December 8, 2010, Filed Under: 2010Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals Citation: Carone BR, Fauquier L, Habib N, Shea JM, Hart CE, Li R, Bock C, Li C, Gu H, Zamore PD, et al. Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals. Cell [Internet]. 143 (7) :1084 – 1096. Publisher’s Version Abstract 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 Ppara. 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. © 2010 Elsevier Inc. 2010.carone.cell_.pdf
November 23, 2010, Filed Under: 2011Characterization of the dopamine system in the brain of the tungara frog, Physalaemus pustulosus Citation: O’Connell LA, Matthews BJ, Ryan MJ, Hofmann HA. Characterization of the dopamine system in the brain of the tungara frog, Physalaemus pustulosus. Brain, Behavior and Evolution. 76 (3-4) :211 – 225. Abstract Dopamine is an evolutionarily ancient neurotransmitter that plays an essential role in mediating behavior. In vertebrates, dopamine is central to the mesolimbic reward system, a neural network concerned with the valuation of stimulus salience, and to the nigrostriatal motor system and hypothalamic nuclei involved in the regulation of locomotion and social behavior. In amphibians, dopaminergic neurons have been mapped out in several species, yet the distribution of dopaminoreceptive cells is unknown. The túngara frog, Physalaemus pustulosus, is an excellent model system for the study of neural mechanisms by which valuations of stimuli salience and social decisions are made, especially in the context of mate choice. In order to better understand where dopamine acts to regulate social decisions in this species, we have determined the distribution of putative dopaminergic cells (using tyrosine hydroxylase immunohistochemistry) and cells receptive to dopaminergic signaling (using DARPP-32 immunohistochemistry) throughout the brain of P. pustulosus. The distribution of dopaminergic cells was comparable to other anurans. DARPP-32 immunoreactivity was identified in key brain regions known to modulate social behavior in other vertebrates including the proposed anuran homologues of the mammalian amygdalar complex, nucleus accumbens, hippocampus, striatum, preoptic area, anterior hypothalamus, ventromedial hypothalamus, and ventral tegmental area/substantia nigra pars compacta. Due to its widespread distribution, DARPP-32 likely also plays many roles in non-limbic brain regions that mediate non-social information processing. These results significantly extend our understanding of the distribution of the dopaminergic system in the anuran brain and beyond. 2010.oconnell.bbe_.pdf
October 6, 2010, Filed Under: 2010Social and ecological regulation of a decision-making circuit. Citation: Neumeister H, Whitaker KW, Hofmann HA, Preuss T. Social and ecological regulation of a decision-making circuit. Journal of neurophysiology. 104 (October 2010) :3180 – 3188. Abstract Ecological context, sensory inputs, and the internal physiological state are all factors that need to be integrated for an animal to make appropriate behavioral decisions. However, these factors have rarely been studied in the same system. In the African cichlid fish Astatotilapia burtoni, males alternate between two phenotypes based on position in a social hierarchy. When dominant (DOM), fish display bright body coloration and a wealth of aggressive and reproductive behavioral patterns that make them conspicuous to predators. Subordinate (SUB) males, on the other hand, decrease predation risk by adopting cryptic coloration and schooling behavior. We therefore hypothesized that DOMs would show enhanced startle-escape responsiveness to compensate for their increased predation risk. Indeed, behavioral responses to sound clicks of various intensities showed a significantly higher mean startle rate in DOMs compared with SUBs. Electrophysiological recordings from the Mauthner cells (M-cells), the neurons triggering startle, were performed in anesthetized animals and showed larger synaptic responses to sound clicks in DOMs, consistent with the behavioral results. In addition, the inhibitory drive mediated by interneurons (passive hyperpolarizing potential [PHP] cells) presynaptic to the M-cell was significantly reduced in DOMs. Taken together, the results suggest that the likelihood for an escape to occur for a given auditory stimulus is higher in DOMs because of a more excitable M-cell. More broadly, this study provides an integrative explanation of an ecological and social trade-off at the level of an identifiable decision-making neural circuit. 2010.neumeister.jn_.pdf
September 16, 2010, Filed Under: 2011Characterization of the dopaminergic system in the brain of an African cichlid fish, Astatotilapia burtoni Citation: O’Connell LA, Fontenot MR, Hofmann HA. Characterization of the dopaminergic system in the brain of an African cichlid fish, Astatotilapia burtoni. Journal of Comparative Neurology. 519 (1) :75 – 92. Abstract Catecholamines, such as dopamine, are evolutionarily ancient neurotransmitters that play an essential role in mediating behavior. In vertebrates, dopamine is central to the nigrostriatal motor and mesolimbic reward systems. Despite its importance, the distribution of the dopaminergic system has not been well studied in the teleost brain. The African cichlid fish Astatotilapia burtoni has become an important model system in social neuroscience and lends itself to uncovering how social decisions are implemented in the brain. To understand better where dopamine acts to regulate social behavior in this species, we have determined the distribution of putative dopaminergic cells and fibers (by tyrosine hydroxylase immunohistochemistry) and dopamine receptors (by in situ hybridization for the D(1A) and D(2) dopamine receptor subtypes) throughout the forebrain and part of the mesencephalon of A. burtoni. Tyrosine hydroxylase immunoreactivity was evident in several regions of the fore- and midbrain, in support of putative homologies to tetrapods. Additionally, the D(1A) and D(2) receptors were identified in brain regions known to modulate social behavior in other vertebrates, including the proposed teleost homologues of the mammalian amygdalar complex, hippocampus, striatum, preoptic area, anterior hypothalamus, ventromedial hypothalamus, and ventral tegmental area/substantia nigra pars compacta. Tyrosine hydroxylase-immunoreactive fibers as well as D(1A) and D(2) receptor expression overlap almost completely in their distribution. These results significantly extend our understanding of the distribution of the dopaminergic system in the teleost brain and suggest a conserved role of dopamine in modulating behavior across vertebrates. 2011.oconnell.jcn_.dopamine.pdf
September 15, 2010, Filed Under: 2010Behavioural Genomics : An Organismic Perspective Citation: Wong RY, a Hoffmann H. Behavioural Genomics : An Organismic Perspective. Encyclopedia of Life science. :1 – 9. Abstract The behavioural patterns observed in many organisms generally resultfromthe integration ofbothexternaland internal cues. Why do animals behave the way they do? The study of the proximate and ultimate mechanisms underlying animal behaviour tries to answer this ques- tion. Although various approaches have been developed for examining – often quantitatively and with increasing specificity and resolution – the roles genes play in the regulation of behaviour, until recently they were limited to individual candidate genes and often neglected ultim- ate mechanisms. Advances in genomic approaches in recent years have made it possible to examine gene expression patterns (in the brain and elsewhere) on a genomicscale even in nontraditional, yet ecologicallyand evolutionarily important model systems. As behavioural genomics begins to integrate proximate and ultimate mechanisms of animal behaviour, we may finally under- stand why animals behave the way they do. 2010.wong_.els_.pdf
July 2, 2010, Filed Under: 2010Parallel Evolution of opsin gene expression in African cichlid fishes Citation: O’Quin KE, Hofmann CM, Hofmann HA, Carleton KL. Parallel Evolution of opsin gene expression in African cichlid fishes. Molecular Biology and Evolution. 27 (12) :2839 – 2854. Abstract Phenotypic evolution may occur either through alterations to the structure of protein-coding genes or their expression. Evidence for which of these two mechanisms more commonly contribute to the evolution of a phenotype can be garnered from examples of parallel and convergent evolution. The visual system of East African cichlid fishes is an excellent system with which to address this question. Cichlid fishes from Lakes Malawi (LM) and Victoria together exhibit three diverse palettes of coexpressed opsins and several important protein-coding mutations that both shift spectral sensitivity. Here we assess both opsin expression and protein-coding diversity among cichlids from a third rift lake, Lake Tanganyika (LT). We found that Tanganyikan cichlids exhibit three palettes of coexpressed opsins that largely overlap the short-, middle-, and long-wavelength-sensitive palettes of LM cichlids. Bayesian phenotypic clustering and ancestral state reconstructions both support the parallel evolution of the short- and middle-wavelength palettes among cichlids from LT and LM. In each case, these transitions occurred from different ancestors that expressed the same long-wavelength palette. We also identified similar but distinct patterns of correlated evolution between opsin expression, diet, and lens transmittance among cichlids from LT and LM as well. In contrast to regulatory changes, we identified few functional or potentially functional mutations in the protein-coding sequences of three variable opsins, with the possible exception of the SWS1 (ultraviolet) opsin. These results underscore the important contribution that gene regulation can make to rapid phenotypic evolution and adaptation. 2010.oquin_.mbe_.pdf
June 23, 2010, Filed Under: 2010The neuroendocrine action potential. Winner of the 2008 Frank Beach Award in Behavioral Neuroendocrinology Citation: Hofmann HA. The neuroendocrine action potential. Winner of the 2008 Frank Beach Award in Behavioral Neuroendocrinology. Hormones and Behavior [Internet]. 58 (4) :555 – 562. Publisher’s Version Abstract Animals are remarkably well equipped to respond to changes in their environment across different time scales and levels of biological organization. Here, I introduce a novel perspective that incorporates the three main processes the nervous system uses to integrate and process information: electrophysiological, genomic, and neuroendocrine action potentials. After discussing several examples of neuroendocrine action potentials, I lay out the commonalities of these temporally organized responses and how they might be interrelated with electrophysiological activity and genomic responses. This framework provides a novel outlook on longstanding questions in behavioral neuroendocrinology and suggests exciting new avenues for further research that will integrate across disciplines and levels of biological organization. ?? 2010 Elsevier Inc. 2010.hofmann.hb_.pdf
June 1, 2010, Filed Under: 2010Early developmental patterning sets the stage for brain evolution. Citation: Hofmann HA. Early developmental patterning sets the stage for brain evolution. Proceedings of the National Academy of Sciences of the United States of America. 107 (22) :9919 – 9920. 2010.hofmann.pnas_.pdf
May 20, 2010, Filed Under: 2010Distribution of sex steroid hormone receptors in the brain of an african cichlid fish, astatotilapia burtoni Citation: Munchrath LA, Hofmann HA. Distribution of sex steroid hormone receptors in the brain of an african cichlid fish, astatotilapia burtoni. Journal of Comparative Neurology. 518 (16) :3302 – 3326. 2010.munchrath.jcn_.pdf
April 29, 2010, Filed Under: 2010Using comparative genomic hybridization to survey genomic sequence divergence across species: a proof-of-concept from Drosophila. Citation: Renn SCP, Machado HE, Jones A, Soneji K, Kulathinal RJ, Hofmann HA. Using comparative genomic hybridization to survey genomic sequence divergence across species: a proof-of-concept from Drosophila. BMC Genomics [Internet]. 11 :271 – 271. Publisher’s Version Abstract Genome-wide analysis of sequence divergence among species offers profound insights into the evolutionary processes that shape lineages. When full-genome sequencing is not feasible for a broad comparative study, we propose the use of array-based comparative genomic hybridization (aCGH) in order to identify orthologous genes with high sequence divergence. Here we discuss experimental design, statistical power, success rate, sources of variation and potential confounding factors. We used a spotted PCR product microarray platform from Drosophila melanogaster to assess sequence divergence on a gene-by-gene basis in three fully sequenced heterologous species (D. sechellia, D. simulans, and D. yakuba). Because complete genome assemblies are available for these species this study presents a powerful test for the use of aCGH as a tool to measure sequence divergence. 2010.renn_.bmc_.pdf