Catherine Thinus-Blanc

Working memory, response selection, and effortful processing in rats with medial prefrontal lesions.

This study examined the effects of lesions of the prelimbic area of the rat prefrontal cortex on acquisition and retention of nonmatching (NMTS) and matching-to-sample (MTS) tasks. Both tasks involved a reference and a working memory component, but only working memory was impaired by the lesions. A comparison of the 2 tasks revealed quantitatively similar deficits in postoperatively trained rats. In preoperatively trained rats, however, the deficits were more important in the MTS task than in the NMTS task. In addition, an effect of interference between successive trials was observed in the NMTS task but not in the MTS task. Perseverative tendencies were observed in the MTS task only. These results suggest that prefrontal lesions induce working memory deficits as a result of poor temporal encoding and increased susceptibility to interference and impair effortful processing, such as that engaged in response selection mechanisms.

A study of exploratory behavior as an index of spatial knowledge in hamsters

This experiment investigated the role of exploration in the formation of maps of the environment. The effects of spatial rearrangement of four familiar objects in an open field on subsequent exploratory behavior were studied in hamsters (Mesocricetus auratus). During two exploratory sessions, four groups of subjects were exposed to objects in a particular spatial relation to each other and to a distal pattern. During a testing session, the control group was exposed to the same situation as during the first two sessions, and the three experimental groups were exposed to various object rearrangements. The hamsters in the experimental groups, but not those in the control group, renewed their exploration of the objects during the testing session, as measured by the number of contacts with the objects and the time spent investigating them. Further analyses of the nature of the reinvestigated objects (i.e., displaced or nondisplaced) support the hypothesis that, through exploration, a long-lasting representation of the environment is built up on the basis of the topological relations among the objects, the overall geometric structure provided by the arrangement of the objects, and the relations between the objects and extra-apparatus landmarks.

Nicotinic and muscarinic receptors in the rat prefrontal cortex: Differential roles in working memory, response selection and effortful processing

The aim of the present study was to evaluate the effects of cholinergic receptor blockade in the rat prefrontal cortex on cognitive processes. The nicotinic antagonists neuronal bungarotoxin and dihydro-β-erythroidine and the muscarinic antagonist scopolamine were injected into the prelimbic area of the prefrontal cortex. Their behavioural effects were assessed in a T-maze to test reference memory (visual discrimination task) and working memory in delayed matching (MTS) and non-matching to sample (NMTS) tasks. Neuronal bungarotoxin produced a significant decrease in working memory performance in the MTS task but not in the NMTS task. In contrast, scopolamine impaired working memory in both MTS and NMTS tasks. Reference memory was not altered by any of the cholinergic antagonists. These results demonstrate a differential role of nicotinic and muscarinic receptors in the rat prefrontal cortex. Nicotinic transmission appears to be important in delayed response tasks requiring effortful processing for response selection, while the muscarinic system is involved in general working memory processes.

Early Deficits in Spatial Memory and Theta Rhythm in Experimental Temporal Lobe Epilepsy

Patients with temporal lobe epilepsy (TLE), the most common form of epilepsy in adults, often display cognitive deficits. The time course and underlying mechanisms of cognitive decline remain unknown during epileptogenesis (the process leading to epilepsy). Using the rat pilocarpine model of TLE, we performed a longitudinal study to assess spatial and nonspatial cognitive performance during epileptogenesis. In parallel, we monitored interictal-like activity (ILA) in the hippocampal CA1 region, as well as theta oscillations, a brain rhythm central to numerous cognitive processes. Here, we report that spatial memory was altered soon after pilocarpine-induced status epilepticus, i.e., already during the seizure-free, latent period. Spatial deficits correlated with a decrease in the power of theta oscillations but not with the frequency of ILA. Spatial deficits persisted when animals had spontaneous seizures (chronic stage) without further modification. In contrast, nonspatial memory performances remained unaffected throughout. We conclude that the reorganization of hippocampal circuitry that immediately follows the initial insult can affect theta oscillation mechanisms, in turn, resulting in deficits in hippocampus-dependent memory tasks. These deficits may be dissociated from the process that leads to epilepsy itself but could instead constitute, as ILA, early markers in at-risk patients and/or provide beneficial therapeutic targets.

Encoding of geometric and featural spatial information by goldfish (Carassius auratus)

Goldfish (Carassius auratus) were trained in different place-finding tasks as a means of analyzing their ability to encode the geometric and the featural properties of the environment. Results showed that goldfish could encode and use both geometric and featural information to navigate. Goldfish trained in a maplike, or relational, procedure encoded both types of information in a single representation. In contrast, fish trained in a directly cued procedure developed 2 independent and competing strategies. These results suggest that the geometric properties of the spatial arrangement and discrete landmarks are sensitive to encoding in a maplike or relational system, whereas different sources of spatial information are encoded in a single and flexible representation of the environment.

The differences shown by C57BL/6 and DBA/2 inbred mice in detecting spatial novelty are subserved by a different hippocampal and parietal cortex interplay

Inbred C57BL/6 (C57) and DBA/2 (DBA) mice with hippocampus, posterior parietal cortex or sham lesions were placed in an open-field containing five objects and their reactivity to the displacement (spatial novelty) or the substitution (object novelty) of some of these objects was examined. C57 mice reacted to spatial novelty by exploring more the displaced than the non-displaced objects while DBA mice did not show any consistent reaction. In the highly reactive C57 strain, the peak of exploratory responses directed towards the displaced objects was completely abolished by hippocampal and posterior parietal cortex lesions. In the non-reactive DBA strain, hippocampal lesions induced an aspecific decreased interest towards the two categories of objects while posterior parietal cortex lesions did not produce any behavioral modification. The high reactivity of C57 mice to spatial change appears to be subserved by the conjunctive participation of the hippocampus and the posterior parietal cortex. Conversely, the deficit shown by DBA mice in that situation seems to be related to: (i) a poorly functional hippocampus; and (ii) the non-involvement of the posterior parietal cortes. The present data suggest that the participation of the posterior parietal cortes to the detection of spatial novelty may depend on the degree of functionality of the hippocampus.

Multiple spatial learning strategies in goldfish (Carassius auratus)

Abstract There is a considerable amount of evidence that mammals and birds can use different spatial learning strategies based on multiple learning and memory systems. Unfortunately, only a few studies have investigated spatial learning and memory mechanisms in other vertebrates. This study aimed to identify the strategies used by goldfish to solve two different spatial tasks in a series of three experiments. In experiment 1, two groups of goldfish (Carassius auratus) were trained either in a spatial constancy task (SC), in which visual cues signalled the goal indirectly, or in a directly cued task (DC) in which similar cues signalled the goal directly. Transfer tests were conducted to study the effects of discrete cue deletion on the performance in both tasks. In these transfer tests the performance of the animals trained in the DC task dropped to chance level when the cue that signalled the goal directly was removed. In contrast, the removal of any single cue did not disrupt SC performance. In experiment 2, fish trained in the SC or the DC task were trained with the goal reversed. Goldfish in the SC group needed fewer sessions to master the reversal task than DC animals. Finally, experiment 3 investigated the effects of a substantial modification of the geometrical features of the apparatus on the performance of animals trained in the SC or in the DC condition. The performance of DC goldfish was not affected, whereas the same change disrupted performance in the SC animals despite the presence of the visual cues. These results suggest that there are separate spatial learning and memory systems in fish. Whereas the DC animals used a typical guidance strategy, relying only on the cue that signalled the goal directly, SC fish relied on a strategy with the properties of an actual spatial mapping system. Thus, the comparative approach points to the generality of these learning strategies among vertebrates.

Early visual experience affects memorization and spatial representation of proprioceptive targets

FIVE subjects who had been blind from an early age and five age-matched blindfolded sighted subjects were engaged in a spatial memory task. Locations to be memorized were presented on a sagittal plane by passive positioning of the left index finger. A go signal for matching the target location with the right index finger was provided 0 or 8 s after left hand positioning. Constant errors in amplitude and direction of movement and pointing distribution observed after the longer delay differed across groups. Pointing variability was higher in the blindfolded sighted group. In addition, the main axis of pointing distributions obtained in the blindfolded sighted group were aligned with the target array for the 8 s but not the 0 s delay.1 By contrast, the main axis tended to be aligned with movement direction for blind subjects for both delays. These results suggest that memorizing a proprioceptively defined target may involve distinct spatial representations according to delay and to early visual experience.

Transfer of Spatial Knowledge from Virtual to Real Environments

The transfer of spatial knowledge from virtual to real environments is one important issue in spatial cognition research. Up to now, studies in this domain have revealed that the properties of spatial representations are globally the same in virtual and real environments, and in most cases transfer of spatial information from one kind of environment to the other occurs. Although these results suggest that virtual environments contain much of the spatial information used in real environments, it seems difficult or even impossible to draw any clear conclusion about the spatial information which is transferred and about the conditions of transfer. Being able to quantitatively and/or qualitatively predict and observe such a transfer would broaden the possibilities of training and our knowledge of the cognitive processes involved in spatial behavior. In a first step, arguments in this sense are developed on the basis of a review of some recent studies concerned with the transfer of spatial knowledge between virtual and real environments. In a second step, empirical data are reported, that illustrate the interest and limits of such studies.

Reactions to spatial and nonspatial change in two inbred strains of mice: Further evidence supporting the hippocampal dysfunction hypothesis in the DBA/2 strain

Mice belonging to the inbred C57BL/6 and DBA/2 strains were repeatedly exposed to a given spatial configuration of five objects contained in an open field. Locomotor activity, habituation of exploration, and reactivity to the displacement of some objects (spatial change) and to the substitution of a familiar object by a new one (nonspatial change) were examined. The results show that DBA mice were more active than C57 mice and that habituation developed more rapidly in the former strain. DBA mice did not react to spatial change by an increased exploration directed toward the displaced objects, whereas C57 mice showed both an increased interest for these objects and a parallel decreased interest for the nondisplaced ones. Conversely, both strains strongly reacted to non-spatial change. These results support the hypothesis that DBA mice represent a genetic model of hippocampal dysfunction. The fact that, in these and other spatial tasks, DBA mice behave as rats with dorsal lesions of the hippocampus suggests that mice from this strain reproduce more specifically the dorsal hippocampal syndrome.