A Fully Automated Rodent Conditioning Protocol for Sensorimotor Integration and Cognitive Control Experiments

Rodents have been traditionally used as a standard animal model in laboratory experiments involving a myriad of sensory, cognitive, and motor tasks. Higher cognitive functions that require precise control over sensorimotor responses such as decision-making and attentional modulation, however, are typically assessed in nonhuman primates. Despite the richness of primate behavior that allows multiple variants of these functions to be studied, the rodent model remains an attractive, cost-effective alternative to primate models. Furthermore, the ability to fully automate operant conditioning in rodents adds unique advantages over the labor intensive training of nonhuman primates while studying a broad range of these complex functions.Here, we introduce a protocol for operantly conditioning rats on performing working memory tasks. During critical epochs of the task, the protocol ensures that the animal''s overt movement is minimized by requiring the animal to ''fixate'' until a Go cue is delivered, akin to nonhuman primate experimental design. A simple two alternative forced choice task is implemented to demonstrate the performance. We discuss the application of this paradigm to other tasks.     

Task Design Influences Prosociality in Captive Chimpanzees (Pan troglodytes)

Chimpanzees confer benefits on group members, both in the wild and in captive populations. Experimental studies of how animals allocate resources can provide useful insights about the motivations underlying prosocial behavior, and understanding the relationship between task design and prosocial behavior provides an important foundation for future research exploring these animals'' social preferences. A number of studies have been designed to assess chimpanzees'' preferences for outcomes that benefit others (prosocial preferences), but these studies vary greatly in both the results obtained and the methods used, and in most cases employ procedures that reduce critical features of naturalistic social interactions, such as partner choice. The focus of the current study is on understanding the link between experimental methodology and prosocial behavior in captive chimpanzees, rather than on describing these animals'' social motivations themselves. We introduce a task design that avoids isolating subjects and allows them to freely decide whether to participate in the experiment. We explore key elements of the methods utilized in previous experiments in an effort to evaluate two possibilities that have been offered to explain why different experimental designs produce different results: (a) chimpanzees are less likely to deliver food to others when they obtain food for themselves, and (b) evidence of prosociality may be obscured by more “complex” experimental apparatuses (e.g., those including more components or alternative choices). Our results suggest that the complexity of laboratory tasks may generate observed variation in prosocial behavior in laboratory experiments, and highlights the need for more naturalistic research designs while also providing one example of such a paradigm.     

Automated Visual Cognitive Tasks for Recording Neural Activity Using a Floor Projection Maze

Neuropsychological tasks used in primates to investigate mechanisms of learning and memory are typically visually guided cognitive tasks. We have developed visual cognitive tasks for rats using the Floor Projection Maze^1,2 that are optimized for visual abilities of rats permitting stronger comparisons of experimental findings with other species.In order to investigate neural correlates of learning and memory, we have integrated electrophysiological recordings into fully automated cognitive tasks on the Floor Projection Maze^1,2. Behavioral software interfaced with an animal tracking system allows monitoring of the animal''s behavior with precise control of image presentation and reward contingencies for better trained animals. Integration with an in vivo electrophysiological recording system enables examination of behavioral correlates of neural activity at selected epochs of a given cognitive task.We describe protocols for a model system that combines automated visual presentation of information to rodents and intracranial reward with electrophysiological approaches. Our model system offers a sophisticated set of tools as a framework for other cognitive tasks to better isolate and identify specific mechanisms contributing to particular cognitive processes.     

Self-aggression in macaques: Five case studies

Spontaneous self-aggressive behaviors were observed in five adult male rhesus monkeys (Macaca mulatta) housed at a university facility. All were individually caged, were free of intercurrent disease, and were being utilized in ongoing research studies. The self-aggressive behaviors observed included self-biting, self-clasping, self-slapping, self-rubbing and threatening of body parts. In several cases, wounds were inflicted and medical treatment was required due to the severity of the lesions. A review of the animals' clinical histories revealed an increased level of self-aggressive behavior in four of five monkeys during such stressful or stimulating conditions as movement of the animal to a new cage, movement of animals out of the room or escape of other monkeys from their cages. The frequency with which these behaviors occurred was quantitated experimentally. The results revealed an increased level of self-aggressive behavior in two of these animals during the videotaped sessions in response to aggressive contacts with the investigator. In contrast, one monkey exhibited self-aggressive behavior both clinically and experimentally in the absence of environmental stimuli or human contact. Clinical management of self-aggressive monkeys included housing monkeys only with physically smaller primates, decreasing the level of environmental stimuli, and drug therapy. Haloperidol was used with success in one animal that exhibited severe self-aggressive behavior.     

Prospective Control in Catching: The Persistent Angle-of-Approach Effect in Lateral Interception

In lateral interception tasks balls converging onto the same interception location via different trajectories give rise to systematic differences in the kinematics of hand movement. While it is generally accepted that this angle-of-approach effect reflects the prospective (on-line) control of movement, controversy exists with respect to the information used to guide the hand to the future interception location. Based on the pattern of errors observed in a task requiring visual extrapolation of line segments to their intersection with a second line, angle-of-approach effects in lateral interception have been argued to result from perceptual biases in the detection of information about the ball''s future passing distance along the axis of hand movement. Here we demonstrate that this account does not hold under experimental scrutiny: The angle-of-approach effect still emerged when participants intercepted balls moving along trajectories characterized by a zero perceptual bias with respect to the ball''s future arrival position (Experiment 4). Designing and validating such bias-controlled trajectories were done using the line-intersection extrapolation task (Experiments 2 and 3). The experimental set-up used in the present series of experiments was first validated for the lateral interception and the line-intersection extrapolation tasks: In Experiment 1 we used rectilinear ball trajectories to replicate the angle-of-approach effect in lateral interception of virtual balls. Using line segments extracted from these rectilinear ball trajectories, in Experiment 2 we replicated the reported pattern of errors in the estimated locus of intersection with the axis of hand movement. We used these errors to develop a set of bias-free trajectories. Experiment 3 confirmed that the perceptual biases had been corrected for successfully. We discuss the implications on the information-based regulation of hand movement of our finding that the angle-of-approach effect in lateral interception cannot not explained by perceptual biases in information about the ball''s future passing distance.     

Correlating Behavioral Responses to fMRI Signals from Human Prefrontal Cortex: Examining Cognitive Processes Using Task Analysis

The aim of this methods paper is to describe how to implement a neuroimaging technique to examine complementary brain processes engaged by two similar tasks. Participants'' behavior during task performance in an fMRI scanner can then be correlated to the brain activity using the blood-oxygen-level-dependent signal. We measure behavior to be able to sort correct trials, where the subject performed the task correctly and then be able to examine the brain signals related to correct performance. Conversely, if subjects do not perform the task correctly, and these trials are included in the same analysis with the correct trials we would introduce trials that were not only for correct performance. Thus, in many cases these errors can be used themselves to then correlate brain activity to them. We describe two complementary tasks that are used in our lab to examine the brain during suppression of an automatic responses: the stroop¹ and anti-saccade tasks. The emotional stroop paradigm instructs participants to either report the superimposed emotional ''word'' across the affective faces or the facial ''expressions'' of the face stimuli^1,2. When the word and the facial expression refer to different emotions, a conflict between what must be said and what is automatically read occurs. The participant has to resolve the conflict between two simultaneously competing processes of word reading and facial expression. Our urge to read out a word leads to strong ''stimulus-response (SR)'' associations; hence inhibiting these strong SR''s is difficult and participants are prone to making errors. Overcoming this conflict and directing attention away from the face or the word requires the subject to inhibit bottom up processes which typically directs attention to the more salient stimulus. Similarly, in the anti-saccade task^3,4,5,6, where an instruction cue is used to direct only attention to a peripheral stimulus location but then the eye movement is made to the mirror opposite position. Yet again we measure behavior by recording the eye movements of participants which allows for the sorting of the behavioral responses into correct and error trials⁷ which then can be correlated to brain activity. Neuroimaging now allows researchers to measure different behaviors of correct and error trials that are indicative of different cognitive processes and pinpoint the different neural networks involved.     

Genetic Engineering and Other Factors That Might Affect Human-Animal Interactions in the Research Setting

Evidence exists, particularly in the welfare literature of nonhuman animals on the farm, that the interaction between nonhuman animals and the personnel who care for them can have a strong effect on the animals' behavior, productivity, and welfare. Among species commonly used for biomedical research, mice appear to be the least-preferred species in animal care facilities. A review of the literature and observations of animal care staff interacting with mice indicated that the following factors may influence this: their small size, their particular behavioral characteristics, and husbandry constraints (such as housing in ventilated racks). In addition, this study questioned whether animal care personnel have a different perception of genetically engineered animals and whether this, in turn, has an effect on their interactions with these animals. The ability to carefully observe an animal's behavior is key in carrying out an animal-wellness assessment and in minimizing pain and distress. Attention to human-animal interactions in the research setting represents an opportunity for refinement for large numbers of animals and potentially for reduction of animal use.     

On the social nature of eyes: The effect of social cues in interaction and individual choice tasks

In an experimental setting, we applied a dual strategy to better understand the effect of pictures of eyes on human behavior. First, we investigated whether the effect of eyes was limited to interaction tasks in which the subjects' decisions influenced the outcomes of other subjects. We expanded the range of tasks to include individual choice tasks in which the subjects' decisions only influenced their own outcomes. Second, we investigated whether pictures of eyes were one of many social cues or were unique in their effect. We compared the effect of pictures of eyes with the effect of a different condition in which we presented the subjects with pictures of other students (peers). Our results suggest that the effect of pictures of eyes is limited to interaction tasks and that eyes should be considered distinct from other social cues, such as reminders of peers. While pictures of eyes uniformly enhanced pro-social behavior in interaction tasks, this was not the case for reminders of peers. Furthermore, the reminders of peers led to more rational behavior in individual choice tasks, whereas the effect of pictures of eyes was limited to situations involving interaction. Combined, these findings are in line with the claim that the effect of pictures of eyes on behavior is caused by a social exchange heuristic that works to enhance mutual cooperative behavior.     

Fitts' law is not continuous in reciprocal aiming

It takes longer to accomplish difficult tasks than easy ones. In the context of motor behaviour, Fitts'' famous law states that the time needed to successfully execute an aiming movement increases linearly with task difficulty. While Fitts'' explicit formulation has met criticism, the relation between task difficulty and movement time is invariantly portrayed as continuous. Here, we demonstrate that Fitts'' law is discontinuous in reciprocal aiming owing to a transition in operative motor control mechanisms with increasing task difficulty. In particular, rhythmic movements are implemented in easy tasks and discrete movements in difficult ones. How movement time increases with task difficulty differs in both movement types. It appears, therefore, that the human nervous system abruptly engages a different control mechanism when task difficulty increases.     

Designating Seasonality Using Rate of Movement

ABSTRACT Traditionally, seasons for animals have been designated based on single external variables such as climate or plant phenology, rather than an animal's response to the dynamic environments within which it lives. By interpreting a rate of movement function of cumulative movement through time we established a method that distinguishes transitions between behaviors limited by winter habitat conditions from those present during summer. Identification of these time periods provides temporal definition to subsequent home-range analyses and use-availability comparisons. We used location data from 32 Global Positioning System-collared female moose (Alces alces) to demonstrate the method. We used model selection (Akaike's Information Criterion) to differentiate between candidate rate of movement response curves. Of 32 moose, 29 clearly conformed to an annual movement pattern described by a logistic curve, with increased rates of movement in summer compared to winter. Conversely, 3 aberrant individuals did not alter their movement rate through the year and were best fit with a linear response curve. The seasonal rate of movement model we developed suggests an average summer period of 122 days (median = 119 days, range = 96–173 days) for moose in northwestern Ontario, Canada. The rate of movement model we applied to individuals indicated 1 May as the median date for the winter-summer transition (range = 2 Apr–24 May), and the median transition from summer to winter was 25 August (range = 1 Aug–23 Oct). Wide variation in timing and duration of summer and winter seasons among individuals demonstrates potential failure of the single external variable approach to capture the suite of factors potentially influencing animal behaviors. By plotting cumulative distance moved throughout the year, we elucidated individual variation in response to known and unknown variables that affect animal movement. Accounting for variability among individuals in designation of biologically significant temporal boundaries is critical to delineation of seasonally important habitats for conservation and sustainability of healthy wildlife populations.     

Casual movement speed but not maximal locomotor capacity predicts mate searching success

Maximal locomotor performance is often used as a proxy for fitness. Maximal speed may be important under high‐threat conditions, such as during predator escape. However, animals do not always move at a speed that reflects their maximal physiological capacities when undisturbed. The physiological factors that determine the movement speed chosen by animals, such as minimization of energy use, may be independent from maximal performance. As a result, the casual speed at which individuals move when undisturbed in a given context may better represent an individual's motivation to move. The casual speed may therefore be a better predictor of fitness in natural contexts than maximal performance capacity. We tested the hypothesis that casual movement speed rather than maximal speed predicts fitness in the golden orb‐web spider, Nephila plumipes. We measured fitness in two separate contexts, mate‐searching success and the positional rank near a female. We show that casual but not maximal locomotor speed predicted both aspects of fitness. Casual speed was linearly related to maximal speed, indicating that casual speed is determined by physiological optimization. Size and metabolic scope were not related to either maximal or chosen speeds, indicating that the supply of ATP does not limit locomotor performance in this species. Overall, our results demonstrate that locomotor performance is related to fitness, but suggest that different types of performance and not necessarily maximal physiological capacities are most relevant for particular ecologically relevant tasks.     

Microtubule treadmilling: what goes around comes around

“I'll see it when I believe it” Daniel Mazia Microtubules are centrally involved in many essential cell functions, including mitosis, vesicle motility, and the control of morphogenesis. Further, they appear to be involved in the control of cell cycle progression. To carry out these tasks properly, microtubules assume a protean array of different stability states and degrees of organization and they respond rapidly to requirements of the cell by modification of their organization and stability. In the typical fibroblast cell in culture, microtubules rapidly exchange their subunits with tubulin in the cytoplasmic pool, and control of this rapid turnover appears to be essential to their intrinsic capacity to perform such tasks as the separation of chromosomes in mitosis. Microtubules are not simple equilibrium polymers, but rather, they are capable of unusual nonequilibrium dynamic behaviors. One such behavior, termed treadmilling, involving the intrinsic flow of subunits from one polymer end to the other, is created by differences in the critical subunit concentrations at the opposite microtubule ends. Treadmilling was considered by many to be an in vitro dynamic behavior that did not play an important role in microtubule function in cells. However, recent evidence has established that treadmilling is a major in vivo mechanism underlying the dynamics of microtubule arrays. BioEssays 20 :830–836, 1998. © 1998 John Wiley & Sons, Inc.     

Slaves of the environment: the movement of herbivorous insects in relation to their ecology and genotype

The majority of insect species do not show an innate behavioural migration, but rather populations expand into favourable new habitats or contract away from unfavourable ones by random changes of spatial scale. Over the past 50 years, the scientific fascination with dramatic long-distance and directed mass migratory events has overshadowed the more universal mode of population movement, involving much smaller stochastic displacement during the lifetime of the insects concerned. This may be limiting our understanding of insect population dynamics. In the following synthesis, we provide an overview of how herbivorous insect movement is governed by both abiotic and biotic factors, making these animals essentially ''slaves of their environment''. No displaced insect or insect population can leave a resource patch, migrate and flourish, leaving descendants, unless suitable habitat and/or resources are reached during movement. This must have constrained insects over geological time, bringing about species-specific adaptation in behaviour and movements in relation to their environment at a micro- and macrogeographical scale. With insects that undergo long-range spatial displacements, e.g. aphids and locusts, there is presumably a selection against movement unless overruled by factors, such as density-dependent triggering, which cause certain genotypes within the population to migrate. However, for most insect species, spatial changes of scale and range expansion are much slower and may occur over a much longer time-scale, and are not innate (nor directed). Ecologists may say that all animals and plants are figuratively speaking ''slaves of their environments'', in the sense that their distribution is defined by their ecology and genotype. But in the case of insects, a vast number must perish daily, either out at sea or over other hostile habitats, having failed to find suitable resources and/or a habitat on which to feed and reproduce. Since many are blown by the vagaries of the wind, their chances of success are serendipitous in the extreme, especially over large distances. Hence, the strategies adopted by mass migratory species (innate pre-programmed flight behaviour, large population sizes and/or fast reproduction), which improve the chances that some of these individuals will succeed. We also emphasize the dearth of knowledge in the various interactions of insect movement and their environment, and describe how molecular markers (protein and DNA) may be used to examine the details of spatial scale over which movement occurs in relation to insect ecology and genotype.     

Gastric pouches and the mucociliary sole: setting the stage for nervous system evolution

Prerequisite for tracing nervous system evolution is understanding of the body plan, feeding behaviour and locomotion of the first animals in which neurons evolved. Here, a comprehensive scenario is presented for the diversification of cell types in early metazoans, which enhanced feeding efficiency and led to the emergence of larger animals that were able to move. Starting from cup-shaped, gastraea-like animals with outer and inner choanoflagellate-like cells, two major innovations are discussed that set the stage for nervous system evolution. First, the invention of a mucociliary sole entailed a switch from intra- to extracellular digestion and increased the concentration of nutrients flowing into the gastric cavity. In these animals, an initial nerve net may have evolved via division of labour from mechanosensory-contractile cells in the lateral body wall, enabling coordinated movement of the growing body that involved both mucociliary creeping and changes of body shape. Second, the inner surface of the animals folded into metameric series of gastric pouches, which optimized nutrient resorption and allowed larger body sizes. The concomitant acquisition of bilateral symmetry may have allowed more directed locomotion and, with more demanding coordinative tasks, triggered the evolution of specialized nervous subsystems. Animals of this organizational state would have resembled Ediacarian fossils such as Dickinsonia and may have been close to the cnidarian–bilaterian ancestor. In the bilaterian lineage, the mucociliary sole was used mostly for creeping, or frequently lost. One possible remnant is the enigmatic Reissner''s fibre in the ventral neural tube of cephalochordates and vertebrates.     

Monkeys Are More Patient in a Foraging Task than in a Standard Intertemporal Choice Task

Studies of animal impulsivity generally find steep subjective devaluation, or discounting, of delayed rewards – often on the order of a 50% reduction in value in a few seconds. Because such steep discounting is highly disfavored in evolutionary models of time preference, we hypothesize that discounting tasks provide a poor measure of animals’ true time preferences. One prediction of this hypothesis is that estimates of time preferences based on these tasks will lack external validity, i.e. fail to predict time preferences in other contexts. We examined choices made by four rhesus monkeys in a computerized patch-leaving foraging task interleaved with a standard intertemporal choice task. Monkeys were significantly more patient in the foraging task than in the intertemporal choice task. Patch-leaving behavior was well fit by parameter-free optimal foraging equations but poorly fit by the hyperbolic discount parameter obtained from the intertemporal choice task. Day-to-day variation in time preferences across the two tasks was uncorrelated with each other. These data are consistent with the conjecture that seemingly impulsive behavior in animals is an artifact of their difficulty understanding the structure of intertemporal choice tasks, and support the idea that animals are more efficient rate maximizers in the multi-second range than intertemporal choice tasks would suggest.     

Modeling the emergence of migratory corridors and foraging hot spots of the green sea turtle

Environmental factors shape the spatial distribution and dynamics of populations. Understanding how these factors interact with movement behavior is critical for efficient conservation, in particular for migratory species. Adult female green sea turtles, Chelonia mydas, migrate between foraging and nesting sites that are generally separated by thousands of kilometers. As an emblematic endangered species, green turtles have been intensively studied, with a focus on nesting, migration, and foraging. Nevertheless, few attempts integrated these behaviors and their trade‐offs by considering the spatial configurations of foraging and nesting grounds as well as environmental heterogeneity like oceanic currents and food distribution. We developed an individual‐based model to investigate the impact of local environmental conditions on emerging migratory corridors and reproductive output and to thereby identify conservation priority sites. The model integrates movement, nesting, and foraging behavior. Despite being largely conceptual, the model captured realistic movement patterns which confirm field studies. The spatial distribution of migratory corridors and foraging hot spots was mostly constrained by features of the regional landscape, such as nesting site locations, distribution of feeding patches, and oceanic currents. These constraints also explained the mixing patterns in regional forager communities. By implementing alternative decision strategies of the turtles, we found that foraging site fidelity and nesting investment, two characteristics of green turtles' biology, are favorable strategies under unpredictable environmental conditions affecting their habitats. Based on our results, we propose specific guidelines for the regional conservation of green turtles as well as future research suggestions advancing spatial ecology of sea turtles. Being implemented in an easy to learn open‐source software, our model can coevolve with the collection and analysis of new data on energy budget and movement into a generic tool for sea turtle research and conservation. Our modeling approach could also be useful for supporting the conservation of other migratory marine animals.     

Whisker Movements Reveal Spatial Attention: A Unified Computational Model of Active Sensing Control in the Rat

Spatial attention is most often investigated in the visual modality through measurement of eye movements, with primates, including humans, a widely-studied model. Its study in laboratory rodents, such as mice and rats, requires different techniques, owing to the lack of a visual fovea and the particular ethological relevance of orienting movements of the snout and the whiskers in these animals. In recent years, several reliable relationships have been observed between environmental and behavioural variables and movements of the whiskers, but the function of these responses, as well as how they integrate, remains unclear. Here, we propose a unifying abstract model of whisker movement control that has as its key variable the region of space that is the animal''s current focus of attention, and demonstrate, using computer-simulated behavioral experiments, that the model is consistent with a broad range of experimental observations. A core hypothesis is that the rat explicitly decodes the location in space of whisker contacts and that this representation is used to regulate whisker drive signals. This proposition stands in contrast to earlier proposals that the modulation of whisker movement during exploration is mediated primarily by reflex loops. We go on to argue that the superior colliculus is a candidate neural substrate for the siting of a head-centred map guiding whisker movement, in analogy to current models of visual attention. The proposed model has the potential to offer a more complete understanding of whisker control as well as to highlight the potential of the rodent and its whiskers as a tool for the study of mammalian attention.     

Positive and negative signaling components involved in TNFalpha-induced NF-kappaB activation

Cell migration is involved in diverse physiological processes including embryogenesis, immunity, and diseases such as cancer and chronic inflammatory disease. The movement of many cell types is directed by extracellular gradients of diffusible chemicals. This phenomenon, referred to as "chemotaxis", was first described in 1888 by Leber who observed the movement of leukocytes toward sites of inflammation. We now know that a large family of small proteins, chemokines, serves as the extracellular signals and a family of G-protein-coupled receptors (GPCRs), chemokine receptors, detects gradients of chemokines and guides cell movement in vivo. Currently, we still know little about the molecular machineries that control chemokine gradient sensing and migration of immune cells. Fortunately, the molecular mechanisms that control these fundamental aspects of chemotaxis appear to be evolutionarily conserved, and studies in lower eukaryotic model systems have allowed us to form concepts, uncover molecular components, develop new techniques, and test models of chemotaxis. These studies have helped our current understanding of this complicated cell behavior. In this review, we wish to mention landmark discoveries in the chemotaxis research field that shaped our current understanding of this fundamental cell behavior and lay out key questions that remain to be addressed in the future.     

GPS determination of walking rates in captive African elephants (Loxodonta africana)

The movements of elephants in captivity have been an issue of concern for animal welfare activists and zoological professionals alike in recent years. In order to fully understand how movement rates reflect animal welfare, we must first determine the exact distances these animals move in the captive environment. We outfitted seven adult female African elephants (Loxodonta africana) at Disney's Animal Kingdom with collar-mounted global positioning recording systems to document their movement rates while housed in outdoor guest viewing habitats. Further, we conducted preliminary analyses to address potential factors impacting movement rates including body size, temperature, enclosure size, and social grouping complexity. We found that our elephants moved at an average rate of 0.409±0.007 km/hr during the 9-hr data collection periods. This rate translates to an average of 3.68 km traveled during the observation periods, at a rate comparable to that observed in the wild. Although movement rate did not have a significant relationship with an individual's body size in this herd, the movements of four females demonstrated a significant positive correlation with temperature. Further, females in our largest social group demonstrated a significant increase in movement rates when residing in larger enclosures. We also present preliminary evidence suggesting that increased social group complexity, including the presence of infants in the herd, may be associated with increased walking rates, whereas factors such as reproductive and social status may constrain movements. Zoo Biol 28:16–28, 2009. © 2008 Wiley-Liss, Inc.     

Overview movement as an index of anesthetic depth in humans and experimental animals

Anesthesia is used widely in animal research, but there are diverse opinions regarding acceptable anesthetic depth. Excessive anesthesia is associated with increased morbidity and mortality. Traditionally, researchers have been taught that animal movement during surgical and experimental procedures indicates that the animal is 'underanesthetized.' Complex movement, however, can be initiated and propagated within the spinal cord, with little input from supraspinal structures. For example, frogs with high spinal-cord transections still maintain the wiping reflex, whereby the hindlimb can move to the forelimb to wipe away a noxious stimulus. Rats that have been decerebrated can perform complex tasks, such as grooming. Brain-dead humans can have spontaneous movement of the arms, legs, and head. Consistent with these phenomena, emerging evidence suggests that, in anesthetized animals, movement in response to noxious stimulation is abolished primarily via anesthetic action in the spinal cord. When isoflurane, halothane, or thiopental is delivered selectively to the brain circulation in goats, substantially greater anesthetic concentrations in brain are needed to ablate movement, as compared with those required upon delivery of anesthetic to the entire body. Rats that have had a precollicular decerebration require the same isoflurane concentrations to prevent movement as compared to intact rats. Furthermore, data from both humans and animals indicate that memory and awareness are ablated at anesthetic concentrations that are < 50% of those needed to abolish movement. Collectively, these data indicate that animals can be anesthetized at depths that, although they do not abolish movement, still produce unconsciousness and amnesia.