Texture of locomotor path: a replicable characterization of a complex behavioral phenotype.

A database of mouse locomotor path in spatial tests can be used to search in silico for behavioral measures that better discriminate between genotypes and are more replicable across laboratories. In this study, software for the exploration of exploration (SEE) was used to search a large database for a novel behavioral measure that would characterize complex movement paths. The database included mouse open-field behavior assessed in 3 laboratories, 7 inbred strains, several pharmacological treatments and hundreds of animals. The new behavioral measure, "path texture", was characterized using the local curvature of the path (the change of direction per unit distance, in degrees/cm) across several spatial scales, starting from scales smaller than the animal's body length and up to the scale of the arena size. Path texture analysis differs from fractal dimension analysis in that it does not assume self-similarity across scales. Path texture was found to discriminate inbred strains with relatively high broad-sense heritability (43%-71%) and high replicability across laboratories. Even genotypes that had similar path curvatures in some scales usually differed in other scales, and self-similarity across scales was not displayed by all genotypes. Amphetamine decreased the path curvature of C57BL/6 mice in small and medium scales, while having no effect on DBA/2J mice. Diazepam dose-dependently decreased the curvature of C57BL/6 mice across all scales, while 2 anxiogenic drugs, FG-7142 and pentylenetetrazole, increased it. Path texture thus has high potential for behavioral phenotyping and the study of drug effects in the mouse.

Rats and mice share common ethologically relevant parameters of exploratory behavior.

Detailed studies of rat exploratory behavior reveal that it consists of typical behavior patterns having a distinct structure. Recently we have developed interactive software that uses as input the automatically digitized time-series of the animal's location for the visualization, analysis, capturing and quantification of these patterns. We use this software here for the study of BALB/cJtau mouse behavior. The results suggest that a considerable number of rat patterns are also present in the mouse. These ethologically-relevant patterns have a significant potential as a phenotyping tool.

Controlling the false discovery rate in behavior genetics research.

The screening of many endpoints when comparing groups from different strains, searching for some statistically significant difference, raises the multiple comparisons problem in its most severe form. Using the 0.05 level to decide which of the many endpoints' differences are statistically significant, the probability of finding a difference to be significant even though it is not real increases far beyond 0.05. The traditional approach to this problem has been to control the probability of making even one such error--the Bonferroni procedure being the most familiar procedure achieving such control. However, the incurred loss of power stemming from such control led many practitioners to neglect multiplicity control altogether. The False Discovery Rate (FDR), suggested by Benjamini and Hochberg [J Royal Stat Soc Ser B 57 (1995) 289], is a new, different, and compromising point of view regarding the error in multiple comparisons. The FDR is the expected proportion of false discoveries among the discoveries, and controlling the FDR goes a long way towards controlling the increased error from multiplicity while losing less in the ability to discover real differences. In this paper we demonstrate the problem in two studies: the study of exploratory behavior [Behav Brain Res (2001)], and the study of the interaction of strain differences with laboratory environment [Science 284 (1999) 1670]. We explain the FDR criterion, and present two simple procedures that control the FDR. We demonstrate their increased power when used in the above two studies.

Natural segmentation of the locomotor behavior of drug-induced rats in a photobeam cage.

Recently, Drai et al. (J Neurosci Methods 96 (2000) 119) have introduced an algorithm that segments rodent locomotor behavior into natural units of 'staying in place' (lingering) behavior versus going between places (progression segments). This categorization, based on the maximum speed attained within the segment, was shown to be intrinsic to the data, using the statistical method of Gaussian Mixture Model. These results were obtained in normal rats and mice using very large (650 or 320 cm) circular arenas and a video tracking system. In the present study, we reproduce these results with amphetamine, phencyclidine and saline injected rats, using data measured by a standard photobeam tracking system in square 45 cm cages. An intrinsic distinction between two or three 'gears' could be shown in all animals. The spatial distribution of these gears indicates that, as in the large arena behavior, they correspond to the difference between 'staying in place' behavior and 'going between places'. The robustness of this segmentation over arena size, different measurement system and dose of two psychostimulant drugs indicates that this is an intrinsic, natural segmentation of rodent locomotor behavior. Analysis of photobeam data that is based on this segmentation has thus a potential use in psychopharmacology research.

A traveling wave of lateral movement coordinates both turning and forward walking in the ferret.

Relative phase was recently suggested as a key variable for the dynamical modeling of coordination in both quadruped locomotion and undulation swimming in fish. Relative phase analysis has not yet been applied, however, to the behavior of intact, freely moving animals, but only to simplified situations involving restrained animals and humans. In order to investigate relative phase under free movement conditions, we filmed free locomotion of ferrets (Mustella putorius) from below (through a glass floor) and measured the lateral bending along the head, torso, and tail, and the location of the four paws. We introduced an algorithm which extracts the phase (and thus also the relative phase) even when the movements were neither periodic nor symmetric. Our results show that relative phases between segments have preferred values, which are relatively independent of the amplitude, duration, and asymmetry of the movement. In particular, both walking and turning can be explained as modulations of a single pattern: a cephalo-caudal, traveling wave of lateral movement with a wavelength of approximately one length of the body. The relative phase between movements of adjacent segments is similar when the body is in S shape (i.e., when walking forward), or C shape (i.e., when turning). The movements of the paws in the horizontal plane can also be considered as part of this traveling wave. Our findings suggest that the concept of traveling waves of lateral bending, as found in the locomotion of undulating fish, can be generalized in two ways: (i) by considering the axis around which the movement is centered, it applies not only to forward locomotion, but also to turning: (ii) by incorporating the position of the paws, it applies also to the movement of quadrupeds. Our findings suggest that the relative phase, once it is generalized to asymmetric and quasi-periodic movement, is suitable for modeling coordination patterns under free movement conditions.

Coordination of side-to-side head movements and walking in amphetamine-treated rats: a stereotyped motor pattern as a stable equilibrium in a dynamical system.

Rats injected with 5.0 mg/kg (+)-amphetamine perform, at one stage of the drug's influence, rhythmic side-to-side head movements while walking. This makes them an interesting preparation for investigating how stereotyped motor patterns emerge from the coordination of periodic movements. We report here such a pattern we have isolated: the left foreleg and the right hindleg land on the ground as the head reaches the peak of its movement to the right, and vice versa (contra-lateral pattern). We show that this pattern can be explained as a stable equilibrium in a simple, nonlinear dynamical model, similar to models developed for tapping with both hands in human subjects. The model also accounts for sequences of behavior that are not in the contra-lateral pattern, explaining them as a flow of the system back towards the stable equilibrium after a disturbance. Motor patterns that constitute the building blocks of unconstrained behavior are often defined as fixed phase relations between movements of the parts of the body. This study applies the paradigm of Dynamic Pattern Generation to free (unconstrained) behavior: motor patterns are defined as stable equilibria in dynamical systems, assembled by mutual influence of concurrent movements. Our findings suggest that this definition is more powerful for the description of free behavior. The amphetamine-treated rat is a useful preparation for investigating this notion in an unconstrained animal whose behavior is still not as complex and variable as that of the normal animal.