Reactions to novel objects in monkeys: what does it mean to be neophobic?

Animals' reactions to novel objects vary not only with zoological taxa and their ecology but also in the types of presented stimuli, the context, and individual characteristics. Behavioral reactions can vary from extremely neophobic (avoiding novel objects) to extremely neophilic (intense exploration of novel objects); most often, a mixture of these behavioral patterns appears. In primates, reactions toward novel objects vary according to species, age, sex, population, and the types of objects. Most experiments in this field have used a free exploration design with food or non-food objects. Here, we tested the reactions of captive male rhesus macaques using various stimuli, motivation levels, rewards, and time limits. We found that the monkeys explored and manipulated novel objects in various contexts, with little evidence of a neophobic response; however, environment, types of stimuli, and other parameters of the test can significantly affect monkeys' reactions.

The role of the hippocampus in object discrimination based on visual features.

The role of rodent hippocampus has been intensively studied in different cognitive tasks. However, its role in discrimination of objects remains controversial due to conflicting findings. We tested whether the number and type of features available for the identification of objects might affect the strategy (hippocampal-independent vs. hippocampal-dependent) that rats adopt to solve object discrimination tasks. We trained rats to discriminate 2D visual objects presented on a computer screen. The objects were defined either by their shape only or by multiple-features (a combination of filling pattern and brightness in addition to the shape). Our data showed that objects displayed as simple geometric shapes are not discriminated by trained rats after their hippocampi had been bilaterally inactivated by the GABAA-agonist muscimol. On the other hand, objects containing a specific combination of non-geometric features in addition to the shape are discriminated even without the hippocampus. Our results suggest that the involvement of the hippocampus in visual object discrimination depends on the abundance of object's features.

A bell-shaped dependence between amyloidosis and GABA accumulation in astrocytes in a mouse model of Alzheimer's disease.

Functioning at the interface between the nervous and immune systems, in the amyloid-depositing brain, astrocytes become hypertrophic and accumulate around senile plaques. Moreover, hippocampal astrocytes upregulate their γ-aminobutyric acid (GABA) content and enhance tonic inhibition, likely causing local circuit imbalance. It remains, however, unclear whether this effect is hippocampus specific and how it is regulated during disease progression. Here, we studied changes in astrocytic morphology and GABA content in the frontal cortex and dentate gyrus of control and amyloid-depositing mice. Healthy aging was accompanied by a transient increase in astrocytic GABA content at middle age and region-specific alterations of soma size. In contrast, amyloid deposition caused a gradual cortex-accentuated increase in soma size. Importantly, our data uncovered a bell-shaped relationship between the mouse age and astrocytic GABA content in both brain regions. Moreover, in mice carrying an Alzheimer's disease-related mutation in presenilin 1, astrocytes accumulated GABA even in the absence of amyloidosis. These data question the proposed inhibition of astrocytic GABA synthesis as a universal strategy for treating network dysfunction in Alzheimer's disease.

Can rats solve the active place avoidance task without the room-bound cues?

The active place avoidance task is used in the research of spatial cognition. Rats are trained on a rotating arena to avoid an aversive stimulus delivered in a part of the room while being transported toward it by the arena rotation. The task tests the ability of rats to navigate with respect to distal cues in the room and to ignore confusing cues on the arena. The demand for cue segregation makes the task suitable for studying neural mechanisms responsible for cognitive coordination. An incidental observation made in our laboratory implied that overtrained rats may be able to solve the task without the room-bound cues. The aim of this study was to test this observation. The room-bound cues were hidden by switching off the lights. Rats trained only in darkness did not learn the task at all. Rats that were initially pre-trained in light performed considerably better. In a few exceptional dark sessions they even reached the level of performance observed in light. The rats needed the aversive stimuli to keep off the to-be-avoided sector. Without them, they continued their behavior, but with no spatial relationship to the to-be-avoided sector. We conclude that rats are able to solve the place avoidance task without the room-bound cues, but not as efficiently as in their presence.

Mental transformations of spatial stimuli in humans and in monkeys: rotation vs. translocation.

We studied the ability of monkeys and humans to orient in one spatial frame ("response frame") according to abstract spatial stimuli presented in another spatial frame ("stimulus frame"). The stimuli were designed as simple maps of the "response space". We studied how the transformations of these stimuli affected the performance. The subjects were trained to choose a particular position in the response frame - either on a touch screen (monkeys) or on a keyboard (humans) - according to schematic spatial stimuli presented on the stimulus screen. The monkeys responded by touching one of four circles shown in corners of a rectangle displayed on the touch screen. The correct position was signaled by the stimulus ("map") presented on the stimulus screen. The map was a complementary rectangle, but only with one circle shown ("pointer"). The position of this circle indicated the correct position in the response frame. In the first experiment we only manipulated stimuli presented on the computer screen. The "map" was originally shown in the same position and orientation as the "response pattern" but later the position and the rotation of the map on the screen were changing. Such transformations of the stimuli allow us to study the mental operations that the animals performed and how particular mental transformations mutually differed. In the second experiment we tested whether the monkeys relied more on stimuli presented on the screen or on the surrounding stable environment and objects. We compared the performance of animals in tasks with rotated virtual maps in a stable surrounding environment with the performance in tasks where we rotated the surrounding frame (computer monitor), whereas the stimuli on the screen remained stable. In the third experiment we tested human subjects in analogous tests to compare the ability and cognitive strategies of monkeys and humans in this task. We showed that the mental strategies that monkeys used for orientation in one spatial frame according to the map presented in the other spatial frame depended on the type of stimulus manipulation. We demonstrated that for monkeys there was a difference between solving "mental rotation" and "mental translocation" in this experimental design. We showed that humans were able both to mentally rotate and translocate the displayed stimuli. However, the mental rotation was more difficult than mental translocation also for them. These experiments help us to understand how the monkeys perceive the abstract spatial information, create the representation of space and how they transform the information about the position obtained from one spatial frame into another. The comparison between humans and monkeys allows us to study this cognitive ability in phylogeny.

Inertial stimuli generated by arena rotation are important for acquisition of the active place avoidance task.

The active place avoidance task is used for testing cognitive abilities in rats. A rat, placed on a rotating circular arena, should avoid an unmarked sector defined with respect to stable extra-arena cues. We hypothesized that the inertial stimuli generated by the arena rotation may contribute to the performance in the task. These stimuli provide permanent information to the rat concerning changes in its position with respect to the extra-arena cues, it means to the reference frame in which the to-be-avoided sector is defined. To test the hypothesis, we trained one group of rats on a stable arena while extra-arena cues rotated around the arena. This eliminated the inertial stimuli generated by the arena rotation while preserving other aspects of the task. Six out of seven rats from this group did not learn this modified task. The remaining rat learned it equally well as rats from a control group learned the standard active place avoidance task. After six days of training, we changed the tasks between the groups. The control rats solved the modified task as well as the standard task. We conclude that the inertial stimuli generated by the arena rotation are important for acquisition of the active place avoidance task but not for performance once the task has been mastered. We suggest that rats must perceive the distal extra-arena cues as stable in order to associate the position of the to-be-avoided sector with these cues.

Spatial task for rats testing position recognition of an object displayed on a computer screen.

We developed two spatial tasks for rats employing computer monitor for stimuli presentation. Both tasks were aimed for testing rats' ability to recognize position of a distant object. In the first task the object was stationary except moments when it jumped from one position to another. In the second task it moved continuously across the screen. Rats were trained in an operant chamber located in front of the monitor. They responded to the object position by pressing a lever for food reward. Responses were reinforced when the object was displayed in a to-be-recognized position in the first task and when it was passing through a to-be-recognized region in the second task. The to-be-recognized position as well as the to-be-recognized region had to be determined with respect to surrounding orientation cues. Responding rate of well trained rats negatively depended on the distance between the object and the to-be-recognized position/region. In the first task this relationship was apparent during a short time after the object changed its position and it held even for newly presented unfamiliar positions of the object. We conclude that in both tasks the rats recognize position of the object by estimating distance between the object and the to-be-recognized position/region. We also analyzed contribution of timing behavior to the solution of the second task.

Spatial decisions and cognitive strategies of monkeys and humans based on abstract spatial stimuli in rotation test.

We showed previously that macaque monkeys (Macaca mulatta) could orient in real space using abstract visual stimuli presented on a computer screen. They made correct choices according to both spatial stimuli (designed as an abstract representation of a real space) and nonspatial stimuli (pictures lacking any inner configuration information). However, we suggested that there were differences in processing spatial and nonspatial stimuli. In the present experiment we show that monkeys could also use as a cue abstract spatial stimuli rotated with respect to the real response space. We studied the ability of monkeys to decode abstract spatial information provided in one spatial frame (computer screen) and to perform spatial choices in another spatial frame (touch panel separated from the screen). We analyzed how the monkeys were affected by the type of training, whether they perceived the stimuli as "spatial" or "nonspatial," and which cues they used to decode them. We compared humans to monkeys in a similar test to find out which cognitive strategy they used and whether they perceive spatial stimuli in the same way. We demonstrated that there were two possible strategies to solve the task, simple "fitting" ignoring rotations and "remapping," when the stimulus was represented as an "abstract space" per se.

Analysis of sensitivity to MK-801 treatment in a novel active allothetic place avoidance task and in the working memory version of the Morris water maze reveals differences between Long-Evans and Wistar rats.

The aims of the present study were to compare the effect of subchronic administration of MK-801 on performance in the active allothetic place avoidance (AAPA) task and in the working version of Morris water maze (MWM) in Long-Evans and Wistar rats. Animals were trained for four daily sessions either in the AAPA or in the working memory version of the MWM. Wistar rats treated by MK-801 (0.1 mg/kg) showed a cognitive deficit in the AAPA task without a significant hyperlocomotion, whereas they were not impaired in the working memory version of the MWM compared to controls. Long-Evans rats treated by MK-801 (0.1 mg/kg) were not impaired either in the AAPA task or in the MWM task. Higher doses of MK-801 (0.2 and 0.3 mg/kg) produced hyperlocomotion in both strains which corresponded to an inability to solve both spatial tasks. Long-Evans rats were superior in the MWM to the Wistar rats in the groups treated with the low dose of MK-801. In conclusion, intact Wistar rats can efficiently solve both spatial tasks; however, they are more sensitive to MK-801-induced behavioural deficit. This has relevance for modeling of the schizophrenia-related deficits and for screening substances for their therapeutic potential.

Cognitive disorganization in hippocampus: a physiological model of the disorganization in psychosis.

Cognitive coordination refers to processes that organize the timing of activity among neurons without altering individual discharge properties. Coordinating processes allow neural networks to coactivate related representations and prevent the coactivation of unrelated representations. Impaired cognitive coordination, also called cognitive disorganization, is hypothesized to be the core deficit in the disorganized syndrome of schizophrenia (Phillips and Silverstein, 2003), a condition characterized by hallucinations, disorganization, and thought disorder. This disorganization hypothesis is based on the observation that schizophrenic subjects are impaired at segregating relevant and irrelevant stimuli and selectively using associations between relevant cues. We report that injecting the neural activity blocker tetrodotoxin (TTX) into one hippocampus persistently coactivated pyramidal cells in the uninjected hippocampus that initially discharged independently. In accord with the definition of cognitive disorganization, pyramidal cell firing rates only changed for 15 min and did not accompany the coactivation. The TTX-induced coactivity was maximal at gamma periods, consistent with altered gamma oscillations and disorganization in schizophrenia. A network model confirmed that increasing the coupling of weakly associated cells impairs the selective activation and inhibition of stored spatial representations. This TTX-induced cognitive disorganization correctly predicted that the same TTX injection selectively impaired the ability of rats to segregate relevant associations among distal spatial stimuli from irrelevant local stimuli (Wesierska et al., 2005). The TTX-induced coactivity of hippocampal pyramidal cell discharge has construct and predictive validity as a physiological model of psychosis-related disorganization.

Tetrodotoxin infusions into the dorsal hippocampus block non-locomotor place recognition.

The hippocampus is critical for navigation in an open field. One component of this navigation requires the subject to recognize the target place using distal cues. The experiments presented in this report tested whether blocking hippocampal function would impair open field place recognition. Hungry rats were trained to press a lever on a feeder for food. In Experiment 1, they were passively transported with the feeder along a circular trajectory. Lever pressing was reinforced only if the feeder was passing through a 60 degrees -wide sector. Thus, rats preferentially lever pressed in the vicinity of the reward sector indicating that they recognized its location. Tetrodotoxin (TTX) infusions aimed at the dorsal hippocampi caused rats to substantially increase lever pressing with no preference for any region. The aim of Experiment 2 was to determine whether the TTX injections caused a loss of place recognition or a general increase of lever pressing. A separate group of rats was conditioned in a stationary apparatus to press the lever in response to a light. The TTX injections did not abolish preferential lever pressing in response to light. Lever pressing increased less than half as much as the TTX-induced increase in Experiment 1. When these animals with functional hippocampi could not determine the rewarded period because the light was always off, lever pressing increased much more and was similar to the TTX-induced increase in Experiment 1. We conclude that the TTX inactivation of the hippocampi impaired the ability to recognize the reward place.