Ceftriaxone rescues hippocampal neurons from excitotoxicity and enhances memory retrieval in chronic hypobaric hypoxia

Exposure to high altitude is known to cause impairment in cognitive functions in sojourners. The molecular events leading to this behavioral manifestation, however, still remain an enigma. The present study aims at exploring the nature of memory impairment occurring on chronic exposure to hypobaric hypoxia and the possible role of glutamate in mediating it. Increased ionotropic receptor stimulation by glutamate under hypobaric hypoxic conditions could lead to calcium mediated excitotoxic cell death resulting in impaired cognitive functions. Since glutamate is cleared from the synapse by the Glial Glutamate Transporter, upregulation of the transporter can be a good strategy in preventing excitotoxic cell death. Considering previous reports on upregulation of the expression of Glial Glutamate Transporter on ceftriaxone administration, the therapeutic potential of ceftriaxone in ameliorating hypobaric hypoxia induced memory impairment was investigated in male Sprague Dawley rats. Exposure to hypobaric hypoxia equivalent to an altitude of 7600 m for 14 days lead to oxidative stress, chromatin condensation and neuronal degeneration in the hippocampus. This was accompanied by delayed memory retrieval as evident from increased latency and pathlength in Morris Water Maze. Administration of ceftriaxone at a dose of 200 mg/kg for 7 days and 14 days during the exposure on the other hand improved the performance of rats in the water maze along with decreased oxidative stress and enhanced neuronal survival when compared to hypoxic group without drug administration. An increased expression of Glial Glutamate Transporter was also observed following drug administration indicating faster clearance of glutamate from the synapse. The present study not only brings to light the effect of longer duration of exposure to hypobaric hypoxia on the memory functions, but also indicates the pivotal role played by glutamate in mediating excitotoxic neuronal degeneration at high altitude. The therapeutic potential of ceftriaxone in providing neuroprotection in excitotoxic conditions by increasing Glial Glutamate Transporter expression and thereby enhancing glutamate uptake from the synapse has also been explored.     

A preliminary investigation of within-year growth patterns in reading and mathematics curriculum-based measures

This study examined patterns of growth across benchmark assessments for curriculum-based measures (CBM) over 2 academic years, with the twofold purpose of replicating earlier findings of growth patterns on R-CBM and conducting a preliminary investigation of growth patterns on M-CBM and CBM-Maze. The sample included 898 cases from 3rd through 5th grade over 2 academic years from one elementary school in the rural Midwest. All students participated in tri-annual benchmark assessments in which they were administered R-CBM, CBM-Maze, and M-CBM. Repeated measures analysis of variance was used to examine patterns of growth for all three measures. Students demonstrated greater R-CBM weekly growth during winter-to-spring than fall-to-winter across grade levels. Patterns for CBM-Maze and M-CBM were somewhat inconsistent across school years and grade levels. Results are discussed in terms of contextual variables that may impact within-year growth patterns and technical characteristics of CBM slopes.     

Acquisition of navigation by chimpanzees (Pan troglodytes) in an automated fingermaze task

These experiments investigated how chimpanzees learn to navigate visual fingermazes presented on a touch monitor. The aim was to determine whether training the subjects to solve several different mazes would establish a generalized map-reading skill such that they would solve new mazes correctly on the first presentation. In experiment 1, two captive adult female chimpanzees were trained to move a visual object (a ball) with a finger over the monitor surface toward a target through a grid of obstacles that formed a maze. The task was fully automated with storage of movement paths on individual trials. Training progressed from very simple mazes with one obstacle to complex mazes with several obstacles. The subjects learned to move the ball to the target in a curved path so as to avoid obstacles and blind alleys. After training on several mazes, both subjects developed a high level of efficiency in moving the ball to the target in a path that closely approached the ideal shortest path. New mazes were then presented to determine whether the subjects had acquired a more generalized maze-solving performance. The subjects solved 65–100% of the new mazes the first time they were presented by moving the ball around obstacles to the target without making detours into blind alleys. In experiment 2, one of the chimpanzees was trained using mazes with two routes to the target. One of the routes was blocked at one of many possible locations. After training to avoid the blind alley in different mazes, new mazes were presented that also had one route blocked. The subject correctly solved 90.7% of the novel mazes. When the mazes had one short and one long open route to the target the subject preferred the shorter route. When the short route was blocked, the subject solved only 53.3% of the mazes because of the preference for the shorter route even when blocked. The overall results suggest that with the training methods used the subjects learned to solve specific mazes with a trial-and-error method. Although both subjects were able to solve many of the novel mazes they did not fully develop a more general "map-reading" skill. Accepted after revision: 30 July 2001 Electronic Publication     

Executive function as a function of sub-clinical psychopathy

Some aspects of executive function are thought to be dysfunctional in psychopathic individuals. We administered a small battery of neuropsychological tests (spatial alternation task, object alternation task, and Porteus Maze) to two samples of college students and obtained a measure of psychopathy via a self-report questionnaire. Psychopathic traits were related to the tests of object alternation and Porteus Maze but not to the spatial alternation task. Our results support the hypothesis of orbitofrontal cortex (OFC) dysfunction with sparing of dorsolateral prefrontal cortex (DLPFC) in psychopathy and provide a downward extension of this theory to sub-clinical levels of psychopathy.     

Trait impulsiveness and executive function in healthy young adults

Performance-based neuropsychological tests are often used to assess planning and impulse control, but the extent to which these measures reflect trait impulsiveness or specific dimensions of trait impulsiveness is not clear. This study used the Barratt Impulsiveness Scale-11 (BIS-11; [Patton, J. H., Stanford, M. S., & Barratt, E. S. (1995). Factor structure of the Barratt Impulsiveness Scale. Journal of Clinical Psychology, 51, 768–774.]) to examine the relationship between various dimensions of trait impulsiveness and performance on several executive function tests in healthy young adults. Total BIS-11 scores correlated with performance on measures of planning and impulse control. Higher non-planning impulsiveness scores, which indicate poorer self-control and lower cognitive complexity, correlated most strongly with performance on a maze test that measures planning and impulse control (r = .58). These results provide support for the convergent validity of pencil-and-paper maze-based measures of planning and impulse control.     

Pigeons (Columba livia) plan future moves on computerized maze tasks

Planning, the internal process of formulating an organized method about one's future behavior, should be advantageous for non-human animals as well as for humans. However, little is known about this process in avian species. We examined planning processes in pigeons (Columba livia) using a computerized maze task. In Experiment 1, we found that the pigeons plan their next one step, and in some cases even correctly adjust their actions after change of goal locations, while performing on a plus-shaped maze. We also showed that the pigeons might even plan two steps on familiar, well-practiced mazes. In Experiment 2, we discovered that the subjects plan the direction they would go first before starting to solve a four-arm shuriken (a Japanese traditional throwing knife)-shaped maze. The birds also corrected their previously planned actions after change of goal locations. Our results from these experiments suggest that planning ahead is within the cognitive capacity of a "bird brain", and that it may be more widespread in the animal kingdom than has been presumed.     

The application of the first order system transfer function for fitting the 3-arm radial maze learning curve

A mathematical model is described based on the first order system transfer function in the form Y=B3∗exp(−B2∗(X−1))+B4∗(1−exp(−B2∗(X−1))), where X is the learning session number; Y is the quantity of errors, B2 is the learning rate, B3 is resistance to learning and B4 is ability to learn. The model is tested in a light-dark discrimination learning task in a 3-arm radial maze using Wistar and albino rats. The model provided good fits of experimental data under acquisition and reacquisition, and was able to detect strain differences among Wistar and albino rats. The model was compared to Rescorla-Wagner, and was found to be mutually complementary. Comparisons with Tulving’s logarithmic function and Valentine’s hyperbola and the arc cotangent functions are also provided. Our model is valid for fitting averaged group data, if averaging is applied to a subgroup of subjects possessing individual learning curves of an exponential shape.     

Assessing the interplay between fear and learning in mice exposed to a live rat in a spatial memory task (MWM)

In this study we tested the hypothesis that fear might facilitate learning when experienced contextually to the task. To this purpose, learning and memory performance of CD-1 mice in a Morris Water Maze (MWM) was assessed in the presence of a live predator (rat). Results indicate that a live predator induced specific predatory-avoidance responses, such as diving behavior and thigmotaxis. The rat-exposed group showed the most adaptive strategy, balancing anti-predator behavior and escape responses, while the rat pre-exposed group showed impairment in the initial phases of the acquisition. The probe trial revealed distinct swimming patterns but equal memory abilities in the different groups. Overall, this procedure represents a novel and easy test to assess the effects of stressful stimuli, contextually to spatial learning and memory performance, in mice.