The mathematical theory of group selection. I. Full solution of a nonlinear Levins E = E(x) model.
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Animals↗
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A genotype-dependent hippocampal dynorphinergic mechanism controls mouse exploration.
Following microinjections with two dilutions of anti-dynorphin B antiserum into the hippocampal CA3 region, adult male mice from the inbred strains DBA/2 and C57BL/6 were individually tested for various exploratory behaviors in a novel environment and compared to preimmune serum control animals. Treatment augmented vertically-oriented exploratory acts in strain DBA/2 and reduced the scores in strain C57BL/6 so that strain differences originally present between the controls were reversed or eliminated after antiserum. These opposite effects indicate that a hippocampal dynorphinergic mechanism is involved in the regulation of novelty-induced behavior in mice and that its modulatory function depends on the genotype. It is concluded that DBA/2 animals exposed to novelty, as compared to C57BL/6, are characterized by an over-release of hippocampal dynorphin B which is neutralized in part by small amounts of antibody.
Animals↗
Differential inhibition of synaptosomal accumulation of [3H]-monoamines by cocaine, tropacocaine and amphetamine in four inbred strains of mice.
The relative ability of cocaine, tropacocaine and amphetamine to inhibit the uptake of [3H]norepinephrine (NE), [3H]dopamine (DA) and [3H]5-hydroxytryptamine (5HT) was examined in whole brain synaptosomes from BALB, C3H, C57BL and DBA inbred mouse strains. With inhibition of [3H]NE uptake, synaptosomes from BALB and C57 mice were substantially more sensitive to cocaine inhibition than those from DBA or C3H. Moreover, with BALB and C57 tissue, amphetamine was as potent as cocaine, whereas with C3H and DBA, amphetamine and tropacocaine were much less potent inhibitors of [3H]NE uptake. With respect to [3H]DA accumulation, synaptosomes from BALB, C57 and DBA were equally sensitive to cocaine inhibition, while C3H synaptosomes were significantly less sensitive. In each of the four strains, amphetamine was more potent than cocaine, and tropacocaine far less potent. The relative potencies of the three drugs varied significantly among the four strains. With [3H]5HT accumulation, synaptosomes from DBA were exquisitely sensitive to cocaine inhibition, followed by BALB and lastly by C57 and C3H. In each of these strains, amphetamine and tropacocaine were equipotent at [3H]5HT inhibition, and less potent than cocaine. The results suggest that there are pronounced genetic differences in sensitivity to monoamine uptake inhibition by cocaine, which may arise from genetic differences in either carrier topology or other site of cocaine interaction. The results further suggest that genetic behavioral differences to cocaine and amphetamine may involve complex neurotransmitter interactions.
Amphetamine↗
Multivariate analysis of familial and non-familial influences for commonality in drug use.
A multivariate behavioral genetic analysis of common legal drug usage was performed on data from 238 Swedish families. By calculating cross-covariances between parents and offspring for pairs of traits, familial and non-familial correlations were computed to determine the extent to which pairs of measures share the same familial and non-familial influences. Factor analyses resulted in a 3- and a 2-factor solution for the familial and non-familial correlations, respectively. This suggests that familial and non-familial influences for drug usage are structured differently. If replicable, these results also suggest that the phenotypic structure reflects familial factors more than non-familial influences.
Adult↗
The relevance to clinical care of recent research in neurobiology.
Progress continues to be made in clarifying neurobiological factors in alcoholism and other chemical dependencies. Research in animal behavioral genetics and human genetics has revealed substantial genetic predispositions for some cases of alcoholism. Studies of neurotransmitters suggest that some alcoholics may have antecedent deficiencies in one or more important neurochemical systems. Cocaine dependence is considered to be related to biphasic change in dopaminergic neurons and receptor systems. Condensation products such as salsolinol, tetrahydropapaveroline, and beta carbolines can alter alcoholic preference and motivate heavy ethanol consumption in animals. However, hypothesized theoretical mechanisms underlying such increased drinking with infusions of condensation products are unclear and may require revision. New pharmacological treatments stemming from advances in neurobiological research have been applied successfully to treatment of withdrawal states, but none have been demonstrated to be appropriate for long-term maintenance of abstinence.
Alcoholism↗
The effects of ethanol on exploration in DBA/2 and C57Bl/6 mice.
The effect of ethanol (0.8, 1.6, and 2.4 g/kg) was assessed on the behavior of DBA/2 and C57Bl/6 mice in a holeboard test. Ethanol caused a dose-related decrease in the locomotor activity of the C57Bl/6 mice, and the highest dose also significantly decreased exploratory head-dipping. In contrast ethanol significantly increased the locomotor activity of DBA/2 mice. Only the lowest dose, however, significantly increased exploratory head-dipping, and the highest dose caused a marked decrease in exploration. These results emphasize the importance of distinguishing between the effects of ethanol on locomotor and exploratory activities.
Animals↗
Mouse behavioral tasks relevant to autism: phenotypes of 10 inbred strains.
Three defining clinical symptoms of autism are aberrant reciprocal social interactions, deficits in social communication, and repetitive behaviors, including motor stereotypies and insistence on sameness. We developed a set of behavioral tasks designed to model components of these core symptoms in mice. Male mice from 10 inbred strains were characterized in assays for sociability, preference for social novelty, and reversal of the spatial location of the reinforcer in T-maze and Morris water maze tasks. Six strains, C57BL/6J, C57L/J, DBA/2J, FVB/NJ, C3H/HeJ, and AKR/J, showed significant levels of sociability, while A/J, BALB/cByJ, BTBR T(+)tf/J, and 129S1/SvImJ mice did not. C57BL/6J, C57L/J, DBA/2J, FVB/NJ, BALB/cByJ, and BTBR T(+)tf/J showed significant preference for social novelty, while C3H/HeJ, AKR/J, A/J, and 129S1/SvImJ did not. Normal scores on relevant control measures confirmed general health and physical abilities in all strains, ruling out artifactual explanations for social deficits. Elevated plus maze scores confirmed high anxiety-like behaviors in A/J, BALB/cByJ, and 129S1/SvImJ, which could underlie components of their low social approach. Strains that showed high levels of performance on acquisition of a T-maze task were also able to reach criterion for reversal learning. On the Morris water maze task, DBA/2J, AKR/J, BTBR T(+)tf/J, and 129S1/SvImJ failed to show significant quadrant preference during the reversal probe trial. These results highlight a dissociation between social task performance and reversal learning. BTBR T(+)tf/J is a particularly interesting strain, displaying both low social approach and resistance to change in routine on the water maze, consistent with an autism-like phenotype. Our multitask strategy for modeling symptoms of autism will be useful for investigating targeted and random gene mutations, QTLs, and microarray analyses.
Animals↗
Identification of first candidate genes for creativity: a pilot study.
Studies from behavioral genetics have demonstrated the high heritability of intelligence. However, the endeavor to detect the genes forming the molecular basis of intelligence has been rather unsuccessful until now. Pharmacological studies have demonstrated the influence of the dopaminergic (DA) and the serotonergic (5-HT) system on subcomponents of cognitive functioning, and first studies from molecular genetics have demonstrated that genes related to the DA metabolism are associated with mental abilities. However, candidate genes for creativity have not been identified so far. Therefore, the influence of the catechol-O-methyltransferase (locus: COMT VAL158MET) gene and the dopamine D2 receptor gene (locus: DRD2 TAQ IA) on creativity was tested in addition to a serotonergic gene, TPH1 (locus: TPH-A779C), in a sample of N = 92 healthy Caucasian subjects while controlling for intelligence. Results showed that the DRD2 gene and the TPH gene were both associated with total creativity, explaining 9% of the variance, while COMT was not related to creativity at all. With respect to the subcomponents, the A1+ allele of DRD2 was related to higher verbal creativity as compared to the A1- allele, and carriers of the A allele of TPH1 showed significantly higher scores in figural and in numeric creativity, indicating that the two gene loci discriminate between higher cortical functions according to the organization of cognitive functions in the respective hemispheres.
Adolescent↗
The C. elegans thermosensory neuron AFD responds to warming.
The mechanism of temperature sensation is far less understood than the sensory response to other environmental stimuli such as light, odor, and taste. Thermotaxis behavior in C. elegans requires the ability to discriminate temperature differences as small as approximately 0.05 degrees C and to memorize the previously cultivated temperature. The AFD neuron is the only major thermosensory neuron required for the thermotaxis behavior. Genetic analyses have revealed several signal transduction molecules that are required for the sensation and/or memory of temperature information in the AFD neuron, but its physiological properties, such as its ability to sense absolute temperature or temperature change, have been unclear. We show here that the AFD neuron responds to warming. Calcium concentration in the cell body of AFD neuron is increased transiently in response to warming, but not to absolute temperature or to cooling. The transient response requires the activity of the TAX-4 cGMP-gated cation channel, which plays an essential role in the function of the AFD neuron. Interestingly, the AFD neuron further responds to step-like warming above a threshold that is set by temperature memory. We suggest that C. elegans provides an ideal model to genetically and physiologically reveal the molecular mechanism for sensation and memory of temperature information.
Animals↗
Mate similarity for substance dependence and antisocial personality disorder symptoms among parents of patients and controls.
UNLABELLED: Substance dependence (SD) and antisocial personality disorder (ASPD) are highly comorbid and aggregate in families. Mating assortment may be an important process contributing to this familial aggregation. HYPOTHESIS: Symptom counts of substance dependence, antisocial personality disorder, and retrospectively assessed conduct disorder (CD) will be correlated significantly among parents of youth in treatment for substance use and conduct problems and, separately, among parents of community controls. METHODS: We examined SD, ASPD, and CD among 151 pairs of parents of adolescents in treatment for substance use and conduct problems, and in 206 pairs of parents of control subjects. RESULTS: For average dependence symptoms (ADS) (the sum of across-drug substance dependence symptoms divided by the number of substance categories meeting minimum threshold use) mother-father correlations were 0.40 for patients and 0.28 for controls. Mother--father correlations for ASPD symptom count were 0.33 for patients and 0.26 for controls and for CD symptom count were 0.31 for patients (all P < 0.01) and 0.10 for controls (P = 0.14). CONCLUSIONS: Spousal correlations for ADS and ASPD, suggest substantial non-random mating. Results support gender differences in homogamy for SD. Behavior genetic studies of these disorders need to account for assortment to avoid biases in estimates of genetic and environmental effects.
Adult↗
Neurobiological basis of depression: an update.
The past 5 years have seen unprecedented advances in our knowledge about the neurobiology of depression. Significant breakthroughs have been made in genomics, imaging, and the identification of key neural systems involved in cognition, emotion, and behavior. In addition, novel targets have been identified for the development of new pharmacological and behavioral treatments. Genetic variations associated with most mental disorders are being identified, and reliable tests for early detection of risk and disease are now on the horizon. New neurobiological concepts have emerged, as they relate to these advances in mental health research such as the serotonin transporter receptor, a genetic variant of which doubles the risk of depression. Brain neurochemicals, including neurotropic factors (implicated in several mental disorders), and anatomical studies involving imaging of the amygdala and the hippocampus and prefrontal cortex are now at the forefront. Several brain neurotransmitters systems: glutamate, gamma -aminobutyric acid, serotonin, norepinephrine, and dopamine have been implicated in depression and mania. These transmitter systems, as well as other neurochemical systems such as membrane-bound signal transduction systems and intracellular signaling systems that modulate gene transcription and protein synthesis, play an important role in the etiology of depression. This new knowledge is expected to provide important clues for the development of selective pharmacological interventions. Neuroimaging studies of depressed patients have shown several abnormalities of regional cerebral blood flow and glucose metabolism--a surrogate of neuronal function--in various brain regions, including the limbic cortex, the prefrontal cortex, the hippocampus, the amygdala, and the anterior cingulate cortex. At this time, a considerable amount of new information is converging--derived from animal models of mood disorders, genetics, basic behavioral research, and neuroscience. It is inevitable that the next step in this progression will be the integration of these basic advances in clinical management and the application of this new information in the context of the depressed patient.
Animals↗
Wistar rats with high versus low rearing activity differ in radial maze performance.
Substantial work has shown that rats although identical in stock, sex, age, and housing conditions can differ considerably in terms of behavior and physiology. Such individual differences, which can be detected by specific behavioral screening tests, are rather stable, that is, they probably reflect a behavioral disposition or trait. Here, we asked whether and how such differences might affect performance in a task of spatial learning and memory, the radial maze. As in our previous work, we used the degree of rearing activity in a novel open field to assign male adult outbred Wistar rats into those with high versus low rearing activity (HRA/LRA rats). They were then tested in a plus-maze for possible differences in anxiety-related behavior. Finally, and most importantly, they were food deprived and underwent maze training using an 8-arm radial maze with four non-baited and four baited arms. One of these arms consistently contained a larger bait size than the other three. In the open field, HRA rats not only showed more rearing behavior, but also more locomotor activity than LRA rats. In the plus-maze, HRA rats again showed more locomotion, but did not differ in open arm time or percentage of open arm entries, that is, conventional measures of anxiety-related behavior. In the radial maze, HRA rats consistently needed less time to consume all pellets than LRA rats, which was due to faster locomotion on the arms and less time spent at the food pits (especially in baited arms) of HRA rats. During the initial days of training, they were also more efficient in obtaining all food pellets available. Furthermore, HRA rats visited more arms and made relatively less reference memory errors than LRA rats. This allowed them to forage food quickly, but was paralleled by more working memory errors than in LRA rats. In general, working memory errors were more frequent in the arm with the large bait size, but there were no indications that HRA and LRA rats responded differently dependent on reward size. Finally, LRA rats lost slightly more weight than HRA rats during the period of food deprivation. These results are discussed with respect to the role of cognitive and motivational mechanisms, which as subject-inherent factors can contribute substantially to inter-individual variability in the radial maze.
Analysis of Variance↗
John Maynard Smith and evolutionary game theory.
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Animals↗
Asymmetric population games and the legacy of Maynard Smith: From evolution to game theory and back?
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Animals↗
John Maynard Smith and recombination.
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Animals↗
Determination of volatile anesthetics isoflurane and enflurane in mouse brain tissues using gas chromatography-mass spectrometry.
INTRODUCTION: A method for determination of the volatile anesthetics, isoflurane, and enflurane in mouse brain tissues using headspace gas chromatography-mass spectrometry (GC-MS) is described. METHODS: Halothane was used as internal standard (I.S.). Brain samples were completely homogenized in ice-cold water and isoflurane, enflurane, and I.S. were extracted with headspace. One milliliter of headspace gas was injected onto the GC-MS and separation was achieved by using porous layer open tubular (PLOT) capillary column with a solid stationary phase (GSC). As a result, isoflurane, enflurane, and halothane were cleanly separated. RESULTS: The method demonstrated satisfactory recovery (72% and 76% for isoflurane and enflurane, respectively) and linear calibration ranges of 0.015-2.20 and 0.0152-3.94 microg/sample for isoflurane and enflurane, respectively. Reproducibility calculated as CV% was 3.3-3.9% for all intraday and interday determinations. The procedure was applied for quantitation of isoflurane and enflurane in about 300 mouse brain samples for genetic behavioral study. DISCUSSION: The method was achieved and shown to be effective.
Anesthetics, Inhalation↗
EEG and ERP profiles in the high alcohol preferring (HAP) and low alcohol preferring (LAP) mice: relationship to ethanol preference.
Neurophysiological measures, such as decreased P300 amplitude and altered EEG alpha activity, have been associated with increased alcoholism risk. The purpose of the present study was to extend the assessment of the neurophysiological indices associated with alcohol consumption to a recently developed mouse model of high ethanol consumption, the first replicate line of high alcohol preferring (HAP-1) and low alcohol preferring (LAP-1) mice. Male HAP-1, LAP-1, and HS mice from the Institute for Behavioral Genetics at the University of Colorado Health Science Center (i.e., HS/Ibg mice) were implanted with cortical electrodes. EEG activity, and event related potentials (ERPs) were then examined. Following electrophysiological assessment, ethanol preference was assessed to examine the relationship between neurophysiological indices and ethanol consumption. EEG analyses revealed that HAPs and HS/Ibgs had greater peak frequency in the 2-4-Hz band and lower peak frequency in the 6-8- and 1-50-Hz bands of the cortical EEG compared to LAPs. Compared to HAPs, LAPs and HS/Ibgs had decreased peak EEG frequency in the 8-16-Hz band. Decreased parietal cortical power from 8 to 50 Hz was associated with high initial ethanol preference in HAP mice. In regards to ERPs, P1 amplitude was greater in HAPs compared to both LAPs and HS/Ibgs and the P3 latency in LAPs was decreased compared to both HAPs and HS/Ibgs. As expected, HAPs consumed more ethanol and had higher ethanol preference than LAPs and HS/Ibgs. There were no significant differences in ethanol intake or preference between HS/Ibgs and LAPs. These data indicate that selective breeding of the HAP and LAP lines has resulted in the divergence of EEG and ERP phenotypes. The differences observed suggest that increased cortical P1 amplitude and altered cortical EEG activity in the 8-50-Hz frequency range may be neurophysiological 'risk factors' associated with high ethanol consumption in mice. Decreased P3 latency in LAPs compared to HAPs and HS/Ibgs mice may be a 'protective factor'.
Acoustic Stimulation↗
Model-based fault diagnosis in continuous dynamic systems.
Traditional fault detection and isolation methods are based on quantitative models which are sometimes difficult and costly to obtain. In this paper, qualitative bond graph (QBG) reasoning is adopted as the modeling scheme to generate a set of qualitative equations. The QBG method provides a unified approach for modeling engineering systems, in particular, mechatronic systems. An input-output qualitative equation derived from QBG formalism performs continuous system monitoring. Fault diagnosis is activated when a discrepancy is observed between measured abnormal behavior and predicted system behavior. Genetic algorithms (GA's) are then used to search for possible faulty components among a system of qualitative equations. In order to demonstrate the performance of the proposed algorithm, we have tested it on a laboratory scale servo-tank liquid process rig. Results of the proposed model-based fault detection and diagnosis algorithm for the process rig are presented and discussed.
Journal Article↗