Short- and long-term behavioral analysis of social interaction, ultrasonic vocalizations and social motivation in a chronic phencyclidine model.

Phencyclidine (PCP) has been suggested to induce symptoms of schizophrenia. However, animal models using PCP administration have produced ambiguous results thus far. It seems that acute effects are similar to symptoms of schizophrenia, however, it is not clear if PCP can induce permanent behavioral changes that reflect schizophrenic-like symptoms. Therefore, we assessed the ability of chronic PCP administration (3mg/kg, 14 days) to induce short or long lasting behavioral changes in rats. Social behavior, including ultrasonic vocalizations and motivation for social contact were investigated at different time points, up to 29-36 days, after cessation of PCP treatment. During a social separation test, performed at 5 and 36 days, PCP treated rats spent less time near the divider that separates them from their familiar cage mate compared with saline (SAL) treated rats. Further, at short term, PCP was able to induce a decrease in social behavior. In contrast, at long-term, PCP treated animals spent more time in contact when exposed to an unfamiliar partner as compared to SAL treated rats. But, this difference was not observed when exposed to a familiar partner. We did not find any difference in ultrasonic vocalizations at all time points. The results of our study indicate that PCP is unable to induce overt long term deficits in social interaction behavior. Rather, it seems that PCP diminishes motivation for social contact. The long-term consequences of chronic PCP administration on social behavior in rodent models remain complex, and future studies addressing this are still needed.

Novel approach to automatically classify rat social behavior using a video tracking system.

BACKGROUND: In the past, studies in behavioral neuroscience and drug development have relied on simple and quick readout parameters of animal behavior to assess treatment efficacy or to understand underlying brain mechanisms. The predominant use of classical behavioral tests has been repeatedly criticized during the last decades because of their poor reproducibility, poor translational value and the limited explanatory power in functional terms. NEW METHOD: We present a new method to monitor social behavior of rats using automated video tracking. The velocity of moving and the distance between two rats were plotted in frequency distributions. In addition, behavior was manually annotated and related to the automatically obtained parameters for a validated interpretation. RESULTS: Inter-individual distance in combination with velocity of movement provided specific behavioral classes, such as moving with high velocity when "in contact" or "in proximity". Human observations showed that these classes coincide with following (chasing) behavior. In addition, when animals are "in contact", but at low velocity, behaviors such as allogrooming and social investigation were observed. Also, low dose treatment with morphine and short isolation increased the time animals spent in contact or in proximity at high velocity. COMPARISON WITH EXISTING METHODS: Current methods that involve the investigation of social rat behavior are mostly limited to short and relatively simple manual observations. CONCLUSION: A new and automated method for analyzing social behavior in a social interaction test is presented here and shows to be sensitive to drug treatment and housing conditions known to influence social behavior in rats.

Conclusions on motor control depend on the type of model used to represent the periphery.

Within the field of motor control, there is no consensus on which kinematic and kinetic aspects of movements are planned or controlled. Perturbing goal-directed movements is a frequently used tool to answer this question. To be able to draw conclusions about motor control from kinematic responses to perturbations, a model of the periphery (i.e., the skeleton, muscle-tendon complexes, and spinal reflex circuitry) is required. The purpose of the present study was to determine to what extent such conclusions depend on the level of simplification with which the dynamical properties of the periphery are modeled. For this purpose, we simulated fast goal-directed single-joint movement with four existing types of models. We tested how three types of perturbations affected movement trajectory if motor commands remained unchanged. We found that the four types of models of the periphery showed different robustness to the perturbations, leading to different predictions on how accurate motor commands need to be, i.e., how accurate the knowledge of external conditions needs to be. This means that when interpreting kinematic responses obtained in perturbation experiments the level of error correction attributed to adaptation of motor commands depends on the type of model used to describe the periphery.

Do we use a priori knowledge of gravity when making elbow rotations?

In this study, we aim to investigate whether motor commands, emanating from movement planning, are customized to movement orientation relative to gravity from the first trial on. Participants made fast point-to-point elbow flexions and extensions in the transverse plane. We compared movements that had been practiced in reclined orientation either against or with gravity with the same movement relative to the body axis made in the upright orientation (neutral compared to gravity). For each movement type, five rotations from reclined to upright orientation were made. For each rotation, we analyzed the first trial in upright orientation and the directly preceding trial in reclined orientation. Additionally, we analyzed the last five trials of a 30-trial block in upright position and compared these trials with the first trials in upright orientation. Although participants moved fast, gravitational torques were substantial. The change in body orientation affected movement planning: we found a decrease in peak angular velocity and a decrease in amplitude for the first trials made in the upright orientation, regardless of whether the previous movements in reclined orientation were made against or with gravity. We found that these decreases disappeared after participants familiarized themselves with moving in upright position in a 30-trial block. These results indicate that participants used a general strategy, corresponding to the strategy observed in situations with unreliable or limited information on external conditions. From this, we conclude that during movement planning, a priori knowledge of gravity was not used to specifically customize motor commands for the neutral gravity condition.

Motor commands for fast point-to-point arm movements are customized for small changes in inertial load.

For repeated point-to-point arm movements it is often assumed that motor commands are customized in a trial-to-trial manner, based on previous endpoint error. To test this assumption, we perturbed movement execution without affecting the endpoint error by using a modest manipulation of inertia. Participants made point-to-point elbow flexion and extension movements in the horizontal plane, under the instruction to move as fast as possible from one target area to another. In selected trials the moment of inertia of the lower arm was increased or decreased by 25%. First, we found that an unexpected increase or decrease of inertia did not affect the open loop controlled part of the movement path (and thus endpoint error was not affected). Second, we found that when the increased or decreased inertia was presented repeatedly, after 5-11 trials motor commands were customized: the first 100ms of agonistic muscle activity in the smoothed and rectified electromyographic signal of agonistic muscles was higher for the high inertia compared to the low inertia. We conclude that endpoint error is not the only parameter that is used to evaluate if motor commands lead to movements as planned.

Isometric torque-angle relationships of the elbow flexors and extensors in the transverse plane.

Maximal voluntary isometric torque-angle relationships of elbow extensors and flexors in the transverse plane (humerus elevation angle of 90 degrees ) were measured at two different horizontal adduction angles of the humerus compared to thorax: 20 degrees and 45 degrees . For both elbow flexors and extensors, the torque-angle relationship was insensitive to this 25 degrees horizontal adduction of the humerus. The peak in torque-angle relationship of elbow extensors was found at 55 degrees (0 degrees is full extension). This is closer to full elbow extension than reported by researchers who investigated this relationship in the sagittal plane. Using actual elbow angles during contraction, as we did in this study, instead of angles set by the dynamometer, as others have done, can partly explain this difference. We also measured electromyographic activity of the biceps and triceps muscles with pairs of surface electrodes and found that electromyographic activity level of the agonistic muscles was correlated to measured net torque (elbow flexion torque: Pearson's r=0.21 and extension torque: Pearson's r=0.53). We conclude that the isometric torque-angle relationship of the elbow extensors found in this study provides a good representation of the force-length relationship and the moment arm-angle relationship of the elbow extensors, but angle dependency of neural input gives an overestimation of the steepness.

The dynamics of postural sway cannot be captured using a one-segment inverted pendulum model: a PCA on segment rotations during unperturbed stance.

Research on unperturbed stance is largely based on a one-segment inverted pendulum model. Recently, an increasing number of studies report a contribution of other major joints to postural control. Therefore this study evaluates whether the conclusions originating from the research based on a one-segment model adequately capture postural sway during unperturbed stance. High-pass filtered kinematic data (cutoff frequency 1/30 Hz) obtained over 3 min of unperturbed stance were analyzed in different ways. Variance of joint angles was analyzed. Principal-component analysis (PCA) was performed on the variance of lower leg, upper leg, and head-arms-trunk (HAT) angles, as well as on lower leg and COM angle (the orientation of the line from ankle joint to center of mass). It was found that the variance in knee and hip joint angles did not differ from the variance found in the ankle angle. The first PCA component indicated that, generally, the upper leg and HAT segments move in the same direction as the lower leg with a somewhat larger amplitude. The first PCA component relating ankle angle variance and COM angle variance indicated that the ankle joint angle displacement gives a good estimate of the COM angle displacement. The second PCA component on the segment angles partly explains the apparent discrepancy between these findings because this component points to a countermovement of the HAT relative to the ankle joint angle. It is concluded that postural control during unperturbed stance should be analyzed in terms of a multiple inverted pendulum model.