Silver Nanoparticles Impair Cognitive Functions and Modify the Hippocampal Level of Neurotransmitters in a Coating-Dependent Manner.

Due to their potent antibacterial properties, silver nanoparticles (AgNPs) are widely used in industry and medicine. However, they can cross the brain-blood barrier, posing a risk to the brain and its functions. In our previous study, we demonstrated that oral administration of bovine serum albumin (BSA)-coated AgNPs caused an impairment in spatial memory in a dose-independent manner. In this study, we evaluated the effects of AgNPs coating material on cognition, spatial memory functioning, and neurotransmitter levels in rat hippocampus. AgNPs coated with BSA (AgNPs(BSA)), polyethylene glycol (AgNPs(PEG)), or citrate (AgNPs(Cit)) or silver ions (Ag+) were orally administered at a dose of 0.5 mg/kg b.w. to male Wistar rats for a period of 28 days, while the control (Ctrl) rats received 0.2 mL of water. The acquisition and maintenance of spatial memory related to place avoidance were assessed using the active allothetic place avoidance task, in which rats from AgNPs(BSA), AgNPs(PEG), and Ag+ groups performed worse than the Ctrl rats. In the retrieval test assessing long-term memory, only rats from AgNPs(Cit) and Ctrl groups showed memory maintenance. The analysis of neurotransmitter levels indicated that the ratio between serotonin and dopamine concentration was disturbed in the AgNPs(BSA) rats. Furthermore, treatment with AgNPs or Ag+ resulted in the induction of peripheral inflammation, which was reflected by the alterations in the levels of serum inflammatory mediators. In conclusion, depending on the coating material used for their stabilization, AgNPs induced changes in memory functioning and concentration of neurotransmitters.

A comparison of methods of assessing cue combination during navigation.

Mobile organisms make use of spatial cues to navigate effectively in the world, such as visual and self-motion cues. Over the past decade, researchers have investigated how human navigators combine spatial cues, and whether cue combination is optimal according to statistical principles, by varying the number of cues available in homing tasks. The methodological approaches employed by researchers have varied, however. One important methodological difference exists in the number of cues available to the navigator during the outbound path for single-cue trials. In some studies, navigators have access to all spatial cues on the outbound path and all but one cue is eliminated prior to execution of the return path in the single-cue conditions; in other studies, navigators only have access to one spatial cue on the outbound and return paths in the single-cue conditions. If navigators can integrate cues along the outbound path, single-cue estimates may be contaminated by the undesired cue, which will in turn affect the predictions of models of optimal cue integration. In the current experiment, we manipulated the number of cues available during the outbound path for single-cue trials, while keeping dual-cue trials constant. This variable did not affect performance in the homing task; in particular, homing performance was better in dual-cue conditions than in single-cue conditions and was statistically optimal. Both methodological approaches to measuring spatial cue integration during navigation are appropriate.

Differential organization of open field behavior in mice following acute or chronic simulated GCR exposure.

Astronauts undertaking deep space travel will receive chronic exposure to the mixed spectrum of particles that comprise Galactic Cosmic Radiation (GCR). Exposure to the different charged particles of varied fluence and energy that characterize GCR may impact neural systems that support performance on mission critical tasks. Indeed, growing evidence derived from years of terrestrial-based simulations of the space radiation environment using rodents has indicated that a variety of exposure scenarios can result in significant and long-lasting decrements to CNS functionality. Many of the behavioral tasks used to quantify radiation effects on the CNS depend on neural systems that support maintaining spatial orientation and organization of rodent open field behavior. The current study examined the effects of acute or chronic exposure to simulated GCR on the organization of open field behavior under conditions with varied access to environmental cues in male and female C57BL/6 J mice. In general, groups exhibited similar organization of open field behavior under dark and light conditions. Two exceptions were noted: the acute exposure group exhibited significantly slower and more circuitous homeward progressions relative to the chronic group under light conditions. These results demonstrate the potential of open field behavior organization to discriminate between the effects of select GCR exposure paradigms.

A novel apparatus for assessing visual cue-based navigation in rodents.

BACKGROUND: Our understanding of the neural systems that subserve navigation and spatial processing can be greatly improved through access to experimental approaches that allow for precise spatial and temporal control of the sensory information that inform these systems. Furthermore, paradigms that incorporate concurrent behavioral metrics of navigation performance in the presence of experimental manipulations provide an additional dimension in which to understand neurobiological findings. NEW METHOD: We investigate the use of a novel behavioral apparatus, the Instantaneous Cue Rotation (ICR) arena, which utilizes an augmented reality system to allow for rapid remote control of all symmetry breaking visual cues in the environment as rats perform a real-world visual cue-based navigation task. RESULTS: We present behavioral data collected using two different reward delivery systems (fixed or mobile). Rats' behavior was assessed with respect to the degree and timing with which their navigation strategies changed in response to an instantaneous rotation of all orienting visual cues in the arena. We show that rats were able to utilize projected visual cues to navigate to a cue-aligned goal both before and after the cues were rotated, and that the mobile feeder version was optimal. COMPARISON WITH EXISTING METHODS: In contrast to commonly used existing approaches for investigating environmental cues in spatial processing, the ICR does not require interrupting ongoing navigation behavior or rely on virtual reality systems that limit self-motion feedback. CONCLUSIONS: The ICR is an effective new method for dissociating the role of self-motion and environmental cues in navigation.

Evidence for idiothetic and allothetic control of thermo-orientation in feather-feeding lice.

Thermal cues are widely used by ectoparasites to find and exploit hosts. Recently, the wing louse Columbicola columbae (Phthiraptera: Ischnocera) was shown to use thermo-orientation when migrating between host microhabitats. Here, we study the control systems governing thermo-orientation by motion tracking wing lice on spatial and temporal heat gradients. As previously demonstrated, lice placed on spatial heat gradients successfully located nearby heat targets. Unilateral antennectomies were then used to remove spatial aspects of the thermal cue. These lice were still capable of locating heat targets, suggesting their response relied on tracking changes in the cue over time (idiothetic control). Course control was accomplished via angular corrections after louse body-angles deviated from the heat target. Louse behavior on temporal heat gradients provided additional evidence for idiothetic control- lice altered turn size and velocity after temperatures uniformly shifted without any spatial reference. We also show that lice are likely capable of responding to spatial aspects of the cue, consistent with allothetic control. On the spatial heat gradient, lice with two antennae were more efficient at locating heat targets as compared to those with unilateral antennectomies. Additionally, when traveling along temperature isoclines (where lice can detect spatial but not temporal aspects of the cue), lice with two antennae consistently turned towards the heat target, while those with unilateral antennectomies showed no preference. In all, we find evidence that lice can use both idiothetic and allothetic control during thermo-orientation, and likely integrate information from these two systems to guide movements on hosts.

No effect of riluzole and memantine on learning deficit following quinpirole sensitization - An animal model of obsessive-compulsive disorder.

RATIONALE: Chronic quinpirole (QNP) sensitization is an established animal model relevant to obsessive-compulsive disorder (OCD) that has been previously shown to induce several OCD-like behavioral patterns, such as compulsive-like checking and increased locomotion. OBJECTIVES: In current study we explored the effect of antiglutamatergic drugs, memantine and riluzole, on cognitive and behavioral performance of QNP sensitized rats. METHODS: During habituation phase, the rats (N = 56) were injected with QNP (0.25 mg/kg) or saline solution (every other day up to 10 injections) and placed into rotating arena without foot shocks for 50-min exploration. Active place avoidance task in rotating arena with unmarked to-be-avoided shock sector was used during acquisition phase. Rats were injected with memantine (1 mg/kg or 5 mg/kg), riluzole (1 mg/kg or 5 mg/kg) or saline solution 30 min before the trial and with QNP (0.25 mg/kg) or saline right before they were placed inside the rotating arena with 60° unmarked shock sector. Locomotion and number of entrances into the shock sector were recorded. RESULTS: QNP sensitization led to a robust deficit in place learning. However, neither memantine nor riluzole did reverse or alleviate the deficit induced by QNP. Contrarily, memantine significantly aggravated QNP induced deficit. CONCLUSIONS: The exacerbation of cognitive deficit following antiglutamatergic agents could be mediated by decreased glutamate concentration in nucleus accumbens and decreased hippocampal activation in the QNP sensitization model.

A history of adolescent binge drinking in humans is associated with impaired self-movement cue processing on manipulatory scale navigation tasks.

A binge drinking pattern of alcohol consumption has been shown to have an impact on brain structures that continue to develop into late adolescence. These same brain structures have been implicated in processing self-movement cues. The current study applies an array of existing and novel kinematic analysis techniques to characterize performance on manipulatory scale tasks to assess spatial orientation deficits associated with a history of adolescent binge drinking. Using kinematic analysis techniques, a history of adolescent binge drinking in university students was associated with disruptions in outward segment movement organization and less accurate direction and distance estimation in a dead reckoning task. Similar disruptions in performance were found in the bead maze task in the first training block; however, no group differences were observed on subsequent blocks of place training. This is the first study to demonstrate a relationship between adolescent binge drinking in humans and impaired processing of self-movement cues. This pattern of results demonstrates the potential of manipulatory-scale spatial tasks to detect differences in information processing associated with factors known to disrupt normal central nervous system development.

Brain networks underlying navigation in the Cincinnati water maze with external and internal cues.

The present study investigated the behavioural performance and the contributions of different brain regions on a spatial task performed by Wistar rats in the Cincinnati water maze (CWM) in two conditions: one where both distal and proximal visual cues were available (CWM-light group, n=7) and another where visual cues were eliminated by testing in complete darkness (CWM-dark group, n=7). There were differences in the behavioural performance. Energetic brain metabolism revealed significant differences in the infralimbic, orbitofrontal cortex and anterodorsal striatum. At the same time different brain networks were found. The CWM-light group showed a relationship between the orbitofrontal cortex and medial septum, whereas the CWM-dark group revealed three different networks involving the prefrontal cortex, ventral striatum, hippocampus and amygdala nuclei. The study shows that brain activation differs in these two conditions.

Dissociating position and heading estimations: rotated visual orientation cues perceived after walking reset headings but not positions.

This project examined the roles of idiothetic cues due to individuals' movement and allothetic cues independent of individuals' movement in individuals' estimations of their position and heading during locomotion. In an immersive virtual environment, participants learned the locations of five objects and then moved along two legs of a path before positioning the origin and the objects. Participants' estimations of their test position and their test heading were calculated based on the responded objects' locations, using a method of dissociating position estimation and heading estimation developed in this project. Results showed that when a conflicting visual orientation cue was presented after walking, participants relied on the allothetic cues (i.e., the visual orientation cue) for their heading estimation, but on idiothetic cues for their position estimation. These results indicate that after participants updated their position in terms the origin of the path (homing vector) via path integration, they estimated their heading. These results are inconsistent with the theoretical models stipulating that homing vectors are specified in terms of participants' body coordinate systems, but are consistent with the models stipulating that both homing vectors and participants' heading are specified in terms of a fixed reference direction in the environment.

Low-dose memantine-induced working memory improvement in the allothetic place avoidance alternation task (APAAT) in young adult male rats.

N-methyl-D-aspartate receptors (NMDAR) are involved in neuronal plasticity. To assess their role simultaneously in spatial working memory and non-cognitive learning, we used NMDAR antagonists and the Allothetic Place Avoidance Alternation Task (APAAT). In this test rats should avoid entering a place where shocks were presented on a rotating arena which requires cognitive coordination for the segregation of stimuli. The experiment took place 30 min after intraperitoneal injection of memantine (5, 10, 20 mg/kg b.w.: MemL, MemM, MemH, respectively) and (+)MK-801 (0.1, 0.2, 0.3 mg/kg b.w.: MK-801L, MK-801M, MK-801H, respectively). Rats from the control group were intact or injected with saline (0.2 ml/kg). Over three consecutive days the rats underwent habituation, two avoidance training intervals with shocks, and a retrieval test. The shock sector was alternated daily. The after-effects of the agents were tested on Day 21. Rats treated with low dose memantine presented a longer maximum time avoided and fewer entrances than the MemH, MK-801M, MK-801H and Control rats. The shocks per entrances ratio, used as an index of cognitive skill learning, showed skill improvement after D1, except for rats treated by high doses of the agents. The activity levels, indicated by the distance walked, were higher for the groups treated with high doses of the agents. On D21 the MK801H rats performed the memory task better than the MemH rats, whereas the rats' activity depended on condition, not on the group factor. These results suggest that in naïve rats mild NMDAR blockade by low-dose memantine improves working memory related to a highly challenging task.