Effects of voluntary activity and genetic selection on muscle metabolic capacities in house mice Mus domesticus.

Selective breeding is an important tool in behavioral genetics and evolutionary physiology, but it has rarely been applied to the study of exercise physiology. We are using artificial selection for increased wheel-running behavior to study the correlated evolution of locomotor activity and physiological determinants of exercise capacity in house mice. We studied enzyme activities and their response to voluntary wheel running in mixed hindlimb muscles of mice from generation 14, at which time individuals from selected lines ran more than twice as many revolutions per day as those from control (unselected) lines. Beginning at weaning and for 8 wk, we housed mice from each of four replicate selected lines and four replicate control lines with access to wheels that were free to rotate (wheel-access group) or locked (sedentary group). Among sedentary animals, mice from selected lines did not exhibit a general increase in aerobic capacities: no mitochondrial [except pyruvate dehydrogenase (PDH)] or glycolytic enzyme activity was significantly (P < 0.05) higher than in control mice. Sedentary mice from the selected lines exhibited a trend for higher muscle aerobic capacities, as indicated by higher levels of mitochondrial (cytochrome-c oxidase, carnitine palmitoyltransferase, citrate synthase, and PDH) and glycolytic (hexokinase and phosphofructokinase) enzymes, with concomitant lower anaerobic capacities, as indicated by lactate dehydrogenase (especially in male mice). Consistent with previous studies of endurance training in rats via voluntary wheel running or forced treadmill exercise, cytochrome-c oxidase, citrate synthase, and carnitine palmitoyltransferase activity increased in the wheel-access groups for both genders; hexokinase also increased in both genders. Some enzymes showed gender-specific responses: PDH and lactate dehydrogenase increased in wheel-access male but not female mice, and glycogen phosphorylase decreased in female but not in male mice. Two-way analysis of covariance revealed significant interactions between line type and activity group; for several enzymes, activities showed greater changes in mice from selected lines, presumably because such mice ran more revolutions per day and at greater velocities. Thus genetic selection for increased voluntary wheel running did not reduce the capability of muscle aerobic capacity to respond to training.     

Genetic selection of mice for high voluntary wheel running: effect on skeletal muscle glucose uptake.

Effects of genetic selection for high wheel-running activity (17th generation) and access to running wheels on skeletal muscle glucose uptake were studied in mice with the following treatments for 8 wk: 1) access to unlocked wheels; 2) same as 1, but wheels locked 48 h before glucose uptake measurement; or 3) wheels always locked. Selected mice ran more than random-bred (nonselected) mice (8-wk mean +/- SE = 8,243 +/- 711 vs. 3,719 +/- 233 revolutions/day). Body weight was 5-13% lower for selected vs. nonselected groups. Fat pad/body weight was ~40% lower for selected vs. nonselected and unlocked vs. locked groups. Insulin-stimulated glucose uptake and fat pad/body weight were inversely correlated for isolated soleus (r = -0.333; P < 0.005) but not extensor digitorum longus (EDL) or epitrochlearis muscles. Insulin-stimulated glucose uptake was higher in EDL (P < 0.02) for selected vs. nonselected mice. Glucose uptake did not differ by wheel group, and amount of running did not correlate with glucose uptake for any muscle. Wheel running by mice did not enhance subsequent glucose uptake by isolated muscles.     

Artificial selection for high activity favors mighty mini-muscles in house mice

After 14 generations of selection for voluntary wheel running, mice from the four replicate selected lines ran, on average, twice as many revolutions per day as those from the four unselected control lines. To examine whether the selected lines followed distinct strategies in the correlated responses of the size and metabolic capacities of the hindlimb muscles, we examined mice from selected lines, housed for 8 wk in cages with access to running wheels that were either free to rotate ("wheel access" group) or locked ("sedentary"). Thirteen of twenty individuals in one selected line (line 6) and two of twenty in another (line 3) showed a marked reduction ( approximately 50%) in total hindlimb muscle mass, consistent with the previously described expression of a small-muscle phenotype. Individuals with these "mini-muscles" were not significantly smaller in total body mass compared with line-mates with normal-sized muscles. Access to free wheels did not affect the relative mass of the mini-muscles, but did result in typical mammalian training effects for mitochondrial enzyme activities. Individuals with mini-muscles showed a higher mass-specific muscle aerobic capacity as revealed by the maximal in vitro rates of citrate synthase and cytochrome c oxidase. Moreover, these mice showed the highest activities of hexokinase and carnitine palmitoyl transferase. Females with mini-muscles showed the highest levels of phosphofructokinase, and males with mini-muscles the highest levels of pyruvate dehydrogenase. As shown by total muscle enzyme contents, the increase in mass-specific aerobic capacity almost completely compensated for the reduction caused by the "loss" of muscle mass. Moreover, the mini-muscle mice exhibited the lowest contents of lactate dehydrogenase and glycogen phosphorylase. Interestingly, metabolic capacities of mini-muscled mice resemble those of muscles after endurance training. Overall, our results demonstrate that during selection for voluntary wheel running, distinct adaptive paths that differentially exploit the genetic variation in morphological and physiological traits have been followed.     

Food consumption and body composition in mice selected for high wheel-running activity

The effects of genetic selection for high wheel running (13th generation) and prolonged access (8 weeks) to running wheels on food consumption and body composition were studied in house mice (Mus domesticus). Mice from four replicate lines selected for high wheel-running activity ran over twice as many revolutions per day on activity wheels as did mice from four replicate control lines. At approximately 49 days of age, all mice were placed individually in cages with access to wheels and monitored for 6 days, after which wheels were prevented from rotating for the "sedentary" individuals. During the experiment, five feeding trials were conducted and body mass was measured weekly. After 8 weeks, body composition was measured by hydrogen isotope dilution. Across the five feeding trials, mice in the "active" group (wheels free to rotate) consumed 22.4% more food than mice in the "sedentary" group (wheels locked); mice from the selected lines consumed 8.4% more food than mice from the control lines (average of all trials; body mass-corrected values). In females, but not males, we found a significant interaction between selection and wheel access treatments: within the "active" group the difference in food consumption between selected and control animals was greater than in the "sedentary" group. At the end of the study, mice from the "active" and "sedentary" groups did not differ significantly in body mass; however, mice from the selected lines were approximately 6% smaller in body mass. Estimated lean body mass did not differ significantly either between selected and control lines or between wheel-access groups (P>0.3). Mice from selected lines had lower total body fat compared to mice from control lines (P=0.05; 24.5% reduction; LSMEANS) as did mice from the "active" compared to "sedentary" group (P= 0.03; 29.2% reduction; LSMEANS). Under these conditions, a sufficient explanation for the difference in body mass between the selected and control lines was the difference in fat content.     

Energy cost of wheel running in house mice: implications for coadaptation of locomotion and energy budgets

Laboratory house mice (Mus domesticus) that had experienced 10 generations of artificial selection for high levels of voluntary wheel running ran about 70% more total revolutions per day than did mice from random-bred control lines. The difference resulted primarily from increased average velocities rather than from increased time spent running. Within all eight lines (four selected, four control), females ran more than males. Average daily running distances ranged from 4.4 km in control males to 11.6 km in selected females. Whole-animal food consumption was statistically indistinguishable in the selected and control lines. However, mice from selected lines averaged approximately 10% smaller in body mass, and mass-adjusted food consumption was 4% higher in selected lines than in controls. The incremental cost of locomotion (grams food/revolution), computed as the partial regression slope of food consumption on revolutions run per day, did not differ between selected and control mice. On a 24-h basis, the total incremental cost of running (covering a distance) amounted to only 4.4% of food consumption in the control lines and 7.5% in the selected ones. However, the daily incremental cost of time active is higher (15.4% and 13.1% of total food consumption in selected and control lines, respectively). If wheel running in the selected lines continues to increase mainly by increases in velocity, then constraints related to energy acquisition are unlikely to be an important factor limiting further selective gain. More generally, our results suggest that, in small mammals, a substantial evolutionary increase in daily movement distances can be achieved by increasing running speed, without remarkable increases in total energy expenditure.     

Effects of voluntary exercise and genetic selection for high activity levels on HSP72 expression in house mice.

We studied expression of heat shock protein 72 (HSP72) in female mice from four replicate lines that had been selectively bred for high voluntary wheel running (S) and from four random-bred control lines (C). Mice from generation 23 were sampled after 6 days of wheel access, and those from generation 14 were sampled after 8 wk of access to wheels either free to rotate or locked. Mice from S lines ran approximately 2.6 times as many revolutions per day as did those from C lines. Western blotting of tissues from generation 23 mice indicated that S mice had elevated HSP72 expression in triceps surae muscle, but levels in spleen, kidney, heart, and lung were similar in S and C mice. HSP72 expression in triceps surae from generation 14 mice was measured by ELISA and analyzed with a two-way analysis of covariance. The interaction between wheel type and line type (S vs. C) was statistically significant, and subsequent analyses indicated that S mice had significantly elevated HSP72 expression only when housed with free wheels. Mice with the previously described mini-muscle phenotype (Houle-Leroy P, Guderley H, Swallow JG, and Garland T Jr. Am J Physiol Regul Integr Comp Physiol 284: R433-R443, 2003) occurred in both generations and had elevated HSP72 expression in triceps surae. For the generation 23 sample, wheel running as a covariate had a significant negative association with HSP72 expression, and the effect of line type was still statistically significant. Therefore, the increased HSP72 expression of S mice is not a simple proximate effect of their increased wheel running.     

Different effects of intensity and duration of locomotor activity on circadian period

An outstanding unresolved issue in chronobiology is how the level of locomotor activity influences length of the free-running, endogenous circadian period (tau). To address this issue, the authors studied a novel model, 4 replicate lines of laboratory house mice (Mus domesticus) that had been selectively bred for high wheel-running activity (S) and their 4 unselected control (C) lines. Previous work indicates that S mice run approximately twice as many revolutions/day and exhibit an altered dopaminergic function as compared with C mice. The authors report that S mice have a tau shorter by about 0.5 h as compared with C mice. The difference in tau was significant both under constant light (control lines: tau = 25.5 h; selected: tau = 24.9 h) and under constant dark (control lines: 23.7 h; selected: 23.4 h). Moreover, the difference remained statistically significant even when the effects of running speed and time spent running were controlled in ANCOVA. Thus, something more fundamental than just intensity or duration of wheel-running activity per se must underlie the difference in tau between the S and C lines. However, despite significant difference in total wheel-running activity between females and males, tau did not differ between the sexes. Similarly, among individuals within lines, tau was not correlated with wheel-running activity measured as total revolutions per day. Instead, tau tended to decrease with average running speed but increase with time spent running. Finally, within individuals, an increase in time spent running resulted in decreased tau in the next few days, but changes in running speed had no statistically significant effect. The distinctions between effects of duration versus intensity of an activity, as well as between the among- versus within-individual correlations, are critical to understanding the relation between locomotor activity and pace of the circadian clock.     

Body temperatures of house mice artificially selected for high voluntary wheel-running behavior: repeatability and effect of genetic selection

We studied rectal body temperatures of house mice (Mus domesticus) that had been artificially selected for high voluntary wheel running.1. At generation 17, mice from the four replicate selected lines ran, on average, 2.5-times as many revolutions/day as did mice from the four random-bred control lines.2. During the day, repeatability of individual differences in body temperature measured 4 days apart was low; at night, repeatability was statistically significant across three time scales (1 day, 1 week, 2 weeks).3. During the day, body temperatures of selected and control animals did not differ; at night, mice from selected lines had higher body temperatures. However, when amount of wheel running immediately prior to measurement was included as a covariate, the difference was no longer statistically significant.Higher body temperatures, associated with increased activity, might enhance locomotor abilities through Q10 effects, increase metabolic rate and food requirements, affect sleep patterns, and alter expression of heat-shock proteins.     

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.     

How to run far: multiple solutions and sex-specific responses to selective breeding for high voluntary activity levels

The response to uniform selection may occur in alternate ways that result in similar performance. We tested for multiple adaptive solutions during artificial selection for high voluntary wheel running in laboratory mice. At generation 43, the four replicate high runner (HR) lines averaged 2.85-fold more revolutions per day as compared with four non-selected control (C) lines, and females ran 1.11-fold more than males, with no sex-by-linetype interaction. Analysis of variance indicated significant differences among C lines but not among HR for revolutions per day. By contrast, average speed varied significantly among HR lines, but not among C, and showed a sex-by-linetype interaction, with the HR/C ratio being 2.02 for males and 2.45 for females. Time spent running varied among both HR and C lines, and showed a sex-by-linetype interaction, with the HR/C ratio being 1.52 for males but only 1.17 for females. Thus, females (speed) and males (speed, but also time) evolved differently, as did the replicate selected lines. Speed and time showed a trade-off among HR but not among C lines. These results demonstrate that uniform selection on a complex trait can cause consistent responses in the trait under direct selection while promoting divergence in the lower-level components of that trait.     

Response of Sod-2 enzyme activity to selection for high voluntary wheel running

The objective of this study was to examine the correlated response of anti-oxidant enzyme activity to selective breeding for increased voluntary wheel running in house mice. Activity of liver superoxide dismutase-2 (Sod-2), a free radical scavenger, was measured in four groups of mice. 'Active' individuals were housed in cages with attached wheels for 8 weeks beginning at weaning; 'sedentary' individuals were housed in cages with attached wheels that were prevented from rotating. Both of these treatments were applied to male and female mice from generation 14 of a replicated artificial selection experiment, which is composed of four lines selected for high wheel running and four randomly bred lines that serve as controls. In females, Sod-2 activity was significantly lower in selected vs control animals, regardless of presence/absence of a free-turning wheel. This difference suggests a trade-off between early-age voluntary wheel-running activity and Sod-2 activity. In males, Sod-2 activity was significantly affected by an interaction between selection group and activity group, with males from selected lines having lower Sod-2 activity relative to control males only in the sedentary treatment. These negative correlated responses of Sod-2 activity to selection on wheel running are discussed in the context of antagonistic pleiotropy models of aging and with respect to potential effects on lifespan.     

Effects of genetic selection and voluntary activity on the medial gastrocnemius muscle in house mice.

In a previous study, we found that in house mice both genetic selection (10 generations of artificial selection for high voluntary activity on running wheels) and access to running wheels (7-8 weeks) elicited a modest increase in maximal oxygen consumption. Based on these results, we hypothesized that genetic selection would affect the changes in endurance and oxidative capacity of the medial gastrocnemius (MG) muscle induced by wheel access (training response). Wheel access increased the isotonic endurance of the MG in both genetically selected and random-bred (control) mice. However, this exercise-induced improvement in isotonic endurance of the MG was similar between genetically selected and control mice. Wheel access also increased the succinate dehydrogenase activity of MG muscle fibers in both selected and control lines. However, this exercise-induced increase in succinate dehydrogenase activity was comparable between genetically selected and control animals. Taken together, these results indicate that the modest increase in maximal oxygen consumption associated with genetic selection is not reflected by the training-induced changes in oxidative capacity and endurance of MG muscle fibers.     

The effects of running activity on the reproductive axes of rodents

Access to a running wheel causes gonadal recrudescence in Syrian hamsters whose reproductive axes have been suppressed by housing them under short day lengths (Borer et al. 1983). The first experiment tested the generality of this phenomenon in a population of rodents that is genetically heterogeneous for reproductive photoresponsiveness. Male meadow voles (Microtus pennsylvanicus) of the two extreme phenotypes — reproductively photoresponsive and non-responsive — were either provided with a running wheel or housed without one. After 4 weeks with a wheel, the responsive voles had recovered full reproductive function, while the reproductive axes of responsive voles housed without wheels remained suppressed. Three experiments queried whether the use of a wheel would have reproductively stimulative effects in other rodents. First, intact male mice given access to wheels showed no increase in testis size when compared to mice housed without wheels. Likewise, locomotor activity had no effect on male rats whose testes were partially regressed in response to testosterone implants or on female mice whose estrous cycles were pheromonally suppressed by housing them in groups. Thus the neuroendocrine pathway used by locomotor activity to enhance the secretion of gonadotropin is specifically allied with the pathway used by photoperiod to control GnRH secretion.Abbreviations GnRH gonadotropin-releasing hormone - LH luteinizing hormone     

Effects of size, sex, and voluntary running speeds on costs of locomotion in lines of laboratory mice selectively bred for high wheel-running activity

Selective breeding for over 35 generations has led to four replicate (S) lines of laboratory house mice (Mus domesticus) that run voluntarily on wheels about 170% more than four random-bred control (C) lines. We tested whether S lines have evolved higher running performance by increasing running economy (i.e., decreasing energy spent per unit of distance) as a correlated response to selection, using a recently developed method that allows for nearly continuous measurements of oxygen consumption (VO2) and running speed in freely behaving animals. We estimated slope (incremental cost of transport [COT]) and intercept for regressions of power (the dependent variable, VO2/min) on speed for 49 males and 47 females, as well as their maximum VO2 and speeds during wheel running, under conditions mimicking those that these lines face during the selection protocol. For comparison, we also measured COT and maximum aerobic capacity (VO2max) during forced exercise on a motorized treadmill. As in previous studies, the increased wheel running of S lines was mainly attributable to increased average speed, with males also showing a tendency for increased time spent running. On a whole-animal basis, combined analysis of males and females indicated that COT during voluntary wheel running was significantly lower in the S lines (one-tailed P=0.015). However, mice from S lines are significantly smaller and attain higher maximum speeds on the wheels; with either body mass or maximum speed (or both) entered as a covariate, the statistical significance of the difference in COT is lost (one-tailed P> or =0.2). Thus, both body size and behavior are key components of the reduction in COT. Several statistically significant sex differences were observed, including lower COT and higher resting metabolic rate in females. In addition, maximum voluntary running speeds were negatively correlated with COT in females but not in males. Moreover, males (but not females) from the S lines exhibited significantly higher treadmill VO2max as compared to those from C lines. The sex-specific responses to selection may in part be consequences of sex differences in body mass and running style. Our results highlight how differences in size and running speed can account for lower COT in S lines and suggest that lower COT may have coadapted in response to selection for higher running distances in these lines.     

Epigenetic Effects on Integration of Limb Lengths in a Mouse Model: Selective Breeding for High Voluntary Locomotor Activity

Mammals exhibit a similar pattern of integration among homologous limb elements, the strength of which is believed to vary in response to selection for functional coordination or similarity. Although integration is hypothesized to primarily reflect the effect of genes intrinsic to limbs, extrinsic genetic or epigenetic factors may also affect the strength of integration through their impact on the magnitude and direction of skeletal variance or covariance. Such factors as neuromuscular coordination or bone-muscle interactions may therefore play a role in both canalization and the structure or magnitude of limb integration. If this were the case, then increased levels of locomotor activity would be predicted to increase canalization and the magnitude of covariation between limbs. To investigate whether postnatal activity levels can have a significant effect on variance within or covariance among homologous limb elements, we compared four groups of male mice from a long-term selective breeding experiment: (1) mice from lines bred for increased voluntary activity on running wheels and allowed free access to a wheel for 8 weeks beginning at weaning (“active”), (2) selected mice that did not have wheel access (“sedentary”), (3) active mice from non-selected control lines, and (4) sedentary control mice. Mice from selected lines that had wheel access ran significantly more than control-line mice. However, when controlled for activity, linetype, and body mass, results indicate few significant differences in means, variance, or covariation structure, and no significant differences in integration between limbs, suggesting that postnatal activity levels do not significantly affect canalization or integration of limb lengths. A possible explanation for this result is that whereas baseline levels of postnatal activity may help to maintain patterns of variance and integration, increased levels of activity do not further increase these measures. Investigations into disrupted epigenetic processes (e.g., via models in which neuromuscular coordination is impaired) are required to further test hypotheses about how canalization or integration of limb variation is affected by epigenetic factors.     

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.     

Voluntary Exercise and Its Effects on Body Composition Depend on Genetic Selection History

Little is known about how genetic variation affects the capacity for exercise to change body composition. We examined the extent to which voluntary exercise alters body composition in several lines of selectively bred mice compared to controls. Lines studied included high runner (HR) (selected for high wheel running), M16 (selected for rapid weight gain), Institute of Cancer Research (ICR) (randomly bred as control for M16), M16i (an inbred line derived from M16), HE (selected for high percentage of body fat while holding body weight constant), LF (selected for low percentage of body fat), C57BL/6J (common inbred line), and the F1 between HR and C57BL/6J. Body weight and body fat were recorded before and after 6 days of free access to running wheels in males and females that were individually caged. Total food intake was measured during this 6‐day period. All pre‐ and postexercise measures showed significant strain effects. While HR mice predictably exercised at higher levels, all other selection lines had decreased levels of wheel running relative to ICR. The HR × B6 F1 ran at similar levels to HR demonstrating complete dominance for voluntary exercise. Also, all strains lost body fat after exercise, but the relationships between exercise and changes in percent body were not uniform across genotypes. These results indicate that there is significant genetic variation for voluntary exercise and its effects on body composition. It is important to carefully consider genetic background and/or selection history when using mice to model effects of exercise on body composition, and perhaps, other complex traits as well.     

Testosterone and photoperiod interact to regulate locomotor activity in male hamsters

Testicular size, plasma testosterone levels, copulatory behavior, and daily locomotor activity are reduced in male hamsters after 10 weeks of exposure to short days. The role of testosterone in the short day-induced decline in locomotor activity was investigated, determining whether or not photoperiod could alter the effect of testosterone on activity. Castrated adult hamsters were allowed to acclimate to running wheels (wired to digital counters) and then were kept on either long (L:D 14:10) or short (L:D 6:18) days for 60 days. On Day 60, half of the animals on each light cycle were implanted with 12-mm-long testosterone-filled Silastic capsules; half received empty capsules. Digital counting of wheel-running activity continued for another 140 days. Blood samples taken on Day 200 confirmed L:D 14:10 and L:D 6:18 testosterone-treated hamsters had equivalent plasma testosterone levels. After an initial decline in activity, L:D 14:10 animals exhibited a progressive rise in mean running activity (from ~2000 to ~5000 wheel revolutions per day) through 100 days after the initiation of testosterone treatment. In contrast, activity levels in testosterone-treated L:D 6:18 animals remained uniform (~2000 wheel revolutions per day) during this time, indicating exposure to short days rendered the hamsters less sensitive to the stimulatory effect of testosterone on activity. Of further interest was a marked increase in activity after 160–200 short days in animals treated with either testosterone-filled or empty capsules. It appears the total amount of daily locomotor activity in the hamster is modulated by circulating testosterone levels in a manner which is dependent upon the environmental photoperiod.     

Wheel running in the wild

The importance of exercise for health and neurogenesis is becoming increasingly clear. Wheel running is often used in the laboratory for triggering enhanced activity levels, despite the common objection that this behaviour is an artefact of captivity and merely signifies neurosis or stereotypy. If wheel running is indeed caused by captive housing, wild mice are not expected to use a running wheel in nature. This however, to our knowledge, has never been tested. Here, we show that when running wheels are placed in nature, they are frequently used by wild mice, also when no extrinsic reward is provided. Bout lengths of running wheel behaviour in the wild match those for captive mice. This finding falsifies one criterion for stereotypic behaviour, and suggests that running wheel activity is an elective behaviour. In a time when lifestyle in general and lack of exercise in particular are a major cause of disease in the modern world, research into physical activity is of utmost importance. Our findings may help alleviate the main concern regarding the use of running wheels in research on exercise.     

The thalamic intergeniculate leaflet mediates locomotor activity-induced reversal of phenotype in photoperiod nonresponsive Siberian hamsters

The role of the intergeniculate leaflet of the thalamus (IGL) in photoperiod responsiveness was examined in a laboratory-selected line of photoperiod nonresponsive (NR) Siberian hamsters. NR hamsters fail to exhibit typical winter-type responses (i.e., gonadal regression and development of winter-type pelage) when exposed to short day lengths (e.g., 10 h of light/day). Earlier studies revealed that NR hamsters will exhibit winter-type responses when exposed to short photoperiod if they are given free access to a running wheel. The present study tested the hypothesis that this locomotor activity-induced reversal of phenotype is dependent on the IGL. Male NR hamsters underwent destruction of the IGL prior to being housed in short day lengths in cages equipped with running wheels. Activity rhythms were monitored for 8 weeks, after which time pelage response and paired testes weights were obtained. In contrast to sham-operated NR animals given access to running wheels, IGL-ablated animals showed no increase in the duration of nocturnal running wheel activity and became active later in the night than sham-lesioned animals. Lesioned animals also failed to exhibit the typical short photoperiod-induced gonadal regression and pelage molt. The results implicate the IGL in the mechanism by which running wheel activity can influence photoperiodic responses.