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J Bures

Publications and source records attributed to J Bures.

At least 37 records · Page 2Linked to original sources

Rat spatial memory tasks adapted for humans: characterization in subjects with intact brain and subjects with selective medial temporal lobe thermal lesions.

In the present paper we describe five tests, 3 of which were designed to be similar to tasks used with rodents. Results obtained from control subjects, patients with selective thermo-coagulation lesions to the medial temporal lobe and results from non-human primates and rodents are discussed. The tests involve memory for spatial locations acquired by moving around in a room, memory for objects subjects interacted with, or memory for objects and their locations. Two of the spatial memory tasks were designed specifically as analogs of the Morris water task and the 8-arm radial-maze tasks used with rats. The Morris water task was modeled by hiding a sensor under the carpet of a room (Invisible Sensor Task). Subjects had to learn its location by using an array of visual cues available in the room. A path integration task was developed in order to study the non-visual acquisition of a cognitive representation of the spatial location of objects. In the non-visual spatial memory task, we blindfolded subjects and led them to a room where they had to find 3 objects and remember their locations. We designed an object location task by placing 4 objects in a room that subjects observed for later recall of their locations. A recognition task, and a novelty detection task were given subsequent to the recall task. An 8-arm radial-maze was recreated by placing stands at equal distance from each other around the room, and asking subjects to visit each stand once, from a central point. A non-spatial working memory task was designed to be the non-spatial equivalent of the radial maze. Search paths recorded on the first trial of the Invisible Sensor Task, when subjects search for the target by trial and error are reported. An analysis of the search paths revealed that patients with lesions to the right or left hippocampus or parahippocampal cortex employed the same type of search strategies as normal controls did, showing similarities and differences to the search behavior recorded in rats. Interestingly, patients with lesions that included the right parahippocampal cortex were impaired relative to patients with lesions to the right hippocampus that spared the parahippocampal cortex, when recall of the sensor was tested after a 30 min delay (Bohbot et al. 1998). No differences were obtained between control subjects and patients with selective thermal lesions to the medial temporal lobe, when tested on the radial-maze, the non-spatial analogue to the radial-maze and the path integration tasks. Differences in methodological procedures, learning strategies and lesion location could account for some of the discrepant results between humans and non-human species. Patients with lesions to the right hippocampus, irrespective of whether the right parahippocampal cortex was spared or damaged, had difficulties remembering the particular configuration and identity of objects in the novelty detection of the object location task. This supports the role of the human right hippocampus for spatial memory, in this case, involving memory for the location of elements in the room; learning known to require the hippocampus in the rat.

Adolescent↗

Specific spatial learning deficits become severe with age in beta -amyloid precursor protein transgenic mice that harbor diffuse beta -amyloid deposits but do not form plaques.

Memory impairment progressing to dementia is the main clinical symptom of Alzheimer's disease (AD). AD is characterized histologically by the presence of beta-amyloid (Abeta) plaques and neurofibrillary tangles in specific brain regions. Although Abeta derived from the Abeta precursor protein (beta-APP) is believed to play a central etiological role in AD, it is not clear whether soluble and/or fibrillar forms are responsible for the memory deficit. We have generated and previously described mice expressing human wild-type beta-APP(751) isoform in neurons. These transgenic mice recapitulate early histopathological features of AD and form Abeta deposits but no plaques. Here we describe a specific and progressive learning and memory impairment in these animals. In the Morris water maze, a spatial memory task sensitive to hippocampal damage, one pedigree already showed significant differences in acquisition in 3-month-old mice that increased in severity with age and were expressed clearly in 6-month- and 2-year-old animals. The second transgenic pedigree displayed a milder impairment with a later age of onset. Performance deficits significantly decreased during the 6 days of training in young but not in aged transgenic animals. Both pedigrees of the transgenic mice differed from wild-type mice by less expressed increase of escape latencies after the platform position had been changed in the reversal experiment and by failure to prefer the goal quadrant in probe trials. Both pedigrees performed at wild-type level in a number of other tests (open field exploration and passive and active place avoidance). The results suggest that plaque formation is not a necessary condition for the neuronal beta-APP(751) transgene-induced memory impairment, which may be caused by beta-APP overexpression, isoform misexpression, or elevated soluble Abeta.

Aging↗

New spatial cognition tests for mice: passive place avoidance on stable and active place avoidance on rotating arenas.

Dry arenas are a convenient tool for assessing the spatial navigation abilities of rodents. In this paper, mice must avoid a punished sector of a dry arena from which they are expelled by a puff of compressed air. The position of the punished sector is defined relative to the coordinate system of the room. In a stable environment the mice can use both extramaze and intramaze landmarks to orient themselves accurately. However, when the shock area is defined by extramaze landmarks, continuous rotation of the arena at 1 rpm makes it impossible to solve the avoidance task using arena-based cues or idiothesis. The avoidance can only be solved by paying attention to extramaze cues. Our protocol tested spatial abilities on stable and rotating arenas. The acquisition of the task was manifested under both conditions by a significant improvement of performance within the first session (short-term memory component) and at the beginning of the 24-h delayed second session (long-term memory component).

Animals↗

Inactivating one hippocampus impairs avoidance of a stable room-defined place during dissociation of arena cues from room cues by rotation of the arena.

Unilateral intrahippocampal injections of tetrodotoxin were used to temporarily inactivate one hippocampus during specific phases of training in an active allothetic place avoidance task. The rat was required to use landmarks in the room to avoid a room-defined sector of a slowly rotating circular arena. The continuous rotation dissociated room cues from arena cues and moved the arena surface through a part of the room in which foot-shock was delivered. The rat had to move away from the shock zone to prevent being transported there by the rotation. Unilateral hippocampal inactivations profoundly impaired acquisition and retrieval of the allothetic place avoidance. Posttraining unilateral hippocampal inactivation also impaired performance in subsequent sessions. This allothetic place avoidance task seems more sensitive to hippocampal disruption than the standard water maze task because the same unilateral hippocampal inactivation does not impair performance of the variable-start, fixed hidden goal task after procedural training. The results suggest that the hippocampus not only encodes allothetic relationships amongst landmarks, it also organizes perceived allothetic stimuli into systems of mutually stable coordinates. The latter function apparently requires greater hippocampal integrity.

Animals↗

Substratal idiothetic navigation of rats is impaired by removal or devaluation of extramaze and intramaze cues.

The spatial orientation of vertebrates is implemented by two complementary mechanisms: allothesis, processing the information about spatial relationships between the animal and perceptible landmarks, and idiothesis, processing the substratal and inertial information produced by the animal's active or passive movement through the environment. Both systems allow the animal to compute its position with respect to perceptible landmarks and to the already traversed portion of the path. In the present study, we examined the properties of substratal idiothesis deprived of relevant exteroceptive information. Rats searching for food pellets in an arena formed by a movable inner disk and a peripheral immobile belt were trained in darkness to avoid a 60 degrees sector; rats that entered this sector received a mild foot shock. The punished sector was defined in the substratal idiothetic frame, and the rats had to determine the location of the shock sector with the use of substratal idiothesis only, because all putative intramaze cues were made irrelevant by angular displacements of the disk relative to the belt. Striking impairment of place avoidance by this "shuffling procedure" indicates that effective substratal idiothesis must be updated by exteroceptive intramaze cues.

Animals↗

Proteome study of colorectal carcinogenesis.

Development of cancer is a complex process involving multiple changes in gene expression. To unravel these alterations, a proteome approach aimed at the identification of qualitative and quantitative changes in protein composition, including their post-translational modifications, attracts great attention. Our study was focused on the identification of proteins whose amount is altered in the course of malignant transformation of colon mucosa. Proteins extracted from tissue specimens or cell lysates were separated by two-dimensional gel electrophoresis (2-DE). Comparative analyses of 2-DE protein patterns were done using computerized image analysis. Selected proteins exhibiting statistically significant abundance alterations comparing healthy and diseased tissues were identified by mass spectrometry. Globally, we have found 57 proteins that exhibited either a significant decrease or increase in amount in pathological tissues, and 18 of these were annotated by mass spectrometry. The alterations in the expression of nine proteins were common for both precancerous and neoplastic tissues suggesting their role in colon tumorigenesis. The epithelial origin of all identified spots was checked in two cell lines Caco-2 and DLD-1 originating from well-differentiated and poorly differentiated colon carcinoma, respectively.

Adenocarcinoma↗

Effect of neonatal dentate gyrus lesion on allothetic and idiothetic navigation in rats.

Goal-directed navigation is believed to be the combined product of idiothetic and allothetic orientation. Although both navigation systems require the hippocampal formation, it is probable that different circuits implement them. Examination of Long-Evans rats with dentate gyrus lesions induced by neonatal X-ray irradiation may show the dissociation of these two components of navigation. Two recently developed place avoidance tasks on a rotating circular arena were used to test this hypothesis. In the first test, the position of the punished area is stable in the room frame but is permanently changing on the surface of the arena. This task requires the rat to use allothetic orientation and to disregard idiothetic orientation. In the second test, the prohibited area is fixed in the coordinate system of the arena and the experiment is conducted in complete darkness, forcing the rat to rely exclusively on idiothesis supported by substratal cues. The results suggest that the dentate gyrus lesion interferes less with idiothetic orientation than with allothetic orientation. In addition, an attempt was made to control the number of developing granule cells by exact timing of a single high dose of perinatal irradiation, and to measure the ensuing behavioral deficits. Rats irradiated at 6, 18, or 24 h after birth were tested as adults in the Morris water maze. Irradiated animals showed significant, but highly variable, learning deficit, but histological examination indicated that the granule cell loss did not correlate with the degree of behavioral impairment.

Animals↗

Transient sex differences in the between-sessions but not in the within-session memory underlying an active place avoidance task in weanling rats.

Spatial abilities were tested in male and female rats by training them to avoid an area in which there was a mild footshock while the arena rotated at 1 revolution/minute. The to-be-avoided area was stable in the coordinates of the room, so extramaze landmarks had to be used for accurate navigation, as the rotation made intramaze cues and substrate-based path integration useless for the avoidance. From Postnatal Day (PD) 19, rats were trained for 22 consecutive days. When the shock area was the same across sessions male rats reached optimal performance on PDs 23-24, 10 days before female rats, but when the location of the shock changed daily there were no sex differences. The results indicate that there are separate memory components underlying spatial competence: a within-session component that develops similarly in male and female rats and a between-sessions component that lasts at least 24 hr and appears earlier in male than in female rats.

Animals↗

Inflammatory response to acute myocardial infarction complicated by cardiogenic shock.

We report a case of a 60-year-old man with acute myocardial infarction (AMI) treated using thrombolysis, and complicated by cardiogenic shock (CS). Plasma interleukin (IL) 1 beta, IL 6, IL 8, tumor necrosis factor alpha (TNF alpha), and soluble adhesion molecule (sICAM 1, sE-selectin) levels were measured at 3-h intervals. This observation showed the effect of AMI and CS on the plasma interleukin levels. Remarkable changes were found in the plasma TNF alpha level, which reached two significant peaks. The peak of the first elevation caused by AMI (80.11 pg/ml, vs. normal value 4.35 pg/ml, SD 21.3 pg/ml) was seen 6 h after the onset of the symptoms. After the period of significant decrease, TNF alpha level was increasing until the end of the observation period because of CS (the last TNF alpha level was 204.1 pg/ml). The plasma IL 1 beta level was continually increased during the period of observation (maximal IL 1 beta level 32.1 pg/ml, normal value < 10 pg/ml). The plasma IL 6 level reached the first peak caused by AMI nine hours after the onset of the symptoms (362.85 pg/ml, normal value (10 pg/ml). Because of CS, after the short period of decrease, the plasma IL 6 level was increasing until the end of the observation period (the last IL 6 level was 859.61 pg/ml). The plasma IL 8 level was also elevated throughout the time of observation (max. value 1652 pg/ml, vs. normal value < 30 pg/ml). The soluble adhesion molecule levels (sE-selectin and sICAM 1) were elevated throughout the period of observation without any significant peak.

Cell Adhesion Molecules↗

[Diagnosis of Helicobacter pylori with the 13C-labeled urea breath test: study methodology].

Helicobacter pylori is one of the most common causes of chronic bacterial infection in humans, and it is associated with many diseases of the upper gastrointestinal tract. The 13C urea breath test (13C-UBT) is a simple, non-invasive and global test for Helicobacter pylori detection. The test reflects the hydrolysis of 13C-labelled urea by Helicobacter pylori urease. The 13C-UBT is the gold standard test for Helicobacter pylori infection. Since the original description (in 1987) several modifications of 13C-UBT have been published to simplify and optimise the test. However, neither Standardised European Protocol nor Standard US Protocol were accepted. This paper gives the methodology of the 13C-UBT based on eur own study and on the review of the literature.

Breath Tests↗

Passive and active place avoidance as a tool of spatial memory research in rats.

A modified model of the arena described by Bures et al. (Bures J, Fenton AA, Kaminsky Y, Zinyuk L. Place cells and place navigation, Proc. Natl. Acad. Sci. USA. 1997a;94:343-350) was applied to the place learning of adult male rats in two different avoidance paradigms. In the passive avoidance task rats exploring a stationary circular arena had to avoid a 60 degrees sector entering of which was punished by mild footshocks. Intramaze as well as extramaze cues could be used for adequate solution of this task. In the active avoidance paradigm rats were trained to avoid a room frame defined sector (e.g. North-East) of a slowly rotating arena the movement of which forced the animals to rely on extramaze cues and to ignore intramaze information. Rats had to find an active solution of the task since otherwise they were passively transported into the room frame defined punished zone. The suitability of these tasks for testing spatial abilities of rats is discussed.

Animals↗

Functional inactivation of dorsal hippocampus impairs active place avoidance in rats.

This paper assesses the contribution of hippocampus to the spatial orientation of Long-Evans rats in a new place avoidance task. The animals learn to avoid a mild footshock in a segment of a rotating arena. Since the punished region is defined in the coordinate system of the stationary room the subject is forced to move away from the prohibited segment even if it is immobile. After bilateral injection of tetrodotoxin (5 ng in 1 microl of saline) into the dorsal hippocampus rats were not able to avoid the punished place while a similar injection of saline did not affect performance. The results suggest the task is suitable for assessing the hippocampus-dependent spatial abilities of laboratory rodents.

Animals↗

Understanding hippocampal activity by using purposeful behavior: place navigation induces place cell discharge in both task-relevant and task-irrelevant spatial reference frames.

Continuous rotation of an arena in a cue-rich room dissociates the stationary room-bound information from the rotating arena-bound information. This disrupted spatial discharge in the majority of place cells from rats trained to collect randomly scattered food. In contrast, most place cell firing patterns recorded from rats trained to solve a navigation task on the rotating arena were preserved during the rotation. Spatial discharge was preserved in both the task-relevant stationary and the task-irrelevant rotating reference frames, but firing was more organized in the task-relevant frame. It is concluded that, (i) the effects of environmental manipulations can be understood with confidence only when the rat's purposeful behavior is used to formulate interpretations of the data, and (ii) hippocampal place cell activity is organized in multiple overlapping spatial reference frames.

Animals↗

Place recognition monitored by location-driven operant responding during passive transport of the rat over a circular trajectory.

Spatial memory of animals is usually tested in navigation tasks that do not allow recognition and recall processes to be separated from the mechanisms of goal-directed locomotion. In the present study, place recognition was examined in rats (n = 7) confined in an operant chamber mounted on the periphery of a slowly rotating disk (diameter 1 m, angular velocity 9 degrees /s). The animals were passively transported over a circular trajectory and were rewarded for bar pressing when they passed across a 60 degrees -wide segment of the path. This segment was recognizable with reference to room landmarks visible from the operant box. Responding defined in the coordinate system of the room increased when the chamber entered the 60 degrees -wide approach zone, culminated at the entrance into the reward sector, was decreased inside it by eating the available reward, and rapidly declined to zero at the exit from this zone. When reward was discontinued, the skewed response distribution changed into a symmetric one with a maximum in the center of the reward sector. With advancing extinction, the response peak in the reward sector decreased in most rats proportionally to the overall decline of bar pressing. The rewarded and nonrewarded response patterns indicate that passively transported rats can recognize their position in the environment with an accuracy comparable to that of actively navigating animals and that location-driven operant responding can serve as a useful tool in the analysis of the underlying neural mechanisms.

Animals↗

Continuous place avoidance task reveals differences in spatial navigation in male and female rats.

A new place navigation test was used to estimate the spatial orientation abilities of male and female rats. Animals had to avoid a room frame defined area on a rotating arena, entering of which was punished by mild footshock, i.e. rats had to avoid the same place in the room but different parts of the floor, which was rotated through the punished zone. Because of the rotation of the arena (one revolution per min), animals could not rely on intramaze cues and only extramaze landmarks could be used for accurate navigation. During 8 consecutive days rats were exposed to daily 40-min sessions, consisting of 20-min acquisition and 20-min extinction (shock discontinued). The position of the punished sector centered around one of the four mutually perpendicular azimuths was daily changed in a predetermined sequence. The results showed no male female differences during acquisition and better performance of males during extinction. The performance of females was not affected by estral cycle-related hormonal changes. The findings are discussed in the light of controversial results of research into sex differences in spatial abilities.

Animals↗

Differential expression of the Ca2+ binding S100A6 protein in normal, preneoplastic and neoplastic colon mucosa.

The expression of calcium-binding protein S100A6 was investigated in normal colon tissue, in colon adenomas and in colorectal carcinomas. Using an immunoblotting approach we detected four S100A6 variants with Mwt of 10 kDa and pI of 5.05 (isoform I), 5.15 (isoform II), 5.23 (isoform III) and 5.32 (isoform IV) that were differentially expressed in the analysed samples. The quantitative examination of S100A6 variant expression in 25 pairs of colorectal carcinoma and matched control mucosa proved a statistically significant increased abundance of S100A6 isoforms I (P = 0.004) and III (P = 0.025) in malignant tissue, and conversely, an increased level of S100A6 isoform IV in healthy tissue (P = 0.022). The expression of isoforms I and III and the loss of isoform IV were also observed in colon cancer cell lines. In addition, the immunohistochemical study of 16 primary colorectal carcinomas revealed both in the non-paired Student t-test and in the Mann Whitney test the statistically significant accumulation of S100A6 protein (P < 0.001) in the invasive margin of the tumour. The immunohistochemical analysis of S100A6 protein in polyps differing in clinical severity gave a strong staining that was maximal in dysplastic lesions. Thus, our results indicate a possible, statistically significant correlation (non-paired Student t-test P = 0.036) between S100A6 expression and colon carcinoma progression.

Adenoma↗

The place preference task: a new tool for studying the relation between behavior and place cell activity in rats.

This study describes a task that combines random searching with goal directed navigation. The testing was conducted on a circular elevated open field (80 cm in diameter), with an unmarked target area (20 cm in diameter) in the center of 1 of the 4 quadrants. Whenever the rat entered the target area, the computerized tracking system released a pellet to a random point on the open field. Rats were able to learn the task under light and in total darkness, and on a stable or a rotating arena. Visual information was important in light, but idiothetic information became crucial in darkness. Learning of a new position was quicker under light than in total darkness on a rotating arena. The place preference task should make it possible to study place cells (PCs) when the rats use an allothetic (room frame) or idiothetic (arena frame) representation of space and to compare the behavioral response with the PCs' activity.

Animals↗