mass change from weaning, but HR mice still had significantly lower adjusted leptin levels (ANCOVA). Within HR lines but not within control lines, individual variation in leptin levels was negatively correlated with amount or speed of wheel running measured a week before being killed. Growth from weaning to euthanasia and body dry mass were lower in HR mice than in controls, but absolute dry masses of the ventricles, liver, gut, and uterus plus ovaries did not significantly differ, nor did percentage of the total dry mass as fat. HR mice offer a novel model for studying the causes and consequences of physiologically relevant variations in serum leptin.

Maternal-care behavior and life-history traits in house mice (Mus domesticus) artificially selected for high voluntary wheel-running activity

To test the hypothesis that selective breeding for high voluntary wheel running negatively affects maternal performance in house mice, we observed maternal behavior and compared litter size and mass, in replicate lines of selected (N=4) and control (N=4) mice from generations 20 and 21 of an artificial selection experiment. At generation 21, selected-line females ran 2.8-times more revolutions per day than females from random-bred control lines, when tested at approximately 6 weeks of age as part of the normal selection protocol. After giving birth, dams from selected and control lines exhibited similar frequencies of maternal behaviors and also spent similar amounts of time in general locomotor activity at litter ages of both 9 and 16 days. Dams from selected lines also performed equally well as controls in repeated pup-retrieval trials. At first parturition, selected-line dams averaged 2.4 g smaller in body mass as compared with dams from the control lines; however, neither litter size nor litter mass at birth (generation 20) or at weaning (generation 21) differed significantly between selected and control lines. We conclude that, at least under the husbandry conditions employed, maternal behavior and reproductive output at first parturition are genetically independent of wheel-running behavior.

Opioid-mediated pain sensitivity in mice bred for high voluntary wheel running

We tested the hypothesis that thermal tail-flick latency, a common measure of pain sensitivity in rodents, would be altered in lines of mice that had been selectively bred for high voluntary wheel-running behavior. Specifically, we predicted that the selected (High-Runner) lines would show decreased pain sensitivity relative to their control (C; randombred) lines, and would respond differently to drugs that block opioid receptors. We first compared tail-flick latency between High-Runner and C female mice during the day (no wheel access) and at night (with wheel access). Second, we compared effects of the opioid antagonist naloxone (10 mg/kg, i.p.) on tail-flick latency during the day (no wheel access). Third, we compared effects of naloxone (5 and 10 mg/kg, i.p.) and naltrexone, a longer-lasting opioid antagonist (0.1, 1, 5, 10, 50, and 100 mg/kg, i.p.), on voluntary wheel running. Tail-flick latencies were longer at night (when mice were active on wheels), but mice from High-Runner and C lines did not differ during the day or night. Administration of naloxone (10 mg/kg, i.p.) decreased tail-flick latency measured during the day, equally in High-Runner and C mice. Naloxone (5 and 10 mg/kg, i.p.) and high doses of naltrexone (50 and 100 mg/kg, i.p.) decreased wheel running equally in High-Runner and C mice. Further studies will be required to determine whether other types of pain sensitivity have also failed to evolve in association with increased voluntary wheel running.

Field cost of activity in the kit fox, Vulpes macrotis.

Field metabolic rates and daily movement distances were measured in 26 individual kit foxes (Vulpes macrotis) over a 29‐mo period in the southern Mojave Desert of California. Kit foxes traveled long distances (up to 32 km d−1), with males usually traveling farther than females. Daily movement distances were affected by season, since males traveled the greatest distances in spring and females traveled farthest in summer. Individual foxes tracked multiple times demonstrated repeatability of daily movement distance between nights, between summer and winter, and between consecutive winters. The field cost of activity per unit distance was estimated as 15.6 kJ km−1 from the partial regression coefficient of a multiple linear regression model, a value not significantly different from the incremental cost of locomotion derived from laboratory measurements. The field cost of activity was not affected by season, despite the expectation of higher costs of activity in the winter with increased thermoregulatory expenditure. The large daily movement distances resulted in significant activity energy expenditure (11%–33% of field metabolic rate), with a mean of 21% of field metabolic rate expended in activity during nonreproductive seasons.