Integrated digital image and accelerometer measurements of rat locomotor and vibratory behaviour

This study developed a combined IC-type accelerometer and video camera system to simultaneously measure vibration and locomotion activities in rats. A personal computer, adopted as an image frame grabber, was combined with a digital image processing algorithm to measure the precise location of an animal in an experimental cage. An accelerometer-based vibration subsystem, based on an 89C51 single-chip microprocessor, was designed. The acceleration sensor module was attached directly to the shaved back of the rat's body to directly measure the animal's vibration. This module can detect a wide range of vibrations from movements of the entire body to micro-tremors. Along with hardware, this study also proposes novel software for video enhancement and data analysis to calculate the behaviour parameters from recorded movements. In normal mode, three vibration activities (locomotor activity, tremor and twitch) are auto-analyzed every 10 min. The results are saved, and various display, statistical and data organization options are available. The primary merits of this system are the ability to simultaneously record locomotion and vibrational data, the rapid set-up and operation, the low cost, the reduced illumination requirements, the reduction of environmental noise and the high precision. The proposed method will be of interest to researchers in various behavioural, biological and medical fields.     

Hypothalamic substrates for brain stimulation-induced patterns of locomotion and escape jumps in the rat

The hypothalamic response area for electrically induced locomotion was determined using moveable electrodes and discriminant analysis as an appropriate statistical technique. At 241 out of 641 stimulated sites locomotion was induced. The distribution of locomotion sites is relatively diffuse. Discriminant analysis of both positive and negative electrode localizations yields areas with high, intermediate or low probability of inducing the response. The response is considered to be mediated by fibres of the subpallido-pedunculopontine system, which includes the mesencephalic locomotor region. Different categories of exploratory and flight-directed locomotion were distinguished, and response areas for both categories were determined. In addition the response area for escape jumps was delimited. Exploratory locomotion is mainly induced from the lateral hypothalamus, while flight-directed locomotion and escape jumps are evoked from the medial hypothalamus. The response area for exploratory locomotion reflects the lateral hypothalamic distribution of the subpallidal projection to the mesencephalic locomotor region. A diffuse substrate for flight behavior seems to occupy almost the entire medial hypothalamus. It is concluded that a locomotor subroutine subserving different behavioural mechanisms can be activated at many hypothalamic sites.     

CatWalk gait analysis in assessment of functional recovery after sciatic nerve injury

Following peripheral nerve injury repair, improved behavioural outcome may be the most important evidence of functionality of axon regeneration after any repair strategy. A range of behavioural testing paradigms have been developed for peripheral nerve injury research. Complete injury of the adult rat sciatic nerve is frequently used in combination with walking track analysis. Despite its wide-spread use, these walking track analyses are unsuitable for the simultaneous assessment of both dynamic and static gait parameters. Conversely, a novel automated gait analysis system, i.e. CatWalk can simultaneously measure dynamic as well as static gait parameters and, importantly, it's easy to control for the speed of locomotion which can strongly affect gait parameters. In a previous study, CatWalk was already successfully used to examine deficits in both dynamic and static gait parameters using the sciatic nerve lesion model with a 1cm gap characterized by absence of recovery [Deumens R, Jaken RJ, Marcus MA, Joosten EA. The CatWalk gait analysis in assessment of both dynamic and static gait changes after adult rat sciatic nerve resection. J Neurosci Methods 2007;164:120-30]. Using the sciatic nerve crush injury model (validated with the static sciatic index) and a follow-up period of 12 weeks, we now show that CatWalk can also measure behavioural recovery. In particular dynamic gait parameters, coordination measures, and the intensity of paw prints are of interest in detecting recovery as far as these parameters completely return to pre-operative values after crush injury. We conclude that CatWalk can be used as a complementary approach to other behavioural testing paradigms to assess clinically relevant behavioural benefits, with a main advantage that CatWalk demonstrates both static and dynamic gait parameters at the same time.     

A combined system for measuring animal motion activities

In this study, we have developed a combined animal motion activity measurement system that combines an infrared light matrix subsystem with an ultrasonic phase shift subsystem for animal activity measurement. Accordingly, in conjunction with an IBM PC/AT compatible personal computer, the combined system has the advantages of both infrared and ultrasonic subsystems. That is, it can at once measure and directly analyze detailed changes in animal activity ranging from locomotion to tremor. The main advantages of this combined system are that it features real time data acquisition with the option of animated real time or recorded display/playback of the animal's motion. Additionally, under the multi-task operating condition of IBM PC, it can acquire and process behavior using both IR and ultrasound systems simultaneously. Traditional systems have had to make separate runs for gross and fine movement recording. This combined system can be profitably employed for normative behavioral activity studies and for neurological and pharmacological research.     

Is the cuneiform nucleus a critical component of the mesencephalic locomotor region? An examination of the effects of excitotoxic lesions of the cuneiform nucleus on spontaneous and nucleus accumbens induced locomotion

The cuneiform nucleus and the pedunculopontine tegmental nucleus have both been suggested as possible sites for the mesencephalic locomotor region (MLR), an area from which controlled stepping on a treadmill can be elicited following electrical or chemical stimulation in a decerebrate animal. It has been shown that excitotoxic lesions of the pedunculopontine tegmental nucleus impair neither spontaneous locomotion nor locomotion induced by stimulation of the nucleus accumbens. Excitotoxic lesions of the cuneiform nucleus have not previously been investigated. Rats received either bilateral ibotenate or sham lesions of the cuneiform nucleus combined with bilateral implantation of guide cannulae aimed at the nucleus accumbens. On recovery from surgery spontaneous locomotion was tested, followed by accumbens-stimulated locomotion. For nucleus accumbens stimulation, each rat received bilateral microinjection of each of three doses of d-amphetamine (10.0, 20.0 and 30.0 μg) and a vehicle only injection. Locomotor activity was recorded following the injection. In comparison to the sham-lesioned group, the ibotenate-lesioned group showed no differences in either spontaneous or amphetamine-induced locomotor activity. These results suggest that, like the pedunculopontine tegmental nucleus, the cuneiform nucleus is not involved in the direct mediation of spontaneous or accumbens-induced locomotion, and thus is very unlikely to be the anatomical substrate of the MLR. The role of the cuneiform nucleus in other types of behavioural control is discussed.     

Development of an animal model of fluoxetine akathisia

1. 1. Akathisia describes the pattern of intense inner restlessness often associated with neuroleptic and antidepressant treatment.

2. 2. The authors postulated that drug-induced akathisia would be characterized by more position changes and less time spent immobile, in the absence of significant increase in ambulation. In contrast, a psychomotor stimulant would produce both activation and ambulation.

3. 3. Procedures and instruments were developed to test this hypothesis. Adult rats were habituated for 72 hours to the testing environment, and their precise pattern of movements was tracked and recorded (10 reading per second; resolution 0.04 mm) by an infrared motion analysis system. Activity was recorded for a 90 min period after a single injection of sub-stereotypic doses of d-amphetamine (0, 0.3, 1.0 mg/kg) or racemic fluoxetine (0, 3.0, 10.0, 20.0, or 30.0 mg/kg, s.c.).

4. 4. Amphetamine produced both activation and ambulation. Activation was indicated by a decrease in time spent immobile, and an increase in the temporal scaling exponent, which reflects the degree the animal is “acting” in its environment, and the number of position changes. Enhanced locomotion was inferred from marked increases in both the total distance traversed and the ratio of forward movements-to-reversals and a decrease in the spatial scaling exponent, indicative of a less complex and more linear movement pattern.

5. 5. Fluoxetine caused animals to spend more time active, but exerted little effect on locomotion. Activation was indicated by a decrease in time spent immobile and an increase in the temporal scaling exponent and number of position changes. Fluoxetine failed to significantly effect either the ratio of forward movements-to-reversals or the spatial scaling exponent.

6. 6. These findings provide an operational definition and methodology that can be used to differentiate between psychostimulant effects and akathisic effects. This approach may have utility for screening drugs for akathisic potential, for exploring underlying mechanisms, and for developing novel treatments.

     

Impact of high and low anxiety on cognitive performance in a modified hole board test in C57BL/6 and DBA/2 mice

We investigated the interaction between behavioural dimensions and cognitive performance in the inbred mouse strains C57BL/6 and DBA/2, which have previously been found to differ in cognitive performance and emotionality. Because it has never been evaluated whether cognitive performance and emotional behaviour are interrelated in these strains, we analysed various behavioural dimensions and cognitive functions in parallel using the modified hole board test. We could show that naive BL6 and DBA mice distinctly differed in terms of anxiety-related behaviour. Principal component analysis on the phenotyping data showed that anxiety-related behaviour was described by identical parameters and was not correlated to locomotion in the two strains. During cognitive testing, DBA mice habituated faster and performed better than BL6 mice. Principal component analysis indicated a close correlation between anxiety-related behaviour and cognitive performance in DBA mice, being associated with a highly successful cognitive performance. In BL6 mice, cognition was correlated to general exploration. This correlation turned out to be less successful in performing the modified hole board test. Our findings support the idea that high anxiety may interact with specific cognitive processing, thus offering a promising animal model for future preclinical research on the interaction of anxiety and cognition.     

Tuning the network: modulation of neuronal microcircuits in the spinal cord and hippocampus

Adaptation of an organism to its changing environment ultimately depends on the modification of neuronal activity. The dynamic interaction between cellular components within neuronal networks relies on fast synaptic interaction via ionotropic receptors. However, neuronal networks are also subject to modulation mediated by various metabotropic G-protein-coupled receptors that modify synaptic and neuronal function. Modulation increases the functional complexity of a network, because the same cellular components can produce different outputs depending on the behavioural state of the animal. This review, which is part of the TINS Microcircuits Special Feature, provides an overview of neuromodulation in two neuronal circuits that both produce oscillatory activity but differ fundamentally in function. Hippocampal circuits are compared with the spinal networks generating locomotion, with a view to exploring common principles of neuromodulatory activity.     

Consequences of repeated early isolation in domestic piglets (Sus scrofa) on their behavioural, neuroendocrine, and immunological responses

Stress in the form of intermittent maternal deprivation and social isolation during early postnatal life in rats and monkeys produces persistent changes in physiology and behaviour. In farm animals physiological consequences of disrupting mother-infant interactions with respect to health and animal welfare are relatively unknown. Therefore, the aim of the present study was to investigate the behavioural, neuroendocrine and immunological consequences of a 2 h daily social isolation from day 3 to day 11 of age in domestic piglets as well as potential long-term effects on the brain-endocrine-immune regulation. Repeated social isolation resulted in significantly decreased open-field activity (locomotion, vocalization) during the isolation period, increased basal cortisol concentrations and decreased lymphocyte proliferation in response to concanavalin A and pokeweed mitogen one day after the isolation. There was also a significant increase of interleukin-1beta (IL-1beta) concentration in hippocampus in isolated piglets compared to controls at this time. Six weeks after isolation significant enhanced basal ACTH concentrations as well as higher IL-1beta content and glucocorticoid receptor (GR) binding in hippocampus were found. These endocrine and immune responses were associated with decreased CRH levels in the hypothalamus and increased CRH content in the amygdala. The present data indicate that early social isolation in pigs may cause changes in behavioural, neuroendocrine, and immune regulation and produce long-term effects not only on the activity of the hypothalamic-pituitary-adrenal (HPA) system, but also on the immune-brain circuitry with possible negative consequences in health and welfare of commercial pigs. Using the pig as a suitable animal model, the finding of this study may also have some implications for the etiology of anxiety and depression in humans.     

Alteration and recovery of appetitive behaviour following nerve section in the starfish Asterias rubens

The starfish Asterias rubens is an invertebrate deuterostome whose nervous system shows remarkable regenerative properties. To understand when full functionality of a damaged part of the nervous system recovers, and to follow nerve regeneration in detail, we carried out behavioural experiments with 29 starfishes that had the nerve in one of the arms sectioned in a mid-arm position. Loss and recovery of normal behaviour was followed by video analysis of animal performance in an appetitive behavioural test. When compared to 13 control (unoperated) animals, the appetitive response of freshly sectioned animals is normal initially, progressively deteriorates up to 40 days after the lesion, and then gradually improves until 60 days, when recovery is complete. This is true only when one of the leading arms in the appetitive test is a sectioned arm; turning the starfish so that both the leading arms facing the prey are unlesioned, results in normal behaviour even at 40 days after the cut. Thus, regeneration is a multi-step process whose time course coincides with anatomical regeneration. At intermediate times the animals have coordination problems in an appetitive behaviour test and these give some insights into how arms may inter-communicate to organize concerted movements.     

Behaviourally dependent modulation of lateral geniculate unit activity in the freely moving cat

In 120 neurons of the cat's dorsal lateral geniculate body (dLGB), spontaneous and light-evoked activity was analysed in order to obtain further information on firing characteristics during different behavioural states (quietly sitting, locomotion). Experiments were carried out in freely moving cats, using wireless methods for simultaneous registration of single unit activity and locomotion. During locomotion, an enhancement of neuronal single and pool activity was observed. During locomotor activity, flash-evoked responses were modulated, an increase of response amplitude and a decrease of peak latency in the peristimulus time histogram occurred. The results demonstrate a facilitatory influence on spontaneous and light-evoked activity of dLGB neurones during locomotion. They suggest a non-visual phasic modulation of retino-geniculo-cortical information transfer.     

Pharmacological validation of a novel home cage activity counter in mice

Many behavioural tests in rodents are based on the premise that basal locomotor activity of the animals is similar between the tested groups. The measurement of basal home cage activity is therefore an essential parameter, that should be included in all studies which employ tests of anxiety or cognition. Currently available systems for the assessment of home cage locomotion are often complex and expensive. Here we describe and validate a novel, simple and cost-efficient apparatus for the assessment of basic home cage locomotor activity in rodents. Circadian dark-light activity patterns can be reliably obtained with the home cage activity counter. Furthermore, changes in locomotion induced by novelty or pharmacological treatment were reliably and sensitively detected by the apparatus. Thus, the here presented home cage activity counter can be used for the measurement of basal home cage locomotor activity.     

Behavioural actions of prolactin locally applied into the hippocampus of adult female rats

Summary The probable behavioural effects of rat prolactin (rPRL) locally applied into the ventral hippocampus (HPC) were studied in cycling female rats. Three experiments were performed examining the behavioural responses of rats subjected to three different situations: (i) Exploratory activity in an enriched holeboard (ii) exploratory activity under conflicting situation and (iii) escape behaviours in a forced swimming test. Behavioural parameters studied were: underground and object-directed exploration and locomotion (Experiment 1); latency time and exploration behaviours (Experiment 2); swimming time and escape behaviours (Experiment 3). In Experiment 1 results showed that rPRL decreased the underground exploration and also locomotion but increased the object-directed exploration and had no effect on non-ambulatory activity. In Experiment 2 results showed that treatment of rPRL increased the latency time but did not modify the exploratory activity. In Experiment 3 results showed that rPRL augmented the swimming time and one of two parameters (frequency of immersions intents) of the escape behaviour. Results are interpreted as local actions of PRL on hippocampal neuron affecting expression of behaviours of rats depending on the stressful conditions of the environment.     

An animal model for the study of the genetic bases of behaviour in men: the multiple marker strains (MMS).

Animal models are often used for preclinical research on the neurobiology of psychiatric disorders. Whereas many are employed to screen new therapeutic agents, few of them are used to study the genetic bases of psychiatric diseases, probably because of the complex genetic determinism underlying quantitative behavioral traits such as mood, personality or intelligence. The present article presents a short review introducing an analysis model using mice: the marker strains model. Using this model it is possible both to display genetic determinism data and to locate some of the chromosomal fragments involved in the regulation of anxiogenic processes. At present it cannot accurately determine the position of one or more genes, but it does provide a valuable means of 'scanning' the genome for an approximation. Through genetic analysis, using the model, an attempt will be made to identify autosomal fragments which may be involved in two behavioural traits: anxiety and chemical-induced seizures. In this paper, after reviewing theoretical aspects of looking for genes involved in behaviour, we will successively introduce studies in genetic topics in psychiatric human studies as well as appropriated behavioural animal studies. Then we will present a genetic model in mice which allows us to locate chromosomal fragments associated with a behavioural trait: multiple marker strains.     

Cholinergically mediated reduction of locomotor activity from the basal forebrain of the rat

Carbachol when injected into the basal forebrain alters spontaneous motor behavior and usually decreases locomotion. However, the extent of the brain area producing this effect has not yet been determined. The goal of the present study was to use quantitative mapping of injection sites to further localize the effect of carbachol on spontaneous locomotion of rats. The distance travelled by an animal and the time spent moving were simultaneously measured before and after injection of carbachol or saline into 96 sites in the basal forebrain. Each site was injected with 1.0 microgram (5.47 nmol) of carbachol, a dose close to ED50, in a volume of 0.2 microliter. A decrease in spontaneous locomotion was obtained as a result of injections of carbachol into the preoptic and anterior hypothalamic areas, particularly into the medial preoptic nucleus and the latero-anterior hypothalamic nucleus. The area from which a consistent decrease in spontaneous locomotion was obtained was surrounded by an area producing an increase in locomotion with a narrow zone of overlap. This decrease in locomotion was dose dependent and reversed by atropine. The results indicate that both the decreasing and increasing effects of carbachol on locomotion are anatomically specific and that the decreasing effects can be elicited from a limited forebrain area. It is suggested that muscarinic cholinergic mechanisms in the basal forebrain may be involved in the pathogenesis of neural dysfunction associated with locomotor activity in man.     

A portable system for monitoring the behavioral activity of Drosophila

We describe a low-cost system for monitoring the behavioral activity of the fruit fly, Drosophila melanogaster. The system is readily adaptable to one or more cameras for simultaneous recordings of behavior from different angles and can be used for monitoring multiple individuals in a population at the same time. Signal processing allows discriminating between active and inactive periods during locomotion or flying, and quantification of subtler movements related to changes in position of the wings or legs. The recordings can be taken continuously over long periods of time and can thus provide information about the dynamics of a population. The system was used to monitor responses to caffeine, changes in temperature and g-force, and activity in a variable size population.     

Alpha-synuclein in the nucleus accumbens induces changes in cocaine behaviour in rats

The mesolimbic dopaminergic system is widely recognized to be critical to the neurobiology of cocaine reward and addiction. The neuronal protein, alpha-synuclein, is an important regulator in dopaminergic transmission. It interacts with the dopamine transporter, and regulates dopaminergic content, neurotransmission and synaptic strength of dopaminergic neurons. Alpha-synuclein levels are elevated in midbrain dopamine neurons of chronic cocaine abusers, and its expression is increased in psychostimulant-treated animals [M.S. Brenz-Verca et al. (2003) J. Neurosci., 18, 1923-1938]. This suggests a role for alpha-synuclein in psychostimulant-induced behavioural effects. To investigate this hypothesis, we tested the effect of stimulation and silencing of alpha-synuclein expression in the nucleus accumbens (NAcc) on two cocaine-induced behavioural effects in the rat. For this purpose, animals were administered with lentiviruses driving alpha-synuclein overexpression under the control of a doxycycline regulatable promoter and/or with three lentiviruses expressing target-specific siRNAs, aimed at silencing alpha-synuclein mRNA expression. Animals were then tested for cocaine-induced locomotion (15 mg/kg i.p.) or cocaine-induced intravenous self-administration (SA; 0.7 mg/kg, 1 h/day). Overexpression of alpha-synuclein in the NAcc induced a 45% increase in locomotor activity and a 1.9-fold increase of cocaine SA, which could be abolished when the same animal was fed doxycycline. Furthermore, local inhibition of alpha-synuclein in the NAcc resulted in significant hypolocomotion activity and a decrease in SA. Our results demonstrate that alpha-synuclein is able to modulate cocaine-induced behavioural effects. This suggests that targeting alpha-synuclein function could provide new therapeutic strategies to treat cocaine abuse, for which there is no available treatment.     

Advanced paternal age is associated with alterations in discrete behavioural domains and cortical neuroanatomy of C57BL/6J mice

Advanced paternal age (APA) is associated with an increased risk of neurodevelopmental disorders such as autism and schizophrenia. A previous study in mice suggested that the offspring of aged sires have altered locomotion and avoidance learning. The aim of the current study was to conduct a comprehensive behavioural screen in adult offspring of mice of APA. We also examined brain morphology in neonate and adult mice. The adult offspring of 12‐ to18‐month‐old (APA) and 4‐month‐old (control) male C57BL/6J mice underwent a behavioural test battery comprising tests for locomotion, anxiety, exploration, social behaviour, learned helplessness and sensorimotor gating. The brains of these mice were collected at 3 months and imaged ex vivo using a 16.4T MRI scanner to assess gross neuroanatomy. Neuroanatomy was also examined at birth in a separate cohort of animals. Overall, the APA mouse model was associated with subtle behavioural changes and altered cortical morphology. The behavioural phenotype of female APA mice included increased anxiety‐related behaviour, increased exploration and decreased learned helplessness compared to control females. Male APA mice had thinner cortices at birth and increased cortical volume as adults. This animal model may assist in exploring the mechanism of action linking APA with disorders such as schizophrenia and autism.