SUMMARY Epigenetic information can be inherited through the mammalian germline, and represents a plausible transgenerational carrier of environmental information. To test whether transgenerational inheritance of environmental information occurs in mammals, we carried out an expression profiling screen for genes in mice that responded to paternal diet. Offspring of males fed a low protein diet exhibited elevated hepatic expression of many genes involved in lipid and cholesterol biosynthesis, and decreased levels of cholesterol esters, relative to the offspring of males fed a control diet. Epigenomic profiling of offspring livers revealed numerous modest (~20%) changes in cytosine methylation depending on paternal diet, including reproducible changes in methylation over a likely enhancer for the key lipid regulator PPARα. These results, in conjunction with recent human epidemiological data, indicate that parental diet can affect cholesterol and lipid metabolism in offspring, and define a model system to study environmental reprogramming of the heritable epigenome.

All animals evaluate the salience of external stimuli and integrate them with internal physiological information into adaptive behavior. Natural and sexual selection impinge on these processes, yet our understanding of behavioral decision-making mechanisms and their evolution is still very limited. Insights from mammals indicate that two neural circuits are of crucial importance in this context: the social behavior network and the mesolimbic reward system. Here we review evidence from neurochemical, tract-tracing, developmental, and functional lesion/stimulation studies that delineates homology relationships for most of the nodes of these two circuits across the five major vertebrate lineages: mammals, birds, reptiles, amphibians, and teleost fish. We provide for the first time a comprehensive comparative analysis of the two neural circuits and conclude that they were already present in early vertebrates. We also propose that these circuits form a larger social decision-making (SDM) network that regulates adaptive behavior. Our synthesis thus provides an important foundation for understanding the evolution of the neural mechanisms underlying reward processing and behavioral regulation. J. Comp. Neurol. 519:3599-3639, 2011. INDEXING TERMS: social behavior; comparative neuroanatomy; amphibian; reptile; bird; teleost; reward system; social behavior network; limbic system; neural circuitsThroughout their lives, all animals constantly face situations that provide either challenges (e.g., aggression, predation) or opportunities (e.g., reproduction, foraging, habitat selection) (for a detailed review, see O'Connell and Hofmann, 2011). In all cases, environmental cues are processed by sensory systems into a meaningful biological signal while internal physiological cues (e.g., condition, maturity) and prior experience are integrated at the same time. This process usually results in behavioral actions that are adaptive, i.e., beneficial to the animal. To accomplish this, an animal's nervous system must evaluate the salience of a stimulus and elicit a context-appropriate behavioral response. Despite tremendous progress in understanding the ecology and evolution of social behavior (Lorenz, 1952;Tinbergen, 1963;Lehrman, 1965;von Frisch, 1967;Krebs and Davies, 1993;Stephens, 2008), it is less understood where in the brain these decisions (e.g., about mate choice or territory defense) are made and how these brain circuits have arisen over the course of vertebrate evolution.Recent research has begun to decipher the neural basis of social decision-making. In mammals in particular, the neural circuits that evaluate stimulus salience and/or regulate social behavior have been uncovered to some degree: the mesolimbic reward system and social behavior network (Fig. 1). It is becoming increasingly clear that the reward system (including but not limited to the midbrain dopaminergic system) is the neural circuit where the salience of an external stimulus is evaluated (Deco and Rolls, 2005;Wickens et al., 2007), as appetitive beh...

Animals evaluate and respond to their social environment with adaptive decisions. Revealing the neural mechanisms of such decisions is a major goal in biology. We analyzed expression profiles for 10 neurochemical genes across 12 brain regions important for decision-making in 88 species representing five vertebrate lineages. We found that behaviorally relevant brain regions are remarkably conserved over 450 million years of evolution. We also find evidence that different brain regions have experienced different selection pressures, because spatial distribution of neuroendocrine ligands are more flexible than their receptors across vertebrates. Our analysis suggests that the diversity of social behavior in vertebrates can be explained, in part, by variations on a theme of conserved neural and gene expression networks.

Complex brains and behaviors have occurred repeatedly within vertebrate classes throughout evolution. What adaptive pressures drive such changes? Both environmental and social features have been implicated in the expansion of select brain structures, particularly the telencephalon. East African cichlid fishes provide a superb opportunity to analyze the social and ecological correlates of neural phenotypes and their evolution. As a result of rapid, recent, and repeated radiations, there are hundreds of closely-related species available for study, with an astonishing diversity in habitat preferences and social behaviors. In this study, we present quantitative ecological, social, and neuroanatomical data for closely-related species from the (monophyletic) Ectodini clade of Lake Tanganyikan cichlid fish. The species differed either in habitat preference or social organization. After accounting for phylogeny with independent contrasts, we find that environmental and social factors differentially affect the brain, with environmental factors showing a broader effect on a range of brain structures compared to social factors. Five out of seven of the brain measures show a relationship with habitat measures. Brain size and cerebellar size are positively correlated with species number (which is correlated with habitat complexity); the medulla and olfactory bulb are negatively correlated with habitat measures. The telencephalon shows a trend toward a positive correlation with rock size. In contrast, only two brain structures, the telencephalon and hypothalamus, are correlated with social factors. Telencephalic size is larger in monogamous species compared to polygamous species, as well as with increased numbers of individuals; monogamy is also associated with smaller hypothalamic size. Our results suggest that selection or drift can act independently on different brain regions as the species diverge into different habitats and social systems.

Since recent observations indicate that treatment with high-dose intravenous polyvalent intact immunoglobulin leads to a rapid reversal of thrombocytopenia in the idiopathic thrombocytopenic purpura (ITP) of childhood, we decided to apply this treatment to adults with ITP and to test the possibility that the effect of the immunoglobulin might be attributable to transient blockade of the reticuloendothelial system. Using sequential clearance studies of autologous 99mTc-labeled and anti-Rh(D)-sensitized erythrocytes in four adults with ITP who were treated with total doses of 1 to 1.5 g of immunoglobulin per kilogram of body weight, we found that a transient rise in platelet counts to normal levels within four to five days was accompanied by a marked temporary prolongation of the immune-particle clearance time. These data suggest that commercial intravenous immunoglobulin preparations may interfere with phagocyte Fc-receptor-mediated immune clearance. Since platelets in ITP treated with immunoglobulin were fully hemostatic, this type of therapy may allow surgical procedures to be performed safely in patients with this disease.