Genetic analysis of fighting behavior in mice.
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As a result of reciprocal crosses between the SHR rats (spontaneously hypertensive strain) and WKY rats (normotensive strain), two types each of the F1 and F2 hybrids and 4 types of backcrosses were obtained. Analysis of reciprocal differences carries out in these generations for a number of behavioral and physiological traits demonstrated linkage of an hereditary factor affecting expression of potassium appetite with the Y-chromosome. The maternal effect contrary to the action of chromosomal hereditary factors was established for locomotor activity in the peripheral zone of open field. This maternal effect was manifested in the F1 and F2 generations, but not in backcrosses.
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The production of mice with specific deletion of targeted genes (knockouts) has provided a useful tool in understanding the mechanisms underlying behavior. There are many opportunities with this new tool for behavioral neuroendocrinology, specifically, and behavioral biology, generally. Although this genetic technique offers new opportunities to study the mechanisms of behavior, as with all behavioral techniques there are some potential limitations. For example, the products of many genes are essential to normal function, and inactivating the gene may prove lethal or induce gross morphological or physiological abnormalities that can complicate interpretation of discrete behavioral effects. Unexpected compensatory or redundancy mechanisms might be activated when a gene is missing and cloud interpretation of the normal contribution of the gene to behavior. Behavioral tests study the effects of the missing gene (and gene product), not the effects of the gene directly. This conceptual shortcoming can be overcome in the same way that it is overcome in other types of ablation studies, by collecting converging evidence using a variety of pharmacological, lesion, and genetic manipulations. Finally, because mammalian genome mapping is currently focused on mice (Mus musculus), standardized behavioral testing of mice should be adopted. Against those disadvantages are several important advantages to using knockout mice in behavioral research: (1) disabling a gene is often a very precise and "clean" ablation, (2) the effects of the gene product can be abolished without the side-effects of drugs, and (3) genetic manipulations may be the only way to determine the precise role of many endogenous factors on behavior. The use of new inducible knockouts, in which the timing and placement of the targeted gene disruption can be controlled, will be an extremely important tool in behavioral endocrinology research.
Audiogenic seizure (AGS) models of developmental or genetic origin manifest characteristic indices of generalized seizures such as clonus or tonus in rodents. Studies of seizure-resistant strains in which AGS is induced by intense sound exposure during postnatal development provide models in which other neural abnormalities are not introduced along with AGS susceptibility. A critical feature of all AGS models is the reduction of neural activity in the auditory pathways from deafness during development. The initiation and propagation of AGS activity relies upon hyperexcitability in the auditory system, particularly the inferior colliculus (IC) where bilateral lesions abolish AGS. GABAergic and glutaminergic mechanisms play crucial roles in AGS, as in temporal lobe models of epilepsy, and participate in AGS modulatory and efferent systems including the superior colliculus, substantia nigra, basal ganglia and structures of the reticular formation. Catecholamine and indolamine systems also influence AGS severity. AGS models are useful for elucidating the underlying mechanisms for formation and expression of generalized epileptic behaviors, and evaluating the efficacy of modern treatment strategies such as anticonvulsant medication and neural grafting.
Previous work has identified inherent behavioral, neuroendocrine, and biochemical differences among inbred rodent strains that have been related to the animals' differential responsiveness to drugs of abuse or stress. In the present study, we sought to determine (1) whether there are genetic correlations among particular phenotypic traits that differ between a pair of inbred rat strains (Lewis and Fischer 344) or a pair of inbred mouse strains (A/J and C57BL/6J); (2) which of these traits might be amenable to quantitative trait locus analysis; and (3) whether additional behavioral or biochemical differences relevant to drug- or stress-responsiveness could be identified in these strains. Specifically, we measured several behavioral, neuroendocrine, and biochemical traits in parental Lewis and Fischer 344 rats and in 298 members of an F2 intercross population, as well as in parental A/J and C57BL/6J mice and in 11 of the AXB/BXA recombinant inbred mouse strains. Traits measured included exploratory locomotor activity in a novel environment; amphetamine-induced locomotor activity; several specific protein levels in striatal regions, including inhibitory G protein subunits, the dopamine transporter, the Fos family member transcription factor DeltaFosB, and the protein phosphatase inhibitor DARPP-32; and late-afternoon plasma corticosterone concentrations. Each of the traits measured in F2 rats or recombinant inbred mice appears to be influenced by multiple genes, as well as by environmental factors. There were statistically significant, albeit relatively weak, correlations among several traits in an F2 intercross population bred from Lewis and Fischer rats. Among the traits studied in Lewis and Fischer rats, one seemed most amenable to quantitative trait locus analysis: the level of the inhibitory G-protein subunit, Galphai, in the nucleus accumbens. We also found a robust genetic correlation between levels of DeltaFosB and levels of the dopamine transporter in striatal regions in AXB/BXA recombinant inbred mouse strains. While these studies demonstrate the likely complexity of the genetic factors that influence the numerous phenotypes associated with altered responsiveness to drugs of abuse and stress, they represent an initial and necessary step toward identifying specific genetic factors involved.
Artificially selected aggressive (SAL) and non-aggressive (LAL) male house mice were tested in a hexagonal tunnel maze and light-dark preference (LD) box to determine if the bidirectional selection for aggressive behavior leads to a coselection for different levels of trait anxiety. The tunnel maze consists of an open, brightly lit central arena surrounded by a complex system of interconnecting tunnels. As in the LD box, animals which spend less time and are less active in the brightly illuminated section of the maze are considered to have higher anxiety levels. In the tunnel maze, the LAL mice showed more exploration and spent more time in the central arena than the SAL animals, but only during the final 2 min of the 6-min test. This reduced preference for the central arena was not due to general inactivity or a failure of the SAL to find the central arena and indicates a higher level of state anxiety in the aggressive animals. In contrast, no "anxiety-like" differences were found in the LD box, either for the percentage of time spent in the light compartment or for the number of crossings. SAL males actually showed higher levels of moving and rearing, and lower levels of freezing, than did LAL males.
Behavior of nonlinear rats and animals from Wistar and WAG/Rij (with inborn generalized absence epilepsy) strains was examined in the elevated plus-maze and the hole board. WAG/Rij rats demonstrated low exploratory behavior in both tests. In the elevated plus-maze, WAG/Rij rats were more balanced and more anxious than Wistar and nonlinear rats. Administration of ethosuximide completely eliminated spike-wave discharges but did not change behavioral interstrain differences. Since the spike-wave patterns develop in WAG/Rij at the age of 3 months, the behavior of young (2-moth-old) pups from different strains was compared and significant differences were revealed. Correlation between the genetically defined features (spike-wave discharges) and behavioral peculiarities in WAG/Rij rats is supposed.
Genetic study on emigration behavior of Drosophila melanogaster in the Ishinomaki population was conducted with 140 2nd chromosome lines. Fourteen sets of 5X5 partial diallel cross experiments were made to examine the emigration activity of F1 progeny. Emigration activity was scored using the method of Sakai et al. (1958). Additive genetic variance was 0.0377 +/- 0.0069 and dominance variance 0.0076 +/- 0.0032. The average degree of dominance of mildly deleterious genes for emigration activity in an equilibrium population was 0.069 +/- 0.042. The estimated degree of dominance at a gene locus affecting emigration activity was 0.067, which revealed nearly complete dominance for the tendency of heterozygote flies to move from their original place to another. Average degree of dominance of lethal gene for emigration activity was 0.012.
Wind-borne migration, in which migrants ascend to altitudes at which they are transported downwind, has evolved independently in several insect orders. The use of a range of observational techniques, including ground and air-borne radars, has provided new insights into how the migrants' behavior can influence the distance traveled and the degree of dispersal during migration. Simultaneously in recent years, advances in our knowledge of the genetics of migratory potential have provided a basis for understanding how the stochastic effects of the winds on destinations and the pattern of habitat distribution in space and time maintain variation in these traits in populations of wind-borne migrants. This variation, in turn, is an essential factor in the ability of these insects, many of which are important pests, to track often unpredictable changes in the spatial distribution of suitable habitats.
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Most behavior is expressed within social systems, and the genetic analysis of its variance therefore presents theoretical and technical problems that have been sidestepped in most previous research. The dog presents obvious advantages for studying behavioral interactions between genotypes. Two sets of data are summarized that indicate that the magnitude of genetic differences is related to the differentiation of social roles in a competitive situation, whereas similarity of genotypes is an advantage in a situation demanding coordinated activity. Issues concerning the use of correlational techniques to study social behavior are raised.
The Flinders Sensitive Line (FSL) model is considered a genetic animal model of depression. Among other characteristics, FSL rats express stress-induced anhedonia and an abnormal dopaminergic system. Our hypothesis was that FSL rats would show abnormal maternal behaviors, especially reduced motivation to reach and care for pups and reduced licking and non-nutritive contact, based on their anhedonic characteristics. Mother-infant interactions were assessed by time limited observations in FSL and Sprague-Dawley (SD) controls. In study 1, differences were found in consummatory behaviors: FSL dams compared to SD dams showed less licking and significant decrease in non-nutritive contact from the first to the third postpartum weeks. In addition, shorter duration of nursing postures was seen in FSL compared to SD dams in the first week postpartum, and this difference was significantly increased by the third week postpartum. In study 2, after exposure to acute swim stress, differences emerged in appetitive behaviors: latencies to reach and care for pups were longer in FSL dams compared to controls, suggesting a stress-induced motivational deficit in FSL dams. Possible explanations, especially regarding the FSL dams' reward system are discussed.
Epileptiform discharges in 8 electrode waking EEGs at rest and during hyperventilation in 1,057 healthy children aged 6-12 years from an elementary school were studied: Epileptiform discharges, detected in 53 children (5.0%), consisted of centrotemporal spikes (37 cases), generalized spike and slow wave complexes (10 cases), occipital spikes (2 cases), frontal spikes (1 case), and a combination of multiple spike and slow wave complexes and focal spikes (2 cases). The occurrence of a positive past history of febrile convulsions was higher in children with epileptiform discharges (18.9%) than in those without epileptiform discharges (9.4%). Using the Rutter scales for teachers and parents, we compared the emotional and behavioral problems of children with epileptiform EEG discharges with those of children without epileptiform discharges. No statistically significant differences were noted, indicating that the emotional and behavioral problems existing are most probably coincidental and not directly related to the epileptiform discharges. A genetic basis for generalized epileptiform discharges was postulated because the occurrence of generalized discharges in siblings of probands with generalized discharges was higher (4 of 9, 44.4%) than the prevalence in all subjects. However, the occurrence of centrotemporal spikes in the siblings of probands with centrotemporal spikes was not higher (2/38, 5.3%) and an autosomal-dominant genetic factor for centrotemporal spikes in waking EEGs of healthy children could not be confirmed.
OBJECTIVES: To review the data that support the role of genetic factors in the predisposition to suicidal behavior and to examine whether or not these factors are part of the genetic liability to mood disorders. To review molecular genetic studies carried out in suicidal behavior. METHODS: A review of the literature was carried out by means of systematic bibliographic database searches and complemented by searches in the references of relevant publications. RESULTS: There is consistent evidence suggesting that genetic factors play an important role in the predisposition to suicide and suicidal behaviors. Although there is important overlap between suicide and mood disorders, a common genetic liability seems unlikely. It is possible that part of the predisposition to suicide may be transmitted via the presence of impulsive and impulsive-aggressive behaviors. An increasing number of molecular genetic studies have been carried out in subjects with suicidal behavior. There is some support for a role of some genes that code for components of the serotonergic pathway in the etiology of suicidal behavior, but these studies are still preliminary. CONCLUSIONS: Further studies are needed at the epidemiological, clinical and molecular level to better characterize the genetics of suicide. These should control for the presence of behaviors that are considered as part of the phenotypic spectrum of suicide.
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