Locomotor Activity & Exploration Guide

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1 Locomotor Activity & Exploration Guide Locomotor activity refers to the movement from one location to another. In rodents, one of the most important components of exploration, a prominent activity of the animal s repertoire of spontaneous activity, is locomotion. Moreover, locomotor activity and exploration are involved in many behavioral and physiological functions and are influenced by many external factors, such as environmental conditions (light, temperature, noise) and novelty, and internal factors, such as circadian rhythm, food- or drink-deprivation, prior handling by the researcher, age, gender, strain, and many other factors. Development of behavioral measurements of locomotor activity and exploration was in part relevant in various rodent models as an initial screen for pharmacological effects predictive of therapeutic drug efficacy in humans. Indeed, locomotor and exploration are mediated by neurotransmitters affected by many types of drugs, such as neuroleptic, benzodiazepines, opiates and psychostimulants, and consequently are changed in response to the administration of these drugs. Moreover, alterations of locomotor activity and exploration can have important consequences for paradigms that aim to study more specific processes, such as learning, memory, reward, anxiety and others. Thus, it is imperative to verify if a difference in drug, lesion, strain or genetic manipulation influences general motor activity. Furthermore, locomotor abnormalities are associated with several human disease models such as Parkinson s and Huntington s diseases and hyperactivity syndrome. Abnormalities in activity are therefore displayed by animal models. 10

2 Locomotor Activity & Exploration Guide Circadian Locomotor Activity Rodents typically display circadian rhythmic variations (defined as a 24-hour rhythm) in behavior and physiology. Circadian global activity is directly assessed in the animal home cage through long periods (>24 hours). The activity parameters (locomotion, exploration, stereotypies) are generally evaluated using automated procedures (ex: photocell beams, video tracking systems, or weight transducers). No need for habitation; not stressful, familiar environment for the subject Long-term observation of activity (circadian rhythm) Easy to perform tests No animal handling needed Open Field Test for Basal Global Activity Basal locomotor activity is generally assessed in a specific activity arena (can be an open field or other) for short or intermittent periods (<1 hour). Locomotion (horizontal activity), exploration (rearing and object sniffing) and stereotypies (movement without displacement) are then recorded manually or using various automated procedures (photocell beams, videotracking system, or weight transducers). Free exploration paradigm Widely used in literature Easy to use for inexperienced users Can be entirely automated Reasons for Not Choosing This Test Attention-Deficit Hyperactivity Disorder Requires non-stressful conditions (habituation and low lighting conditions) Parkinson s Disease Huntington s Disease Attention-Deficit Hyperactivity Disorder (ADHD) 11

3 Locomotor Activity & Exploration Guide Activity Wheel The Rodent Activity Wheel represents a very simple and clever way to register animal physical activity in its home cage environment. The use of this high throughput tool is particularly relevant for research involving circadian rhythms, phenotyping and drug testing. Typically, the time and distance run on a voluntary running wheel are monitored over several days or weeks to determine whether a particular substance or experimental manipulation has an effect on exercise behavior. Rodent voluntary exercise registering; allows animals to exercise when and at the intensity that they choose Availability of a running wheel may reduce the effects of chronic stress on depression-like signs in mice Less labor intensive than treadmill running as researchers need not to be present during wheel running Relatively inexpensive setup Ideal for high throughput experiments; many animals can be trained at the same time Reasons for Not Choosing This Test Intensity and duration of the exercise cannot be controlled Certain lines of transgenic mice may not engage in enough voluntary wheel running exercise to produce training adaptations Not suitable for studies that require precise timing to explore acute post exercise adaptations (intermittent running throughout the active cycle) Locomotor Response to Novelty Locomotor Response to Novelty is an index of animal exploration/anxiety that has been shown to represent a predictive factor for the addictive properties of a drug. In an animal model for vulnerability to drug abuse, animals that exhibit greater motor activity in a novel environment (high responders; HR) are found more sensitive to drugs of abuse and are more likely to self-administer these drugs compared to less reactive animals (low responders, LR). In the light of clinical evidence on comorbidity between drug abuse and mood disorders, this model is widely used to investigate whether individual differences in locomotor reactivity to novelty are related to anxiety and depression-like responsiveness in rodents. Explore novelty-seeking behaviors Free exploration paradigm Test maximizing avoidance/anxiety related behavior respect to approach/exploratory behavior Only one exposure (no habituation) and quickly performed Easy to run Sensitive for mice and rats Reasons for Not Choosing This Test Anxiogenic conditions (novel environment with no possibility of escape) Addiction Anxiety Disorders Neuromuscular Disease Parkinson s Disease Muscular Dystrophy 12

4 Locomotor Activity & Exploration Guide Emergence Test The Emergence Test is a free exploration paradigm designed to reduce anxiety by providing a safe enclosure within the open field in order to assess approach or exploratory behavior in rodents. Briefly, the open field contained a white plastic cylinder with an open end centrally located. The subjects are placed into the cylinder and tested for 10 to 15 minutes. The parameters commonly evaluated in this task are the latency of emergence from the cylinder, the total time spent inside the cylinder, the time spent exploring the cylinder and general locomotor activity. Free exploration paradigm in reduced anxiogenic environment Easy to run Novel Object Test The Novel Object Test is a free exploration paradigm that provides animals the opportunity to explore a novel object in a familiar environmental context. Briefly, an object is placed into the center of each open field and the behavior of the animal (time spent exploring the novel object and overall locomotor activity) is registered during a determined period of time. Free exploration paradigm in a familiar environment Test maximizing approach/exploratory behavior respect to avoidance/anxiety-related behavior Easy to run, even for inexperienced users Parkinson s Disease Parkinson s Disease 13

5 Locomotor Activity & Exploration Guide Hole Board Test The Hole Board Test is a specific test for evaluating exploration in rodents. In this test, the animal is placed on an arena with regularly arranged holes on the floor. Both frequency and duration of spontaneous elicited hole-poking exploratory behavior are then measured manually or using automated procedures (photocell beams, video tracking system) during a short period of time. Other associated behaviors can also be evaluated, such as grooming, rearing and locomotion. Allows differentiation between inquisitive and inspective exploration Very sensitive to drug effects Can be completely automated Easy to use, even for inexperienced users Treadmill The Treadmill Test in rodents is a useful tool with a great value in the study of functional capacity and is a validated standard model for investigations in the field of human metabolism. A subject is forced to walk/run on a treadmill (adjustable speed and inclination) during specific periods of time. This test allows the study of various physiological and behavioral functions such as long and short-term effort during exercise, locomotion, metabolic exchanges, cardiac function, motor coordination and fatigue. Adapted from a human test Allows the researcher to precisely control the level of exertion Easy to use, even for inexperienced users Sensitive for mice and rats Reasons for Not Choosing This Test Needs repetitive daily exposure during few weeks Requires constant vigilance by the researcher to make sure that the animals run for the entire exercise bout Use of aversive stimuli to encourage running Improvement of sportive human performances Oxidative Stress Diabetes Parkinsons s Disease Ischemia Ostopenia/Osteoporosis 14

6 ActiTrack Software for IR Actimeter Key Features software species is hardware specific Control up to 32 frames Provides spatial position, pattern of displacement and rearings User-adjustable thresholds for classifying activity into fast, slow and resting movements Allows track re-analysis with an unlimited number of user-defined zones Enables re-playing experiment using different threshold for movement speed definition Can be installed in as many computers as may be required for track analysis Parameters Measured Traveled distance (and % ) into user-defined zones Maximum, minimum and mean speed Time (and %) moving fast, slow and resting Permanence time (and %) into user-defined zones Number of entrances into user-defined zones Number and mean duration of rearings Number of clockwise and counter-clockwise turns Track history analysis Components Included Software CD with USB protection key Instruction manual Free software updates of the acquired system (excluding UPGRADES) Specifications Computer Requirements System Requirements Order # Model 2.2 GHz Processor or higher (Celeron processor excluded), 2 Gb of RAM Windows XP compatible operating system (SP2 or higher), Vista 32 Product BH ActiTrack Tracking Software for up to 32 IR Frames Citations Chetrit J et al. (2009) Involvement of Basal Ganglia Network in Motor Disabilities Induced by Typical Antipsychotics. PLoS One. 4(7):e6208. (Open-field with Actitrack, rat, France). Lamberty Y et al. (2009) Behavioural phenotyping reveals anxiety-like features of SV2A deficient mice. Behav. Brain Res. 198(2): (mouse, Belgium) Tsuchida R et al. (2009) An Antihyperkinetic Action by the Serotonin 1A Receptor Agonist Osemozotan Co-administered With Psychostimulants or the Non-stimulant Atomoxetine in Mice. J. Pharmacological Sci. 109(3): (locomotion, mouse, Japan) Goeldner C et al. (2008) Nociceptin Receptor Impairs Recognition Memory via Interaction with NMDA Receptor-Dependent Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Signaling in the Hippocampus. J Neurosci., 28(9): (object-recognition test, mouse, France) Rubio M (2008) CB1 receptor blockade reduces the anxiogenic-like response and ameliorates the neurochemical imbalances associated with alcohol withdrawal in rats. Neuropharmacology. 54(6): (rat, Spain, USA) Reiss D et al (2007) Effects of social crowding on emotionality and expression of hippocampal nociceptin/orphanin FQ system transcripts in mice. Behav. Brain Res. 184(2): (mouse, France) Sonnier L et al. (2007) Progressive loss of dopaminergic neurons in the ventral midbrain of adult mice heterozygote for Engrailed1. J Neurosci. 27(5): (mouse, France) Kucerova J et al. (2006) Gender differences in cannabinoid and ecstasy interacting effects in mice. Homeostasis in health and diseases. 2006(1-2): (mouse, Czech Republic) Menendez J et al. (2006) Suppression of Parkin enhances nigrostriatal and motor neuron lesion in mice over-expressing human-mutated tau protein. Human Molecular Genetics. 15(13): (mouse, Spain) Tanaka et al. (2006) Psychostimulant-Induced Attenuation of Hyperactivity and Prepulse Inhibition Deficits in Adcyap1-Deficient Mice. J. Neurosci. 26(19): (mouse, Japan) Locomotor Activity & Exploration I ActiTrack Software for IR Actimeter Harvard Apparatus phone toll free U.S fax Panlab Harvard Apparatus Spain International fax

7 IR Actimeter Locomotor Activity & Exploration I IR Actimeter ActiTrack Tracking Software Key Features Interchangeable frames can be used without distinction for rearing activity or poking modes Can be used without any computer (independent control units) Dedicated PC optional, not required Parameters Measured Fast/Slow activity; i.e. movements with displacement (control unit) Fast/Slow stereotypies; i.e. movements without displacement (control unit) Fast/Slow rearings (control unit) Fast/Slow nose-spoke (control unit) Analysis of animal tracking: distance covered, speed, rearings, permanence time in selected zones, etc. (ActiTrack) Intervals of inactivity (ActiTrack) Time in zone (ActiTrack) Distance travelled (ActiTrack) Rearing behavior events and duration (ActiTrack) Components Included IR unit and control unit with RS-232 communications port SeDaCom software Cables and connectors Instruction manual Set of spare fuses 2 year warranty on hardware Options ActiTrack software, see page 15 Arena dividers Hole poke board Transparent acrylic arena IR Actimeter The Panlab/Harvard Apparatus Infrared (IR) Actimeter allows the study of spontaneous locomotor activity, rearing and optional holeboard test parameters for exploration in rodents. A reliable system for easy and rapid drug screening and phenotype characterization in both day and night lighting conditions. The system is composed of a two dimensional (X and Y axes) square frame, a frame support and a control unit. Each frame counts with 16 x 16 infrared beams for optimal subject detection. The system is completely modular: each frame may be used for evaluation of general activity (one or more animals), locomotor, stereotypic movements, rearings or exploration (nose-spoke detection in the hole-board option). The infrared photocell system can be set with up to 15 levels of sensitivity in order to adapt the frames to the typology of the animal (rats, mice). It can also be set to ignore the beams that are obstructed by objects (e.g. the walls/corners of the home cage). The frames can be controlled by independent control units or directly through SeDaCom computer software, which allows easy exportation of data (through RS-232 serial port) in a format compatible with Excel. Optionally, the ActiTrack software option may be used to analyze animal trajectories (distance, speed, permanence time in selected zones) and then provide additional complementary data to those obtained using the control units. 16 Harvard Apparatus phone toll free U.S fax Panlab Harvard Apparatus Spain International fax

8 IR Actimeter (continued) Specifications System Dimensions: LE 8811 LE 8812 Number of InfraRed Beams Per Frame InfraRed Photocells Spacing: LE 8815 LE 8816 Material Composition Computer Requirements Maximum Number of Stations Power Requirements Certifications 450 (W) x 450 (D) x 200 (H) mm 220 (W) x 220 (D) x 200 (H) mm 32 (16 per axis) 25mm 13mm Aluminum, polypropylene PC (Windows 95, 98, ME, NT, 2000, XP & Vista 32) (if SeDaCom is to be Used) 32 InfraRed Frames per computer (either SeDaCom or ActiTrack) 110/220 V, 50/60 Hz CE compliant Citations Canini F et al. (2009) Metyrapone decreases locomotion acutely. Neurosci. Letters. 457(1): (locomotion, rat, France) Chetrit J et al. (2009) Involvement of Basal Ganglia Network in Motor Disabilities Induced by Typical Antipsychotics. PLoS One. 4(7):e6208. (Open-field with Actitrack, rat, France). Lamberty Y et al. (2009) Behavioural phenotyping reveals anxiety-like features of SV2A deficient mice. Behav. Brain Res. 198(2): (mouse, Belgium) Lopez-Aumatell R et al. (2009) Unlearned anxiety predicts learned fear: A comparison among heterogeneous rats and the Roman rat Straits. Behavioural Brain Research, 202: (Spontaneous activity, rats, Spain, UK, Switzerland) Tsuchida R et al. (2009) An Antihyperkinetic Action by the Serotonin 1A Receptor Agonist Osemozotan Co-administered With Psychostimulants or the Non-stimulant Atomoxetine in Mice. J. Pharmacological Sci. 109(3): (locomotion, mouse, Japan) Goeldner C et al. (2008) Nociceptin Receptor Impairs Recognition Memory via Interaction with NMDA Receptor-Dependent Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Signaling in the Hippocampus. J Neurosci., 28(9): (object-recognition test, mouse, France) Lalonde R and Strazielle (2008) Exploratory activity and motor coordination in old versus middleaged C57BL/6J mice. Arch. Gerontol. Geriat. Article in Press (Locomotor activity, mouse, Canada) Order # Model Product BH LE8811 Double IR System, Rats & Mice (Includes LE8825, LE8817, 2 Units LE8815 and SeDaCom) BH LE8810 Double IR Activity System, Mice (Includes LE8825, LE8818, 2 Units LE8816 and SeDaCom) BH LE8812 Single IR Activity System, Rats (Includes LE8825, LE8817, LE8815 and SeDaCom Software) BH LE8809 Single IR Activity System, Mice (Includes LE8825, LE8818, LE8816 and SeDaCom Software) BH LE8821 Arena Divider for LE 8815 (Allows Monitoring of 2 Animals at Once) BH LE8823 Arena Divider for LE 8816 (Allows Monitoring of 2 Animals at Once) OPTIONS BH ACTITRACK Enhanced Tracking Software for up to 32 Frames BH LE8815 IR FRAME, 450 x 450 mm, 16 x 16 IR Beams BH LE8816 IR FRAME, 250 x 250 mm, 16 x 16 IR Beams BH LE8814 Transparent Arena 440 x 440 mm (Open Field) BH LE8813 Transparent Arena 210 x 210 mm (Open Field) BH LE8817 Support for LE 8815 Frames BH LE8818 Support for LE 8816 Frames BH LE8820 Hole Poke Base for LE 8815 Frame BH LE8825 Data Logger (up to 200 Hours Memory) and PC Interface Lalonde R and Strazielle (2008) Relations between open-field, elevated plus-maze, and emergence tests as displayed by C57/BL6J and BALB/c mice. J: Neurosci. Meth. 171(1):48-52 (Locomotor activity, mouse, Canada) Lalonde R et al. (2008) Effects of a B-vitamin-deficient diet on exploratory activity, motor coordination, and spatial learning in young adult Balb/c mice. Brain Res. 1188: (open field, mouse, Canada) Goeldner C et al. (2008) Nociceptin Receptor Impairs Recognition Memory via Interaction with NMDA Receptor-Dependent Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Signaling in the Hippocampus. J Neurosci., 28(9): (object-recognition test, mouse, France) Rubio M (2008) CB1 receptor blockade reduces the anxiogenic-like response and ameliorates the neurochemical imbalances associated with alcohol withdrawal in rats. Neuropharmacology. 54(6): (rat, Spain, USA) Belujon P et al (2007) Noradrenergic Modulation of Subthalamic Nucleus Activity: Behavioral and Electrophysiological Evidence in Intact and 6-Hydroxydopamine-Lesioned Rats. J Neurosci. 27(36): (Parkison rats, France) Sonnier L et al. (2007) Progressive loss of dopaminergic neurons in the ventral midbrain of adult mice heterozygote for Engrailed1. J Neurosci. 27(5): (mouse, France) Locomotor Activity & Exploration I IR Actimeter Harvard Apparatus phone toll free U.S fax Panlab Harvard Apparatus Spain International fax

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