The locus ceruleus: a possible neural focus for genetic differences in emotionality

Summary The Maudsley Reactive and Non-Reactive strains have been developed as a model for the study of individual variations in stress-reactivity, and many differences in biobehavioral systems have been found between them. This review discusses limitations of the emotionality construct in accounting for differences between the Maudsley strains and offers an alternative, theoretical approach. Amaral and Sinnamon have proposed that the locus ceruleus (LC) plays a stress-attenuating role in mediating behavioral, physiological and neuroendocrine response to prepotent, emergency-provoking stimuli and, building upon this formulation, it is proposed that the LC has been an important focus for gene action in the Maudsley model. It is suggested that the LC of the Non-Reactive strain is more strongly activated by stressful stimuli than the LC of Reactive rats, and is the basis of many of the behavioral and physiological differences between them. Behavioral and biochemical evidence consistent with this proposition is reviewed. Identification of the LC as a target for gene-action in the Maudsley model has an important advantage. It substitutes variations at a specific anatomic location in the brain for a loosely defined construct like emotionality, and the hypothesis is amenable to empirical tests by a variety of experimental approaches.Supported by MH-39210 from the National Institute of Mental Health to DAB     

Of volatiles and peptides: in search for MHC-dependent olfactory signals in social communication

Genes of the major histocompatibility complex (MHC), which play a critical role in immune recognition, are considered to influence social behaviors in mice, fish, humans, and other vertebrates via olfactory cues. As studied most extensively in mice, the polymorphism of MHC class I genes is considered to bring about a specific scent signature, which is decoded by the olfactory system resulting in an individual-specific reaction such as mating. On the assumption that this signature resides in volatiles, extensive attempts to identify these MHC-specific components in urine failed. Alternatively, it has been suggested that peptide ligands of MHC class I molecules are released into urine and can elicit an MHC-haplotype-specific behavioral response after uptake into the nose by sniffing. Analysis of the urinary peptide composition of mice shows that MHC-derived peptides are present, albeit in extremely low concentrations. In contrast, urine contains abundant peptides which differ between mouse strains due to genomic variations such as single-nucleotide variations or complex polymorphisms in multigene families as well as in their concentration. Thus, urinary peptides represent a real-time sampling of the expressed genome available for sensory evaluation. It is suggested that peptide variation caused by genomic differences contains sufficient information for individual recognition beyond or instead of an influence of the MHC in mice and other vertebrates.     

Cerebral lateralization as a source of interindividual differences in behavior

Cerebral laterality can no longer be considered an exclusively human trait, as over the last 15 years there has been an emergence of data to suggest that animal brains are also lateralized. Morphologic, chemical and behavioral indices of brain asymmetry in the rodent have been reported, and it is suggested that variations in the magnitude and direction of these indices are determined by a complex interaction of genetic, hormonal and experiential factors. Interindividual differences in cerebral laterality have been shown to covary with, or predict, individual differences in spatial behavior and stress reactivity, as well as susceptibility to stress pathology and drug sensitivity. Such findings suggest that it is possible to study individual differences in lateralized brain function through the use of animal models.     

Genetic determinants of individual differences in avoidance learning: behavioral and endocrine characteristics

Bidirectional genetic selection for good and poor active avoidance learning in a shuttle box has been carried out in three independent laboratories using remarkably similar discrete-trial training procedures. The resulting strains are known as the Roman High and Low Avoidance (RHA and RLA), the Syracuse High and Low Avoidance (SHA and SLA) and the Australian High and Low Avoidance (AHA and ALA) strains, respectively. An additional unidirectionally selected strain, known as the Tokai High Avoider (THA) strain was developed in Japan using a free-operant Sidman avoidance procedure in a Skinner box. This paper reviews the selection of the Syracuse strains, enumerates the various behavioral and endocrine characteristics of the strains, and compares them to the other similarly selected strains. The behavioral work suggests that genetic selection from diverse breeding stocks has resulted in common characteristics that differentiate the strains in the emotional, not learning, domain. The endocrine data, however, are somewhat at odds. The Syracuse strains differentiate one way with respect to endocrine function, and the Roman strains differentiate in the opposite way. We suggest, therefore, that the endocrine correlates are not tightly linked to the avoidance genotype. Genetic analysis of all of the selected strains for both the avoidance phenotype and the endocrine correlates will be needed to test this hypothesis.     

Genetic determinants of individual differences in avoidance learning: Behavioral and endocrine characteristics

Bidirectional genetic selection for good and poor active avoidance learning in a shuttle box has been carried out in three independent laboratories using remarkably similar discrete-trial training procedures. The resulting strains are known as the Roman High and Low Avoidance (RHA and RLA), the Syracuse High and Low Avoidance (SHA and SLA) and the Australian High and Low Avoidance (AHA and ALA) strains, respectively. An additional unidirectionally selected strain, known as the Tokai High Avoider (THA) strain was developed in Japan using a free-operant Sidman avoidance procedure in a Skinner box. This paper reviews the selection of the Syracuse strains, enumerates the various behavioral and endocrine characteristics of the strains, and compares them to the other similarly selected strains. The behavioral work suggests that genetic selection from diverse breeding stocks has resulted in common characteristics that differentiate the strains in the emotional, not learning, domain. The endocrine data, however, are somewhat at odds. The Syracuse strains differentiate one way with respect to endocrine function, and the Roman strains differentiate in the opposite way. We suggest, therefore, that the endocrine correlates are not tightly linked to the avoidance genotype. Genetic analysis of all of the selected strains for both the avoidance phenotype and the endocrine correlates will be needed to test this hypothesis.Preparation of this paper was supported by research grant MH-39230-3 from the National Institute of Mental Health.     

Comparison of soluble antigens of 2 cultured clones, of different age, from the same strain of a flagellate parasite: Trichomonas vaginalis Donné, 1837]

Antigenic analysis released indications that there seemed to be a qualitative difference between two clones (A2, A3) as well as between a young clone A2 and an old one (the latter having been in culture for 12 months) both of them originating from the same initial clone. Such differences are reduced to quantitative level by the results of cross absorptions. Antigenic variations mentioned by the previous authors are to be questioned.     

Mouse models for human intestinal microbiota research: a critical evaluation

Since the early days of the intestinal microbiota research, mouse models have been used frequently to study the interaction of microbes with their host. However, to translate the knowledge gained from mouse studies to a human situation, the major spatio-temporal similarities and differences between intestinal microbiota in mice and humans need to be considered. This is done here with specific attention for the comparative physiology of the intestinal tract, the effect of dietary patterns and differences in genetics. Detailed phylogenetic and metagenomic analysis showed that while many common genera are found in the human and murine intestine, these differ strongly in abundance and in total only 4% of the bacterial genes are found to share considerable identity. Moreover, a large variety of murine strains is available yet most of the microbiota research is performed in wild-type, inbred strains and their transgenic derivatives. It has become increasingly clear that the providers, rearing facilities and the genetic background of these mice have a significant impact on the microbial composition and this is illustrated with recent experimental data. This may affect the reproducibility of mouse microbiota studies and their conclusions. Hence, future studies should take these into account to truly show the effect of diet, genotype or environmental factors on the microbial composition.     

The genetic and evolutionary basis of colour variation in vertebrates

Variation in pigmentation is one of the most conspicuous phenotypic traits in vertebrates. Although mammals show less variation in body pigmentation than other vertebrate groups, the genetics of colour determination and variation is best understood for them. More than 150 genes have been identified that influence pigmentation, and in many cases, the cause for variation in pigmentation has been identified down to the underlying nucleotide changes. These studies show that while some genes are often responsible for deviating pigmentation, similar or almost identical phenotypes even in the same species may be due to mutations in different genes. In this review we will first discuss the current knowledge about the genes and their functions underlying the biochemical pathways that determine pigmentation and then give examples where the mutations responsible for colour variation have been determined. Finally, we will discuss potential evolutionary causes for and consequences of differences in pigmentation between individuals.     

Signaling in the Chemosensory Systems

The small nematode Caenorhabditis elegans lives in the soil, where mechanical, thermal and most of all chemical stimuli strongly influence its behavior. Here we briefly review how chemical sensitivity is organized at the cellular and molecular level in this organism. C. elegans has less than 40 chemosensory neurons. With few exceptions each neuron senses more than one substance and each substance is sensed by more than one neuron. At the molecular level, as in other organisms, also in C. elegans, seven transmembrane G-protein-coupled receptors (GPCRs), heterotrimeric G proteins, cyclic nucleotidegated ion channels, TRP channels and Ca++ play crucial roles in chemical sensitivity. An unusual feature, possibly due to C. elegans's strong dependence on chemical cues, is the very large number of GPCR chemoreceptor genes (1300-1700) coded in its genome. Genetic approaches have also allowed the identification of new molecules involved in chemical sensitivity that would not have been discovered otherwise. In addition to the basic factors involved in primary signalling, the studies in C. elegans have revealed a network of regulatory pathways and molecules suggesting that fine modulation of the responsiveness of neurons is important, possibly to allow worms to negotiate a continuously changing environment. The experimental versatility of C. elegans has made it possible, in many cases, to determine precisely in which neuron a given molecule or pathway is required and for which biological response. This type of information can contribute to the general field of sensory signalling because it provides correlations between the biochemical properties of molecules and their cellular functions and between these and the in vivo behavioral responses of the animal.     

The AA and ANA rat lines, selected for differences in voluntary alcohol consumption

The offspring of rats that voluntarily select larger quantities of alcohol are heavier consumers of alcohol than the offspring of rats that tend to avoid it. Such selective breeding, repeated over many generations, was used to develop the AA (Alko, Alcohol) line of rats which prefer 10% alcohol to water, and the ANA (Alko, Non-Alcohol) line of rats which choose water to the virtual exclusion of alcohol. In addition to demonstrating the likely role of genetic factors in alcohol consumption, these lines have been used to find behavioral, metabolic, and neurochemical correlates of differential alcohol intake. Some of the line differences that have been found involve the reinforcing effects of ethanol, the changes in consumption produced by alcohol deprivation and nutritional factors, the behavioral and adrenal monoamine reactions to mild stress, the development of tolerance, the accumulation of acetaldehyde during ethanol metabolism, and the brain levels of serotonin. It is hoped that these studies will lead to a better understanding of the genetically-determined mechanisms that influence the selection of alcohol.     

The AA and ANA rat lines,selected for differences in voluntary alcohol consumption

Summary The offspring of rats that voluntarily select larger quantities of alcohol are heavier consumers of alcohol than the offspring of rats that tend to avoid it. Such selective breeding, repeated over many generations, was used to develop the AA (Alko, Alcohol) line of rats which prefer 10% alcohol to water, and the ANA (Alko, Non-Alcohol) line of rats which choose water to the virtual exclusion of alcohol. In addition to demonstrating the likely role of genetic factors in alcohol consumption, these lines have been used to find behavioral, metabolic, and neurochemical correlates of differential alcohol intake. Some of the line differences that have been found involve the reinforcing effects of ethanol, the changes in consumption produced by alcohol deprivation and nutritional factors, the behavioral and adrenal monoamine reactions to mild stress, the development of tolerance, the accumulation of acetaldehyde during ethanol metabolism, and the brain levels of serotonin. It is hoped that these studies will lead to a better understanding of the genetically-determined mechanisms that influence the selection of alcohol.     

Forecasting realized volatility of oil futures market: A new insight

In this study we propose several new variables, such as continuous realized semi‐variance and signed jump variations including jump tests, and construct a new heterogeneous autoregressive model for realized volatility models to investigate the impacts that those new variables have on forecasting oil price volatility. In‐sample results indicate that past negative returns have greater effects on future volatility than that of positive returns, and our new signed jump variations have a significantly negative influence on the future volatility. Out‐of‐sample empirical results with several robust checks demonstrate that our proposed models can not only obtain better performance in forecasting volatility but also garner larger economic values than can the existing models discussed in this paper.     

Geopsychology and geopsychopathology: mental processes and disorders associated with geochemical and geophysical factors

Temporal and regional variations in psychological processes have been associated with three geological factors. They are geochemical profiles, geomagnetic variations, and tectonic stresses. In the geochemical domain, copper, aluminum, zinc, and lithium may influence the incidence of thought disorders such as schizophrenia and senile dementia. These common elements are found in many soils and ground water. Geomagnetic variations have been correlated with enhanced anxiety, sleep disturbances, altered moods, and greater incidences of psychiatric admissions. The effects are usually brief but pervasive. Transient and very local epidemics of bizarre and unusual behaviors are sociological phenomena that sometimes precede increases in earthquake activity within a region; they have been hypothesized to be associated with tectonic strain. Many of the contemporary correlations between geological factors and human behavior are also apparent within historical data. The effects of geophysical and geochemical factors upon human behavior are not artifactual, but they are complex and often not detected by the limited scope of most studies.     

Modelling and representing: An artefactual approach to model-based representation

The recent discussion on scientific representation has focused on models and their relationship to the real world. It has been assumed that models give us knowledge because they represent their supposed real target systems. However, here agreement among philosophers of science has tended to end as they have presented widely different views on how representation should be understood. I will argue that the traditional representational approach is too limiting as regards the epistemic value of modelling given the focus on the relationship between a single model and its supposed target system, and the neglect of the actual representational means with which scientists construct models. I therefore suggest an alternative account of models as epistemic tools. This amounts to regarding them as concrete artefacts that are built by specific representational means and are constrained by their design in such a way that they facilitate the study of certain scientific questions, and learning from them by means of construction and manipulation.     

Behavioral and neuronal mechanisms of cricket phonotaxis

Summary The auditory communication of crickets provides a model system for the analysis of the neuronal mechanisms underlying complex behavior. The song of male crickets attracts females. The necessary and sufficient parameter of the song for the female phonotaxis has been determined by a quantified behavioral analysis. Neuronal correlates of this pattern recognition exist in the cricket brain and give rise to a hypothesis on the mechanism of song pattern recognition. Causal relationships between the orientation of a cricket during phonotaxis and the activity of single identified neurons were found by monitoring and deactivating single neurons during behavior. The different roles of various identifield neurons for sound localization have been tested by this method. The plasticity of the auditory system at both the behavioral and at the neuronal level has been studied after ampytation of one ear, and a mechanism for sound localization with only one ear is proposed.     

Genetic validation of aDrosophila learning task

Summary 4 inbred strains ofDrosophila melanogaster and crosses between them were tested in 2 types of multiple-choice T-maze. It is suggested that genetic analysis can distinguish learning from other behaviours implicated in maze performance. Directional dominance for high performance, which is characteristic of learning in many species, was found only for those aspects of behaviour previously hypothesised as involving learning.     

Geopsychology and geopsychopathology: Mental processes and disorders associated with geochemical and geophysical factors

Summary Temporal and regional variations in psychological processes have been associated with three geological factors. They are geochemical profiles, geomagnetic variations, and tectonic stresses. In the geochemical domain, copper, aluminum, zinc, and lithium may influence the incidence of thought disorders such as schizophrenia and senile dementia. These common elements are found in many soils and ground water. Geomagnetic variations have been correlated with enhanced anxiety, sleep disturbances, altered moods, and greater incidences of psychiatric admissions. The effects are usually brief but pervasive. Transient and very local epidemics of bizarre and unusual behaviors are sociological phenomena that sometimes precede increases in earthquake activity within a region; they have been hypothesized to be associated with tectonic strain. Many of the contemporary correlations between geological factors and human behavior are also apparent within historical data. The effects of geophysical and geochemical factors upon human behavior are not artifactual, but they are complex and often not detected by the limited scope of most studies.     

What’s so special about model organisms?

This paper aims to identify the key characteristics of model organisms that make them a specific type of model within the contemporary life sciences: in particular, we argue that the term “model organism” does not apply to all organisms used for the purposes of experimental research. We explore the differences between experimental and model organisms in terms of their material and epistemic features, and argue that it is essential to distinguish between their representational scope and representational target. We also examine the characteristics of the communities who use these two types of models, including their research goals, disciplinary affiliations, and preferred practices to show how these have contributed to the conceptualization of a model organism. We conclude that model organisms are a specific subgroup of organisms that have been standardized to fit an integrative and comparative mode of research, and that it must be clearly distinguished from the broader class of experimental organisms. In addition, we argue that model organisms are the key components of a unique and distinctively biological way of doing research using models.     

Model-as-replica,model-as-instrument: Representational power and contextual versatility in animal models

Existing scholarship on animal models tends to foreground either of the two major roles research organisms play in different epistemic contexts, treating their representational and instrumental roles separately. Based on an empirical case study, this article explores the changing relationship between the two epistemic roles of a research organism over the span of a decade, while the organism was used to achieve various knowledge ends. This rat model was originally intended as a replica of human susceptibility to cardiac arrest. In a fortunate stroke of serendipity, however, the experimenters detected the way mother-infant interactions regulated the pups’ resting cardiac rate. This intriguing outcome thus became the model’s new representational target and began driving the development of an experimental system. Henceforth, the model acquired an instrumental function, serving to detect and measure system-specific differences. Its subsequent development involved creating stimulus-response measures to explain and theorize those differences. It was this instrumental use of the model that pushed the experimenters into unchartered territory and conferred to the model an ability to adapt to varied epistemic contexts. Despite the prominence of this instrumental role, however, the model’s representational power continued to guide research. The model’s representational target was widened beyond heart rate to reflect other functional phenomena, such as behavioral activity and sleep/wake rhythm. The rat model was thus transformed from an experimental organism designed to instantiate cardiac regulation to a model organism taken to represent the development of a whole, intact animal under the regulatory influence of maternal care. This article examines this multifaceted transformation within the context of the salient shifts in modeling practice and variations in the model’s representational power. It thus explores how the relationship between the representational and instrumental uses of the model changed with respect to the varying exigencies of the investigative context, foregrounding its contextual versatility.