Behavioral neuroendocrinology in nontraditional species of mammals: Things the ‘knockout’ mouse CAN'T tell us

Abstract

The exploration of many of the fundamental features of mammalian behavioral neuroendocrinology has benefited greatly throughout the short history of the discipline from the study of highly inbred, genetically characterized rodents and several other "traditional" exemplars. More recently, the impact of genomic variation in the determination of complex neuroendocrine and behavioral systems has advanced through the use of single and multiple gene knockouts or knockins. In our essay, we argue that the study of nontraditional mammals is an essential approach that complements these methodologies by taking advantage of allelic variation produced by natural selection. Current and future research will continue to exploit these systems to great advantage and will bring new techniques developed in more traditional laboratory animals to bear on problems that can only be addressed with nontraditional species. We highlight our points by discussing advances in our understanding of neuroendocrine and behavioral systems in phenomena of widely differing time scales. These examples include neuroendocrine variation in the regulation of reproduction across seasons in Peromyscus, variation in parental care by biparental male rodents and primates within a single infant rearing attempt, and circadian variation in the regulation of the substrates underlying mating in diurnal vs. nocturnal rodents. Our essay reveals both important divergences in neuroendocrine systems in our nontraditional model species, and important commonalities in these systems.

Antidepressants Reverse Short-Photoperiod-Induced, Forced Swim Test Depression-Like Behavior in the Diurnal Fat Sand Rat: Further Support for the Utilization of Diurnal Rodents for Modeling Affective Disorders

“…The identification of the most appropriate model animal to explore specific questions had repeatedly been mentioned as a critical component in the development of good models for disease [20,35] . In that context, the use of nontraditional animals had already been demonstrated to be a resource for knowledge that cannot be obtained using standard laboratory species.…”

Translational Impact

“…We believe that studying the variation in the P. maniculatus species complex experimental system has a unique potential for understanding the relationship between environment-associated adaptations and mammalian disease susceptibility. In general, we suggest that further studies of mammals with natural allelic combinations will yield insights that are not possible with mixed and/or inbred lines (Smale et al, 2005). …”

“…Such models could be used to identify and study interactions among alleles conferring disease susceptibility in humans. Commonly used laboratory rodents and domesticated animals are not ideal for such studies because they do not represent naturally occurring populations (owing to both allelic combinations and homozygosity) (Beck et al, 2000;Smale et al, 2005).…”

Cortical evolution in mammals: The bane and beauty of phenotypic variability

“…Important for this review, the volume and pattern of GnRh secretion varies with external cues, such as photoperiod, food availability, stress, and conflict (51, 52), which in turn generates variable release of LH and FSH by the anterior pituitary and so on. Natural variation in genes that regulate this pathway has also been demonstrated in different individuals within populations of deer mice and white-footed mice (51,53). Thus, variability in the brain and behavior can be generated through external or internal cues.…”