-Natural variation in neuroendocrine traits is poorly understood, despite the importance of variation in brain function and evolution. Most rodents in the temperate zones inhibit reproduction and other nonessential functions in short winter photoperiods, but some have little or no reproductive response. We tested whether genetic variability in reproductive seasonality is related to individual differences in the neuronal function of the gonadotropin-releasing hormone network, as assessed by the number and location of mature gonadotropin-releasing hormonesecreting neurons under inhibitory and excitatory photoperiods. The experiments used lines of Peromyscus leucopus previously developed by selection from a wild population. One line contained individuals reproductively inhibited by short photoperiod, and the other line contained individuals nonresponsive to short photoperiod. Expression of mature gonadotropin-releasing hormone (GnRH) immunoreactivity in the brain was detected using SMI-41 antibody in the single-labeled avidin-biotin-peroxidase-complex method. Nonresponsive mice had 50% more immunoreactive GnRH neurons than reproductively inhibited mice in both short-and long-day photoperiods. The greatest differences were in the anterior hypothalamus and preoptic areas. In contrast, we detected no significant within-lines differences in the number or location of immunoreactive GnRH neurons between photoperiod treatments. Our data indicate that high levels of genetic variation in a single wild population for a specific neuronal trait are related to phenotypic variation in a life history trait, i.e., winter reproduction. Variation in GnRH neuronal activity may underlie some of the natural reproductive and life history variation observed in wild populations of P. leucopus. Similar genetic variation in neuronal traits may be present in humans and other species. genetic variation; artificial selection; seasonality; evolutionary physiology; brain variation; gonadotropin-releasing hormone WITHIN-POPULATION GENETIC VARIATION regulating the abundance, location, and connections of neurons must contribute to evolution of brain function. Similarly, natural genetic variation in neuronal traits is presumably responsible for some proportion of intraspecific functional variation in vertebrates. Because neural circuitry regulates reproductive physiology and behavior, neural variation is likely to explain some unknown proportion of life history variation within as well as among species. At present, almost nothing is known about natural levels of genetically based neuroendocrine physiological variation related to life history variation within species of mammals. The physiological link between genes and life history patterns is important because genes must act on life history traits through physiological mechanisms, and thus physiological variation may shape or constrain life history evolution (16). Understanding natural neuroendocrine variation related to life history traits might help us learn how rapidly brains adapt to current cha...

The evolution of mammalian brain function depends in part on levels of natural, heritable variation in numbers, location, and function of neurons. However, the nature and amount of natural genetic variation in neural traits and their physiological link to variation in function or evolutionary change are unknown. We estimated the level of within-population heritable variation in the number of gonadotropin-releasing hormone (GnRH) neurons, which play a major role in reproductive regulation, in an unselected outbred population recently derived (<10 generations) from a single natural population of white-footed mice (Peromyscus leucopus, Rafinesque). Young adult male mice exhibited an approximately threefold variation in the number of neurons immunoreactive for GnRH in the brain areas surveyed, as detected using SMI-41 antibody with a single-label avidin-biotin complex method. Consistent with earlier findings of selectable variation in GnRH neurons in this population, the level of genetic variation in this neuronal trait within this single population was high, with broadsense heritability using full-sib analysis estimated at 0.72 (P<0.05). Either weak selection on this trait or environmental variation that results in inconsistent selection on this trait might allow a high level of variation in this population.

BackgroundResponsiveness to changing photoperiods from summer to winter seasons is an important but variable physiological trait in most temperate-zone mammals. Variation may be due to disorders of melatonin secretion or excretion, or to differences in physiological responses to similar patterns of melatonin secretion and excretion. One potential cause of nonphotoresponsiveness is a failure to secrete or metabolize melatonin in a pattern that reflects photoperiod length.MethodsThis study was performed to test whether a strongly photoresponsive rat strain (F344) and strongly nonphotoresponsive rat strain (HSD) have similar circadian urinary excretion profiles of the major metabolite of melatonin, 6-sulfatoxymelatonin (aMT6s), in long-day (L:D 16:8) and short-day (L:D 8:16) photoperiods. The question of whether young male HSD rats would have reproductive responses to constant dark or to supplemental melatonin injections was also tested. Urinary 24-hour aMT6s profiles were measured under L:D 8:16 and L:D 16:8 in young male laboratory rats of a strain known to be reproductively responsive to the short-day photoperiod (F344) and another known to be nonresponsive (HSD).ResultsBoth strains exhibited nocturnal rises and diurnal falls in aMT6s excretion during both photoperiods, and the duration of the both strains' nocturnal rise was longer in short photoperiod treatments. In other experiments, young HSD rats failed to suppress reproduction or reduce body weight in response to either constant dark or twice-daily supplemental melatonin injections.ConclusionThe results suggest that HSD rats may be nonphotoresponsive because their reproductive system and regulatory system for body mass are unresponsive to melatonin.

Genetic variation contributes to individual differences in obesity, but defining the exact relationships between naturally occurring genotypes and their effects on fatness remains elusive. As a step toward positional cloning of previously identified body composition quantitative trait loci (QTLs) from F2 crosses of mice from the C57BL/6ByJ and 129P3/J inbred strains, we sought to recapture them on a homogenous genetic background of consomic (chromosome substitution) strains. Male and female mice from reciprocal consomic strains originating from the C57BL/6ByJ and 129P3/J strains were bred and measured for body weight, length, and adiposity. Chromosomes 2, 7, and 9 were selected for substitution because previous F2 intercross studies revealed body composition QTLs on these chromosomes. We considered a QTL confirmed if one or both sexes of one or both reciprocal consomic strains differed significantly from the host strain in the expected direction after correction for multiple testing. Using these criteria, we confirmed two of two QTLs for body weight (Bwq5-6), three of three QTLs for body length (Bdln3-5), and three of three QTLs for adiposity (Adip20, Adip26 and Adip27). Overall, this study shows that despite the biological complexity of body size and composition, most QTLs for these traits are preserved when transferred to consomic strains; in addition, studying reciprocal consomic strains of both sexes is useful in assessing the robustness of a particular QTL.