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PubMed1975

Genetic antecedents of altruistic behavior in Passeriformes.

On the basis of a theory for the establishment and increase of altruistic genes in animal populations a relationship was hypothesized to exist in an avian order between clutch averages (which were considered an index of "genetic investment") and prosocial behavior. The order Passeriformes was used, as clutch sizes were found to vary from one to 11 among the species, and the number of caretakers was also found to vary, falling into four categories: female only, female and male, both plus intraspecies helpers, and interspecies altruists. The positive correlations found in this research tend to support this theory.

Animals↗
PubMed2005

The role of health education and behavior in public health genetics.

This article highlights the important role of health behavior and health education (HBHE) research in public health genetics. Broadly defined, public health genetics is the integration of genetic advancements and technologies in the study and practice of public health. The potential role of HBHE within this area is presented across two intersecting continua--namely, the continuum between research and practice and the continuum between individual/personalized medicine and population health. The authors begin this article with an overview of current issues arising from the use of genetic information to improve the public's health and provide a framework for understanding the multidimensional role of HBHE research in translating genetic research into medical and public health practice. An introduction to the nine articles and two practice notes included in this special issue is also provided to draw attention to the crosscutting themes and issues presented.

Genetic Research↗
PubMed2004

Deficits in sensorimotor gating and tests of social behavior in a genetic model of reduced NMDA receptor function.

Reduced NMDA receptor function is hypothesized to contribute to the pathophysiology of schizophrenia. In order to model chronic and developmental NMDA receptor hypofunction, a mouse line was developed that expresses low levels of the NMDA R1 subunit (NR1) of the NMDA receptor. The present study tested the hypothesis that these NR1 hypomorphic mice would exhibit deficits in sensorimotor and conspecific interactions, analogous to deficits observed in schizophrenic patients. F1 hybrid mice homozygous for the NR1 hypomorphic mutation (NR1 -/-) were generated by crossing heterozygous mice (NR1 +/-) from C57BL/6 and 129 Sv/Ev backgrounds. To assess sensorimotor gating, mice were tested in the paradigm of prepulse inhibition of acoustic startle. The NR1 hypomorphic mice exhibited increased acoustic startle responses and also showed deficits in prepulse inhibition. Startle responses were differentially altered by predator odor exposure in the male NR1 -/- mice, in comparison to control mice. In a test of social affiliation, the wild type mice spent significantly more time investigating a novel mouse in comparison to the NR1 -/- mice. In a resident-intruder test, marked deficits were found in sex-specific aggressive behavior between the wild type and mutant mice. These data support the contention that the NR1 hypomorphic mice exhibit alterations in sensorimotor gating and typical conspecific interactions, reminiscent of behavioral disturbances associated with schizophrenia. The NR1 hypomorphic mice could represent a model system to explore novel treatment and preventative strategies for certain symptoms of schizophrenia.

Agonistic Behavior↗
PubMedDate not supplied

Amelioration of the behavioral phenotype in genetically ataxic mice through bilateral intracerebellar grafting of fetal Purkinje cells.

We have previously applied neural grafting to "Purkinje cell degeneration" mutant mice (gene symbol pcd, mouse chromosome 13), a model of recessively inherited cerebello-olivary atrophy, to create appropriate interactions between wild-type and mutant cells in elucidating gene effects on the involved neuron populations and to address issues of the structural integration of donor Purkinje cells into the disrupted cerebellar loop. Behaviorally, pcd homozygotes manifest ataxic signs beginning at 3-4 wk of age. The functional effects of cerebellar transplants on motor performance have long remained an open question. The aim of the present study was to determine the recovery of motor responses in pcd mutants in a battery of behavioral tasks after bilateral transplantation of cerebellar cell suspensions (prepared from wild-type mice) into the parenchyma of the deep cerebellar nuclei of the hosts, according to a protocol that emphasizes the reconstruction of the missing inhibitory cortico-nuclear projection. With this approach, the denervated deep nuclei of the host receive a new Purkinje axonal innervation; further, most transplanted Purkinje cells end up occupying cortical localities anyway and display a correct dendritic tree orientation toward the pia. Motor coordination and fatigue resistance were assessed in a rotarod treadmill apparatus, a behavioral paradigm useful in studying various brain abiotrophies and treatments, including developmental perturbations of the cerebellar cytoarchitecture. Locomotor activity was quantified by the number of squares mice crossed as they moved about in an open-field matrix. Grafted pcd mice performed significantly better than sham-operated mutants in both of these tasks. Moreover, graft-recipient mice were able to sustain their abdomen above the floor on their limbs during movement, contrasting to the typical lowered, widened stance of sham-operated pcd mutants. These findings clearly demonstrate that bilateral transplants of fetal Purkinje cells have functional effects on motor performance in the pcd model of hereditary cerebellar ataxia.

Animals↗
PubMed1997

Genetic differences in behavioral sensitivity to a neuroactive steroid.

Recent work found that lower endogenous levels of the gamma-aminobutyric acid-agonist, neuroactive steroid 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-THP) may be correlated with increased ethanol withdrawal severity in the selectively bred Withdrawal Seizure-Prone and -Resistant mice. The present studies were conducted to determine whether decreased sensitivity to 3alpha,5alpha-THP was correlated with ethanol withdrawal hyperexcitability in another genetic mouse model, namely the C57BL/6 (B6) and DBA/2 (D2) inbred strains. These strains also differ in ethanol withdrawal severity (D2 >> B6). B6 and D2 male mice were injected with 3alpha,5alpha-THP (0-10 mg/kg i.p.) 15 min before the timed tail vein infusion of pentylenetetrazol. B6 mice were more sensitive than D2 animals to the anticonvulsant effect of 3alpha,5alpha-THP. Subsequent studies measured sensitivity to several of the pharmacological effects of 3alpha,5alpha-THP. B6 and D2 male mice were injected with 3alpha,5alpha-THP (0-32 mg/kg) before testing for locomotor activation (total number of entries) and anxiolysis (percent open arm entries) on the elevated plus maze, muscle relaxation (impairment of forelimb grip strength), ataxia (impairment of Rotarod performance) and seizure susceptibility to pentylenetetrazol. B6 mice were more sensitive than D2 animals to the anxiolytic, locomotor stimulant and anticonvulsant effects of 3alpha,5alpha-THP. In contrast, D2 mice were more sensitive than B6 mice to 3alpha,5alpha-THP-induced muscle relaxation and ataxia. Plasma 3alpha,5alpha-THP levels did not differ in the B6 and D2 mice injected with this steroid, suggesting that the strain differences were not pharmacokinetic. Collectively, the results in selectively bred Withdrawal Seizure-Prone and -Resistant mice and B6 and D2 inbred strains suggest that genetic differences in neuroactive steroid sensitivity and biosynthesis may contribute to ethanol withdrawal severity.

Animals↗
PubMed1991

Are rats with genetic absence epilepsy behaviorally impaired?

Absence seizures in humans are characterized by unresponsiveness to external stimuli and inactivity. However, in typical generalized non-convulsive epilepsy in children, intellectual capacities are considered to be normal. Wistar rats from an inbred strain with spontaneous absence-like seizures were compared with rats from the outbred control strain in various behavioral tasks in order to detect possible impairments related either to the absence epilepsy or to occurrence of spike and wave discharges (SWD). Spontaneous circadian locomotion, exploratory activity in an open field, social interactions with an unfamiliar conspecific and mouse killing behavior were similar in both strains. Avoidance learning in a shuttle box or food reinforced learning in a Skinner test were unimpaired or even improved in epileptic rats. During performance of a learned task either in the Skinner box or in a conditioned sound-bar pressing task, SWD were suppressed in epileptic rats as long as they were working for reinforcement. SWD reappeared when the motivation to perform the task had declined: unresponsiveness to a conditioned stimulus was then observed during SWD. These data are in agreement with observations commonly described in children with typical genetic absence epilepsy.

Aggression↗
PubMed2006

The implications of simultaneous smoking initiation for inferences about the genetics of smoking behavior from twin data.

We examined early social influences across stages of smoking within the context of a twin study using an environmental exposure specific to smoking: whether twins started smoking at the same time ("simultaneous smoking initiation": SSI). We expected that SSI would be a good index of shared social influences on smoking initiation. Rates of SSI were indeed significantly higher in MZ twins and in twins who shared peers and classes, as well as in male twins. With the exception of regular smoking in females, we found no significant difference in estimates of genetic and environmental parameters between SSI and non-SSI pairs for any of the smoking measures that we examined (DSM-IV and Fagerstrom HSI measures of nicotine dependence; DSM-IV nicotine withdrawal; heavy smoking; and in males, regular smoking). For regular smoking in females, allowing for additional shared environmental influences associated with SSI only modestly reduced our estimates of additive genetic variance (56% vs. 68%). These results indicate the important social influences that may occur for smoking initiation do not appear to seriously bias estimates of genetic effects on later stages of smoking.

Adult↗
PubMed2004

Genetic basis of tobacco smoking: strong association of a specific major histocompatibility complex haplotype on chromosome 6 with smoking behavior.

The genetic basis for addiction to tobacco smoking--particularly that of the perception of olfactory stimuli that may be important in reinforcing smoking addiction--is largely unknown. A cluster of genes for olfactory receptors is in close proximity to the MHC region on chromosome 6. Polymorphisms of MHC class III genes (RCCX modules, TNFA promoter polymorphisms) were determined in 101 healthy subjects and 232 coronary artery disease (CAD) patients from Hungary with defined tobacco smoking habits. A highly significant association between ever smoking (past + current smokers) and a specific MHC haplotype was observed (odds ratios = 2.14-4.13; P-values = 0.012 to <0.001). This haplotype is characterized by the presence of C4A null alleles and a solitary short C4B gene linked to the TNF2 allele of the promoter for TNFA gene. This haplotype occurred more frequently in the ever smokers than in the never smokers [odds ratio: 4.97 (1.96-12.62); P = 0.001], and such associations were stronger in women (odds ratio = 13.6) than in men (odds ratio = 2.79). An independent study of complement C4 protein polymorphism and smoking habits in Icelandic subjects (n = 351) yielded similar and confirmative results. Considering the documented link between olfactory stimuli and smoking in females, and the presence of a cluster of odorant receptor genes close to the MHC class I region, our findings implicate a potential role of the MHC-linked olfactory receptor genes in the initiation of smoking.

Adult↗
PubMed2000

Sensitivity to ethanol-induced motor incoordination in 5-HT(1B) receptor null mutant mice is task-dependent: implications for behavioral assessment of genetically altered mice.

Neuromuscular impairment by ethanol likely involves complex effects on balance, gait, muscle strength, and other features of motor coordination. The present experiments showed that relative sensitivity to ethanol-induced motor impairment in serotonin 1B (5-HT(1B)) null mutant and control mice was task dependent. We found that ethanol-treated null mutant mice made fewer missteps on a balance beam than did ethanol-treated wild-type mice, and confirmed a previous finding of their lesser ethanol sensitivity in the grid test. The genotypes did not differ in ethanol sensitivity as measured by the screen test, static dowel, fixed-speed rotarod, accelerating rotarod, grip strength, or loss of righting reflex tests. These experiments suggest that within a behavioral domain, alternative tests of function are not equivalent, so multiple assessment tools should be used to avoid misinterpretation of gene function.

Animals↗
PubMed2003

Genetic influences on smoking behavior and nicotine dependence: a review.

Molecular epidemiologic studies suggest genetic factors in the etiology of smoking behavior. Dopamine receptor genes, transporter genes (serotonin and dopamine), and other genes related to metabolism of nicotine are plausible functional candidate genes. Research examining the role of allelic variation in those genes is being actively pursued with respect to nicotine dependence as well as personality characteristics and mental disorders. Some of these genes were reported to be connected with schizophrenia. Although nicotine dependence itself is one of the mental disorders according to the fourth edition of Diagnostic and Statistical Manual of Mental Disorders and the World Health Organization's International Statistical Classification of Diseases and Related Health Problems-10 nomenclature, the high comorbidity between nicotine dependence and other mental disorders such as schizophrenia or affective disorders has been noted. Therefore, the relationship between those mental disorders and tobacco addiction should be cleared up considering the interactive effect of genetic and environmental factors.

Behavior, Addictive↗
PubMed2006

Deviant peer affiliation and problem behavior: a test of genetic and environmental influences.

This study uses a multitrait, multimethod (MTMM) approach to investigate the genetic and environmental etiologies of childhood deviant peer affiliation (DPA) and problem behavior (PROB). The variability of genetic and environmental estimates by agent and method is also examined. A total of 77 monozygotic and 72 dizygotic twin pairs and each twin's close friend were assessed. The informants included parents, teachers, and twins, and the methods involved questionnaire reports and coder ratings of videotaped dyadic interactions between each twin and their close friend. Twin intraclass correlations and univariate models attributed DPA and PROB to genetic, and shared and nonshared environmental effects. Parameter estimates differed by rater and method, however. Results accentuate the imperative to attend to method effects inherent in MTMM behavioral geneticresearch.

Adolescent↗
PubMed1977

Genetic analysis of phototactic behavior in Drosophila simulans.

Phototaxis mazes have been employed to select photopositive and photonegative strains of Drosophila simulans. The results suggest that phototactic behavior in D. simulans, as in other Drosophila species, is a polygenic trait. Hybridization using divergent strains revealed that the genes controlling negative phototactic behavior in D. simulans are autosomal, as opposed to D. melanogaster in which negative phototactic behavior is known to be very strongly sex-linked.

Animals↗
PubMed2003

Large-scale gene expression profiling of discrete brain regions: potential, limitations, and application in genetics of aggressive behavior.

Many behavioral geneticists are interested in unraveling the molecular mechanisms underlying aggressive behavior. So far, most scientists have based their search for aggression-related genes on a preliminary functional hypothesis. Large-scale gene expression profiling techniques, such as serial analysis of gene expression (SAGE) and DNA microarrays, now enable the screening of expression levels of thousands of genes simultaneously, allowing the identification of new candidate aggression-related genes expressed in brain and thus the generation of new hypotheses. However, expression profiling in the brain is challenging, as brain is a complex heterogeneous tissue where large numbers of genes are expressed and relatively small changes in gene expression occur. In this special issue, we focus on the principles of SAGE and DNA microarrays, as well as their advantages and disadvantages and application to analysis in brain tissue in order to identify aggression-related genes.

Aggression↗
PubMed2006

Behavioral regulation of genetic caste determination in a Pogonomyrmex population with dependent lineages.

The fate of a social insect colony is partially determined by its ability to allocate individuals to the caste most appropriate for the requirements for growth, maintenance, and reproduction. In pairs of dependent lineages of Pogonomyrmex barbatus, the allocation of individuals to the queen or worker caste is constrained by genotype, a system known as genetic caste determination (GCD). In mature GCD colonies, interlineage female eggs develop into sterile workers, while intralineage eggs become reproductively capable queens. Although the population-level consequences of this system have been intensively studied, the proximate mechanisms for GCD remain unknown. To elucidate these mechanisms, we brought newly mated queens into the laboratory and allowed them to establish colonies, nearly half of which unexpectedly produced virgin queens only seven months after colony founding. We genotyped eggs, workers, and the virgin queens from these colonies. Our results showed that queens in young colonies produce both interlineage and intralineage eggs, demonstrating that queens of GCD colonies indiscriminately use sperm of at least two lineages to fertilize their eggs. Intralineage eggs were more frequent in colonies producing virgin queens. These findings suggest that intralineage eggs are predetermined to become queens and that workers may cull these eggs when colonies are not producing queens. Virgin queens produced by young GCD colonies were smaller than field-caught virgin queens, and often had developmental problems. Hence, they are probably nonfunctional and represent an intense resource drain for developing colonies, not a contribution to colony fitness.

Animals↗