Daniel Klement

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.

Rats Use Hippocampus to Recognize Positions of Objects Located in an Inaccessible Space

Rat hippocampus plays a crucial role in many spatial tasks, including recognition of position of objects, which can be approached and explored. Whether hippocampus is also necessary for recognizing positions of objects located in an inaccessible part of the environment remains unclear. To address this question, we conditioned rats to press a lever when an object displayed on a distant computer screen was in a particular position (“reward position”) and not to press the lever when the object was in other positions (“nonreward positions”). After the rats had reached an asymptotic performance, the role of the dorsal hippocampus was assessed by blocking its activity with muscimol. The rats without functional dorsal hippocampus did not discriminate the reward position from the nonreward positions. Then the same rats were trained to discriminate light and dark conditions. The hippocampal inactivation did not disrupt the ability to discriminate these two conditions. It indicated that the inactivation itself had no major effect on the operant behavior and its control by visual stimuli. We conclude that rats use dorsal hippocampus for recognizing positions of objects located in an inaccessible part of the environment.

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 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.

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.

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

&NA; 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 objects features.

Overdispersion in the Place Cell Discharge—Stochastic Modelling and Inference

The paper is a case study monitoring the spiking activity of a place cell of hippocampus of a rat moving in an arena. Real data are evaluated using a new statistical methodology. Experimentally observed overdispersion suggests a doubly stochastic spatio‐temporal point process model of the time of spikes and the location of the rat. The inference of the driving intensity leads to a nonlinear filtering problem. Jump processes are used as parametric models of the driving intensity which enables the solution of the filtering problem by means of Bayesian Markov chain Monte Carlo methods. Simultaneously the parameters of the model are estimated. Model selection, numerical results and receptive field plasticity are discussed.

Operant behavior controlled by position of a moving object – a reinforcement learning model

Description It has been demonstrated that operant behavior can be controlled by spatial stimuli. In one of our experiment, rats were conditioned to press a lever for reward when a moving object was passing through a particular region of the experimental room (unpublished data). Although the stimulus was changing smoothly, the transitions between rewarded and non-rewarded condition were sudden. Consequently the animals anticipated the arrival to the rewarded zone by responding in its vicinity.