Silver ions are responsible for memory impairment induced by oral administration of silver nanoparticles.

Increasing use of silver nanoparticles (AgNPs) results in increased human exposure. AgNPs are able to cross brain-blood barrier and are a risk factor for the brain. Thus, we hypothesized that AgNPs exposure might affect hippocampal dependent memory, which required cognitive coordination processes. To verify the assumption, in this study we evaluated the effects of orally administered bovine serum albumin (BSA)-coated AgNPs on spatial memory, which engage cognitive coordination processes for on-going stimuli segregation. Rats following 28 days of oral administration with 1 mg/kg (n = 10) or 30 mg/kg (n = 10) BSA-AgNPs or saline, a control groups (n = 10, n = 8), were tested with an active place avoidance task in the Carousel Maze test. The study revealed significant impairment of long- and short-term memory, irrespectively of dose of AgNPs, whereas non-cognitive activity was on a similar level. We found significantly higher content of silver in the hippocampus in comparison to the lateral cortex. No silver was found in the cerebellum and the frontal cortex. The nanoSIMS analysis reveal a weak signal of silver in the hippocampus of AgNPs treated animals that should be attributed to the presence of silver in ionic form rather than AgNPs. Our findings indicate that oral exposure to a low dose AgNPs induces detrimental effect on memory and cognitive coordination processes. The presence of silver ions rather than AgNPs in different brain regions, in particular the hippocampus, suggests crucial role of silver ions in AgNPs-induced impairment of the higher brain functions.

Left ventricular false tendons: echocardiographic characteristics in the Polish population.

BACKGROUND: False tendon (FT) is described in a wide range (40% to 62%) of the examined hearts depending on age and additional heart abnormalities. On echocardiography, the range is even wider (1.6-78%), depending on study design and inclusion criteria. Ultrasonographic characteristics of left ventricular FTs in the Polish population are not well known. MATERIALS AND METHODS: Echocardiographic examinations of 1,679 consecutive patients were evaluated. All cases were classified according to American Society of Echocardiography Committee of Nomenclature and Standards Document on Identification of the Segments of the Heart Muscle. RESULTS: In our study, fibrous structures in the lumen of the left ventricle were detected in 100 (6%) subjects of the study group. The age of the subjects ranged from 16 to 87 years (mean age 47.9), 50 were males and 50 were females. In 94% of the subjects, FT was a single structure. No patient had clinically evident arrhythmia. CONCLUSIONS: In the Polish population, FT can be identified in all age groups, and the prevalence is similar to that reported in the literature.

Place avoidance tasks as tools in the behavioral neuroscience of learning and memory.

Spatial navigation comprises a widely-studied complex of animal behaviors. Its study offers many methodological advantages over other approaches, enabling assessment of a variety of experimental questions and the possibility to compare the results across different species. Spatial navigation in laboratory animals is often considered a model of higher human cognitive functions including declarative memory. Almost fifteen years ago, a novel dry-arena task for rodents was designed in our laboratory, originally named the place avoidance task, and later a modification of this approach was established and called active place avoidance task. It employs a continuously rotating arena, upon which animals are trained to avoid a stable sector defined according to room-frame coordinates. This review describes the development of the place avoidance tasks, evaluates the cognitive processes associated with performance and explores the application of place avoidance in the testing of spatial learning after neuropharmacological, lesion and other experimental manipulations.

Hippocampus-dependent retrieval and hippocampus-independent extinction of place avoidance navigation, and stress-induced out-of-context activation of a memory revealed by reversible lesion experiments in rats.

The use of reversible lesion techniques in memory research was pioneered in the laboratory of Jan Bures and Olga Buresova. We use the occasion of Jan's 75th birthday to briefly review the experimental utility of this approach. Two experiments from our current research are reported in which reversible lesioning methods are used to ask otherwise experimentally untenable questions about memory retrieval. The first experiment used intra-hippocampal injections of tetrodotoxin to temporarily inactivate the hippocampus during retrieval of a well-learned place avoidance navigation memory. This revealed that the hippocampus is necessary for place avoidance retrieval but that the extinction of place avoidance can occur independently of retrieving the memory and intact hippocampal function. The second experiment used KCl-induced cortical spreading depression in an interhippocampal transfer paradigm to demonstrate that a Y-maze memory that is learned by only one cortical hemisphere can be made to transfer to the other hemisphere by forcing the rat to swim, a unique stressful experience that occurred in a different apparatus, different behavioral context, and involved different behaviors than the Y-maze training. This demonstrates, we believe for the first time behaviorally, that memories can be activated outside of the behavioral context of their acquisition and expression in rats.

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.

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.

Spontaneous behavior of the gray short-tailed opossum (Monodelphis domestica) in the elevated plus-maze: comparison with Long-Evans rats.

We observed the spontaneous behavior of a laboratory marsupial--the gray short-tailed opossum (Monodelphis domestica)--in the elevated plus-maze (EPM) during six consecutive sessions and compared it with the behavior of Long-Evans rats. During the first exposure to the maze both species spent most of the time in the enclosed arms but opossums showed much higher frequency of entries into the open arms and stayed there longer. On the third and subsequent days opossums reduced their entries into the open arms and spent more time on the central square, where unlike rats they frequently groomed their lower belly and hind legs. During the last sessions they started spending more time in the enclosed arms. It is concluded that probably opossums, like rats show a stable anxiety evoked by open space. However, in the rat anxiety prevails over motivation to explore a new environment, while in the opossum it is initially at equilibrium with curiosity which habituates slower than in the rat. Results are discussed in the context of different ecology of the gray opossum that actively searches and hunts quickly moving insects. Thigmotaxic behavior, while strong in both species, dominates spontaneous behavior of the rat, but not opossum.

Both here and there: simultaneous expression of autonomous spatial memories in rats.

Foraging rats learned to avoid footshock that was present in a part of a circular arena that was either stable or rotating slowly in a lighted room. The rotation dissociated spatial information in the separate reference frames of the room and arena. After learning to avoid the shocked region in either condition, in the absence of shock, memory for this place was expressed by simultaneous avoidance of an area defined in the reference frame of the room as well as of an area defined in the reference frame of the rotating arena. Spatial memories in these distinct reference frames were acquired, retrieved, and extinguished autonomously.

Rodent navigation after dissociation of the allocentric and idiothetic representations of space.

Analysis of the neural mechanisms of place navigation requires isolation of the landmark dependent allocentric and self-motion related idiothetic orientation modes. To assess their importance, rats were trained on a rotating (360 degrees/min) arena to avoid foot shocks applied in either a room frame defined sector of the arena or an idiothetically defined region of the floor. Independence of the respective allocentric and idiothetic engrams was revealed by simultaneous avoidance of both locations. The possibility that idiothetic orientation was confounded by allocentric intramaze cues was examined in an apparatus consisting of an inner rotating disc surrounded by a stationary belt. As long as the rat was on the moving disc, position of the 60 degrees shock sector was stable on the disk but projected from it to different parts of the belt. When the rat moved to the belt the shock sector was now stable on the belt, but its projection to the disk travelled over its moving surface. The rat always found the shock sector in an idiothetically correct position but the mutual shifts of the disk and belt eliminated the utility of local cues like scent marks for the idiothetic solution of the task. Purely allocentric orientation was required in a place recognition task in which pressing a lever mounted on a rotating arena was rewarded only when the operandum moved through an allocentrically defined 60 degrees segment of its trajectory. Place recognition was manifest by increased bar pressing rates on approach to and inside the reward zone. These methods may reveal how hippocampal place cell activity correlates with both allocentric and idiothetic aspects of spatial orientation.

Conditioning of fear and conditioning of safety in rats.

In separate groups of rats forward and backward procedures for classical defensive conditioning were superimposed on on-going bar pressing for food. The forward conditioned stimulus elicited suppression of bar presses, indicating acquisition of fear. The backward stimulus paired with identical shock elicited behaviour typical for rats in a condition of safety and caused an increase of bar press rate. Enhancement of bar presses acquired in the course of backward conditioning was stable, immune to influences from unsignalled shocks presented in the same experimental context, and resistant to extinction when all shocks were discontinued. Properties of the employed variety of the backward conditioning procedure are discussed. When a brief shock overshadowed the onset of a backward stimulus, the remaining portion of the stimulus became a signal of safety.

Habituation of the orienting response to auditory and visual stimuli in rats trained to press a bar.

Habituation of the effects elicited by presentation of novel auditory (wide band noise) and visual (darkness) stimuli on on-going bar pressing for food was studied in 48 male hooded rats. Novel stimuli elicited a decrease of the bar press rate. This attenuating effect was the strongest on the first onset of the stimulus of a given modality and then slowly decayed during the stimulus action. The effect from the noise stimulus habituated more rapidly than that elicited by darkness. Then, noise onset enhanced bar pressing, and termination of the noise decreased the response rate. In contrast, termination of the darkness increased the response rate. The difference between auditory and visual stimuli in rapidity of change from attenuating to facilitating effects was more evident for shorter than for longer stimuli durations. Summation of data from repetitive presentations revealed an overall attenuating effect of the visual stimulus and a facilitating effect of the auditory stimulus on bar press rate.

Effects of partial lesion of dorsal hippocampal afferent and GM1 ganglioside treatment on conditioned emotional response and hippocampal afferent markers in rats.

Acquisition of the conditioned emotional response (CER) in 32 male hooded rats previously learned to press a bar for food and divided into four groups was studied. Two groups received electrolytic lesions of the dorsal hippocampal afferent and were thereafter injected either with GM1 ganglioside (30 mg/kg daily) or with buffer. Two remaining groups were sham operated and similarly injected. The partial hippocampal deafferentation evoked immediate enhancement of bar presses rate which persisted during the 2-week period of testing. CER training undertaken 2 days after surgical procedures appeared unsuccessful, whereas similar training with a cue of different modality initiated a week later resulted in acquisition of conditioned suppression of bar presses in all groups. Toward the end of training the conditioned suppression was more pronounced in lesioned than in control rats. The GM1 injections attenuated the conditioned suppression in control rats, presumably due to an antinociceptive role of ganglioside treatment. Behavioural training did not change the normal distribution pattern in cholinergic and serotonergic hippocampal afferent markers showing dorso-ventral gradient along longitudinal axis. The lesion-induced decrease pattern was also not affected. However, in contrast to previous findings in non-trained animals, the GM1 treatment was not effective in protecting against degenerative changes in the hippocampus of trained rats.

Differential effect of ketamine on the reference and working memory versions of the Morris water maze task.

The assumption that blockade of long-term potentiation by N-methyl-D-aspartate antagonists interferes with spatial memory was supported by experiments showing that 15 mg/kg ketamine impairs acquisition of navigation to a hidden platform but not to a visible platform. Higher doses were required to impair retrieval of overtrained place navigation. In a working memory version of the task, retrieval latencies were shorter than acquisition latencies with 4- to 15-min but not with 30- and 60-min delays. Latent learning was only effective with the 4-min delay. Ketamine prolonged the initial search of the hidden platform at 3 mg/kg and impaired latent learning but not active acquisition at 1.5-10 mg/kg. Comparison of behavioral and synaptic effects of ketamine suggests that long-term potentiation is a necessary condition, but not a sufficient condition, for acquisition of place navigation, because search strategy and latent place learning are impaired by ketamine doses not interfering with this synaptic phenomenon.

Differential effect of prior paradoxical sleep deprivation on conditioned taste aversion, neophobia and attenuation of neophobia to solid food in rats.

The effect of paradoxical sleep deprivation (PSD) on subsequent acquisition of conditioned taste aversion (CTA) to liquid diets is confounded by the uncertain level of thirst when using the water tank procedure. This difficulty is eliminated when examining CTA and attenuation of neophobia (AN) to solid diets. Adult male rats (n = 100) were habituated to receive their daily ration of food during a 30-min stay in a box equipped with a row of 10 feeders baited with 2-3 g pieces of moist standard diet. 24-h PSD increased neophobic rejection of novel sweet food (with added 5% saccharose), but did not influence intensity of CTA elicited by LiCl poisoning. Addition of a bitter tasting red food dye to the sweet food caused marked neophobia which was enhanced by preceding PSD. Association of this unpalatable food with LiCl elicited strong CTA which extinguished faster in the PSD-pretreated animals. On the other hand, preacquisition PSD did not influence AN to the same stimulus. Sweet food with added blue dye elicited only mild neophobia which was enhanced by preceding 24-h PSD. Preacquisition PSD did not influence AN but significantly increased CTA to blue sweet food. It is concluded that PSD can either enhance or weaken CTA and that this complex effect on food selection learning cannot be explained by PSD-induced reduction of fear.

Generalization of a conditioned inhibitor of response suppression in rats.

Following acquisition of conditioned suppression of barpresses to a visual conditiondd stimulus (CS), rats were subjected to a particular variety of differentiation training procedures. An auditory conditioned inhibitor (CI), which preceded and accompanied the CS on some trials, signaled that inescapable shock will not be given on that trial. When the CI acquired the capacity to attenuate markedly the suppressive effects of the CS presented within the CI + CS compound, the frequency dimension of the CI was varied during generalization tests. Reliable within-subjects gradients of barpress enhancement were obtained when tone test frequencies were presented alone. Frequency gradients obtained from CI variation in compound with the CS were rather flat and reflected some residual suppression of the on-going barpressing.

Conditioned inhibitor of the conditioned emotional response in rats.

Properties of a conditioned inhibitor (CI) were studied using the conditioned emotional response (CER) method. The classical defensive response (suppression of the on-going barpressing for food) was first established using 3 min of the white noise conditioned stimulus (CS) and foot shock unconditioned stimulus (US). Then the conditioned inhibitor, a 4 min house light offset, was introduced. During the last 3 min the CI was presented together with CS and not paired with the shock. The rapidly of CER training and also the efficacy of the CI training were both positively correlated with the CS intensity. The final effect of the CI + CS complex enhanced barpressing, whereas the CS alone suppressed it as before. The extinction of the CER resulted in the recovery of the regular barpressing rate during the CS and the CI + CS complex. Presentations of free shocks resulted in a temporary reinstatement of the suppressing effect of the CS and the enhancing effect of the CI + CS. The efficacy of inhibitory training depended on the alimentary motivation level.

Extinction, reinstatement and spontaneous recovery of conditioned suppression in rats and the stability of conditioned inhibitor performance.

Acquisition of the suppressive properties of a conditioned stimulus (CS), terminating with shock, and of the attenuating properties of the conditioned inhibitor (CI), signaling that shock will not be given at the end of the CS, proceed at similar rates. The attenuation of suppression exerted by the CI and the decrement of the suppression due to extinction differed in both the time course and the distribution of barpresses within the CS duration. After extinction the CS still retained some suppressing properties, which were limited to the last 20-30 s, whereas the CI attenuated the suppression throughout the duration of the CS. Extinction of the suppressive properties of the CS did not change the attenuating properties of the CI. The recovery of the suppressive properties of the CS after presentations of unsignaled reinstating shocks or after a long pause in experimental sessions was incomplete and shortlasting. Both procedures did not change the properties of the CS presented in compound with the CI.

Enhancement of bar-pressing rate in rats by the conditioned inhibitor of the CER.

The acquisition and stability of the conditioned inhibition of conditioned suppression (CER) was studied in two groups of 16 rats. The intensity of a white noise CS influenced the speed of CER acquisition and the amount of suppression. However, CS intensity exerted no effect on subsequent inhibitory training. During inhibitory training two kind of trials were presented: the CS paired with unavoidable shock and the same CS preceded and accompanied by the conditioned inhibitor (CI) consisting of offset of the house light. After only brief training the CS presented with the background of the CI lost nearly all suppressing properties, and concurently the suppressing effect of the CS paired with shock was markedly attenuated as well. At the end of training the CI typically enhanced on-going bar-pressing behavior. Some rats did not reach the required criterion of differential responding on the two kind of trials since the CS completely lost suppressing properties on regular CER trials. Differential responding of other rats was resistant to manipulations involved in frontal brain lesions. Reports of enhanced bar-pressing observed in number of CER studies were reviewed and discussed.