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Behavioral evolution relies on genetic changes, yet few social behaviors can be traced to specific genetic sequences in vertebrates. Here, we show experimental evidence that differentiation of a single gene has contributed to divergent behavioral phenotypes in the white-throated sparrow, a common North American songbird. In this species, one of two alleles ofESR1, encoding estrogen receptor α (ERα), has been captured inside a differentiating supergene that segregates with an aggressive phenotype, such thatESR1expression predicts aggression. Here, we show that the aggressive phenotype associated with the supergene is prevented byESR1knockdown in a single brain region. Next, we show that in a free-living population, aggression is predicted by allelic imbalance favoring the supergene allele.Cis-regulatory variation between the two alleles affects transcription factor binding sites, DNA methylation, and rates of transcription. This work provides a rare illustration of how genotypic divergence has led to behavioral phenotypic divergence in a vertebrate.

Perivascular stromal cells, including mesenchymal stem/stromal cells (MSCs), secrete paracrine factor in response to exercise training that can facilitate improvements in muscle remodeling. This study was designed to test the capacity for muscle-resident MSCs (mMSCs) isolated from young mice to release regenerative proteins in response to mechanical strain in vitro, and subsequently determine the extent to which strain-stimulated mMSCs can enhance skeletal muscle and cognitive performance in a mouse model of uncomplicated aging. Protein arrays confirmed a robust increase in protein release at 24h following an acute bout of mechanical strain in vitro (10%, 1Hz, 5h) compared to non-strain controls. Aged (24month old), C57BL/6 mice were provided bilateral intramuscular injection of saline, non-strain control mMSCs, or mMSCs subjected to a single bout of mechanical strain in vitro (4×104). No significant changes were observed in muscle weight, myofiber size, maximal force, or satellite cell quantity at 1 or 4wks between groups. Peripheral perfusion was significantly increased in muscle at 4wks post-mMSC injection (p

The white-throated sparrow (Zonotrichia albicollis) represents a powerful model in behavioral neuroendocrinology because it occurs in two plumage morphs that differ with respect to steroid-dependent social behaviors. Birds of the white-striped (WS) morph engage in more territorial aggression than do birds of the tan-striped (TS) morph, and the TS birds engage in more parenting behavior. This behavioral polymorphism is caused by a chromosomal inversion that has captured many genes, including estrogen receptor alpha (ERα). In this study, we tested the hypothesis that morph differences in aggression might be explained by differential sensitivity to estradiol (E2). We administered E2 non-invasively to non-breeding white-throated sparrows and quantified aggression toward a conspecific 10 min later. E2 administration rapidly increased aggression in WS birds but not TS birds, consistent with our hypothesis that differential sensitivity to E2 may at least partially explain morph differences in aggression. To query the site of E2 action in the brain, we administered E2 and quantified Egr-1 expression in brain regions in which expression of ERα is known to differ between the morphs. E2 treatment decreased Egr-1 immunoreactivity in nucleus taeniae of the amygdala, but this effect did not depend on morph. Overall, our results support a role for differential effects of E2 on aggression in the two morphs, but more research will be needed to determine the neuroanatomical site of action.

Rationale Evidence suggests that 4 weeks of voluntary wheel running abolishes conditioned place preference (CPP) for cocaine in male C57BL/6J mice. Objectives To determine the duration and timing of exposure to running wheels necessary to reduce CPP, and the extent to which the running per se influences CPP as compared to environmental enrichment without running. Methods A total of 239 males were conditioned for 4 days twice daily with cocaine (10 mg/kg) and then split into 7 intervention groups prior to 4 days of CPP testing. Experiment 1 consisted of two groups housed as follows: short sedentary group (SS; n = 20) in normal cages for 1 week; the short running group (SR; n = 20) with running wheels for 1 week. Experiment 2 consisted of five groups housed as follows; short 1 week of running followed by a 3 week sedentary period (SRS; n = 20); a 3 week sedentary period followed by 1 week of running (SSR; n = 20); long sedentary group (LS; n = 66) in normal cages for 4 weeks; long running group (LR; n = 66) with running wheels for 4 weeks; and long environmental enrichment group (EE; n = 27) with toys for 4 weeks. Results Levels of running were similar in all running groups. Both running and environmental enrichment reduced CPP relative to sedentary groups. Conclusions Results suggest that the abolishment of cocaine CPP from running is robust and occurs with as low as 1 week of intervention but may be related to enrichment component of running rather than physical activity.