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Biomedical subjects

N D Henderson

Publications and source records attributed to N D Henderson.

At least 19 recordsLinked to original sources

Individual differences in sensitivity to nicotine in mice: response to six generations of selective breeding.

Four hundred seventeen heterogeneous stock mice were tested for their relative sensitivity to a low dose of nicotine (0.75 mg/kg) using activity in an automated Y-maze and body temperature as response measures. A wide spectrum of individual responsiveness to nicotine, ranging from complete suppression of activity to stimulation above baseline activity, was found. Replicate measures taken 1 week later on the same animals showed the responses to nicotine to be reliable and reproducible. Activity levels and body temperatures following nicotine administration were highly correlated (r = 0.60, df = 415). From analysis of between-litter proportions of variance, the heritability of nicotine-influenced activity was estimated to be 0.12, indicating that selective breeding for differential responsiveness to nicotine would be possible. The 10 most activated and 10 most depressed male and female mice were chosen as breeders for replicate nicotine activated (NA) and nicotine depressed (ND) lines, respectively. The selection criterion was nicotine-induced activity corrected for baseline activity using regression residuals. After six generations of selective breeding a good response to selection was obtained, although the response was better for the ND than for the NA lines. Realized heritability for responsiveness to nicotine calculated from the six selected generations was found to be 0.20, or slightly greater than that estimated from the foundation population. There were no significant differences in response to selection between the replicate NA or ND lines. Nicotine-induced body temperature was measured as a correlated response to selection, and was found to remain highly correlated with nicotine-induced locomotor activity. The response was more robust for the ND lines than it was for the NA lines. In contrast to the large differences between the ND and NA lines in locomotor activity and body temperatures following nicotine administration, mean baseline activities and body temperatures remained nearly identical throughout. This indicates that selection acted specifically on nicotine-induced responses, and not on baseline measurements, as predicted for response to a selection criterion based on regression residuals.

Animals

Genetic analysis of an avoidance-avoidance response in Mus domesticus.

Latency to leave a lighted platform and enter a novel chamber in which other mice had received shock was measured in 2592 mice from eight inbred strains and all 56 F1 crosses. An analysis of the diallel matrix indicated a clear genetic architecture, although genetic effects accounted for only 10% of the total phenotypic variance. Dominance favoring a slight delay in chamber entry suggested a selective advantage in spending a longer time on some elements in the behavioral chain involved in avoidance-avoidance responses. Inbred strains showed greater litter variance than F1 hybrids, suggesting greater developmental buffering of heterozygotes. Both the genetic architecture and the strain rankings differ from those typically found in open field and similar tests of locomotor activity. The results illustrate the problem of interpreting behavior genetic results in terms of proportions of total phenotypic variance and difficulties in generalizing to ancestral or other populations in an attempt to interpret genetic results in an evolutionary context when reliability is low.

Animals

Interpreting studies that compare high- and low-selected lines on new characters.

The attempt to characterize high- and low-selected lines on new variables poses serious interpretative problems when replicate lines are not available. Modest but significant line differences on new measures may be due to genetic drift totally irrelevant to the originally selected trait. Often these differences are exaggerated by inappropriate analysis using individual subject measurements rather than family means. Mean differences in high- and low-selected lines on new characters should not be ascribed to the originally selected trait unless (1) genetic drift can be estimated through the use of replicate lines, (2) the standardized mean difference exceeds 1/4 of the equivalent difference on the original selected trait, or (3) strong predictions involving multiple noncontingent measures are unconditionally supported. For most purposes of analysis, line means can be considered individual data points which can be used to compute correlations among measures. An alternative to selection with replicates--two-stage testing of commercially available inbred strains--should be considered when large genetic correlations between the characters are expected.

Animals

Genetic influences on behavior of infant Mus domesticus: a comparison of results from diallels derived from single and multiple populations.

A complete diallel cross was generated from six Jax inbred strains of Mus domesticus from diverse origins and a second 6 x 6 diallel generated from strains derived from a single wild population. During their second day of life, infants from both diallels were tested for latency to orient toward and root beneath mothers and, in a separate test, for latency to attach to mother's nipple. Rooting latency showed a significant additive maternal strain effect but little systematic effect of pup genotype. Nipple attachment latencies exhibited complete genetic dominance favoring rapid attachment, with no maternal effects. Patterns of genetic and influences obtained from the two diallels were highly similar for both behaviors, suggesting that for many traits the requirement that strains be drawn from a common base population may be relaxed.

Animals

A fit mouse is a hoppy mouse: jumping behavior in 15-day-old Mus musculus.

An analysis of a juvenile hopping response from an 8 X 8 diallel cross is used to demonstrate the experimental genetic approach for testing presumed adaptive fitness of behaviors in developing organisms. In accordance with predictions, the explosive jumping behavior exhibited by 15-day mice is characterized by a pattern of genetic dominance toward high expression of the trait. Wild mice show even more vigorous responses, indicating that selection pressures maintaining high responding have been relaxed during domestication. These data suggest some applications and limitations of genetic methods for the study of behavioral evolution as related to development.

Adaptation, Biological

Genetic influences on locomotor activity in 11-day-old housemice.

An 8 X 8 diallel analysis of locomotor activity related to nest return in mice just prior to eye opening indicated a pattern of dominance toward high activity, with little additive genetic variance. Groups of laboratory-reared wild mice did not differ from each other or from the diallel mean, suggesting little relaxation of selection toward rapid nest return during domestication. In contrast to the nest return situation, an eight-strain triple test-cross analysis of locomotion in a test environment unlikely to be encountered by 11-day-old mice indicated only additive genetic variance, with no evidence of dominance for increased activity. When measured in an ecologically relevant environment, the nature of genetic variation appears to change with age in a manner concordant with what one would intuitively assume to be adaptive behavior at each stage of development.

Aging

Genetic dominance for low activity in infant mice.

Locomotor activity of 2,140 four-day-old inbred, hybrid, and wild mice was measured. Consonant with the prediction that high rates of locomotor activity would be maladaptive in infant mice, hybrids were less active than inbred lines. A triple test cross analysis indicated low heritability and nearly complete dominance toward low activity. Mice from wild stock were even less active than hybrids, which suggests that selection pressures for low infantile activity have relaxed during laboratory domestication. A test is described for estimating changes in selection pressures resulting from laboratory rearing.

Animals

The role of motor learning and cage size in the early enrichment effect in mice.

Three experiments with C57BL/10J mice examined the possible roles of cage size and simple motor practice as factors responsible for producing improved performance of animals reared in enriched environments. Neither factor was found sufficient to improve subsequent performance in a food-seeking task. Mice reared in flat environments containing a variety of objects, but designed to prevent any climbing practice, out-performed nonenriched animals on a task requiring extensive climbing activity.

Animals

Short exposures to enriched environments can increase genetic variability of behavior in mice.

Previous work indicates that mice of different genotypes reared in enriched environments show differential increases in performance on a food-seeking task. In this study 2 experiments examined the effects in selected mice strains of short exposures to such enrichment. Experiment 1 indicated that 48 hr of exposure to enriched cages was sufficient to produce results found previously when subjects were reared from birth in enriched cages. Experiment 2 indicated that as little as 6 hr of exposure to an enriched cage was sufficient to produce almost maximal enrichment effects in C57BL/10J mice.

Age Factors