Gerald B. Biederman

Neurofibrillary degeneration, dendritic dying back, and learning-memory deficits after aluminum administration: Implications for brain aging

Abstract Increased concentrations of aluminum have been observed in the brains of patients with senile dementia and have been implicated in the etiology of that disease. This study assessed the possible behavioral and neurocytologic effects of increased brain aluminum in experimental animals. An infusion of 5 μ m aluminum (as aluminum tartrate) was made into the lateral ventricles of young adult male New Zealand white rabbits. On the 10th postoperative day, all animals were trained on a step-down active avoidance task and retested 3 days later. The aluminum-treated rabbits showed deficits on both original learning and retention of this task. Electron microscopic examination of neocortical neurons revealed the presence of 10-nm neurofilamentous tangles in aluminum-treated animals. For analysis of dendritic morphology, layer V pyramidal cells from the sensorimotor cerebral cortex were examined using the Scholl method to determine the number of dendritic branches at 20-μm intervals from the cell body. Although there were no differences in the number of processes leaving the cell body, there was a sharp and progressive decrease in the number of branches with increasing distance from the cell body. This pattern is consistent with that expected from a dying-back process.

Preference for Signaled Shock in Rats? Instrumentation and Methodological Errors in the Archival Literature

The “archival” (refereed journal or invited review) literature almost uniformly indicates that, consistent with most currently popular theories of behavior, rats prefer signaled shocks even when those shocks are un-modifiable. However, the experiments reported in this literature are here examined on the basis of technical-apparatus (instrumentation) and experimental-design (methodological) soundness. With regard to the assessment of instrumentation problems, it was found that a type of modified Skinner box used in preparations reporting strong preference for signaled shock was subject to significant unauthorized modification of shock intensity, attributable in part to the geometry of the shock grid with respect to nonconducting surfaces. Methodological analysis of the structure of the experimental design, associated with evidence in the modified Skinner box, showed that this design is invalid logically as a preference index, because of asymmetrical factors in the behaviors associated with preference and in the consequences arising from these behaviors.

Neurobehavioral development following aluminum administration in infant rabbits

Aluminum (Al) is known to be a neurotoxic agent in some species, inducing neurofibrillary tangles, dendritic atrophy, and behavioral deterioration, and has been implicated as a possible agent in human Alzheimers disease and dialysis dementia. This study was conducted to assess the neurotoxic effects of Al in infant rabbits, and to compare the effects to those previously observed to follow exposure in the adult animal. Aluminum tartrate (2 microM) or physiologic saline was injected into the right lateral ventricle of 2-day-old (day P3) New Zealand white rabbits. The animals were trained in a step-down active avoidance task on P12 and retested 1 day later. They were killed on P20, and their hippocampal CA1 pyramidal cells examined for neurofibrillary tangles or prepared with the rapid Golgi stain for an examination of dendritic development. Additional animals were similarly infused with 1 or 3 microM Al for qualitative and some quantitative observations. No overt neurologic signs were observed in the 1- or 2-microM groups, however, most of the 3-microM group died between P10 and P20. Although there were no significant differences between the 2-microM and control animals on either learning or retention of the active avoidance task, deficits in retention of the task were observed in the 3-microM group. Neurofibrillary tangles in CA1 pyramidal cells were observed with dosages of 1 microM and higher. In the 2-microM group, the pattern of dendritic arborization in CA1 pyramidal cells was consistent with that expected for cells retarded in their development. These results have implications in terms of developmental differences in the neurobehavioral effects of Al.

Preference for signaled shock phenomenon: Direct and indirect evidence for modifiability factors in the shuttlebox

The experiments reported here investigated whether unauthorized shock modification is a factor which mediates the preference for signaled shock phenomenon (PSS) in the shuttlebox. This factor appearednot to have a critical role in PSS on the basis of earlier experiments which reported that PSS occurred in the shuttle-box even when shock was made unmodifiable by scrambling. However, the scrambling used in these experiments was not complete. In Experiments I and II reported here, no PSS occurred with completely scrambled grids; the phenomenon emerged only with unscrambled shock. Experiment III reports evidence indicating a connection between directly assessed modification and PSS with unscrambled shock, with PSS emerging only when modification had begun to occur. The pattern of results from these shuttlebox experiments parallels that found in an earlier study of PSS using a symmetrical-choice, barpress preparation.

Forgetting of an operant response: physostigmine-produced increases in escape latency in rats as a function of time of injection.

Latency of a fixed ratio (FR) 3 escape response in rats was found to be a U-shaped function of the interval between training and injection of the anticholinesterase drug physostigmine, for intervals from 30 min. to 5 days between training and injection. An increase in FR 3 escape latency was found at 28 days. FR 1 escape groups produced a latency curve of a shape similar to that of the FR 3 group. These data confirm the results of earlier experiments using a different training procedure, and a different response measure. These results are consistent with the theory that the physiological correlate of rat memory lies in synaptic change.

The preference-for-signalled-shock phenomenon: Signalling shock is reinforcing only if shock is modifiable

Inescapable, unavoidable, 5-sec. shocks were preceded by 5-sec. white-noise signals contingent on previously food-trained (FR 40) bar pressing of 20 rats. Twenty yoked-control subjects receiving the same, but non-contingent, series of signals indicated that the signal was reliably reinforcing only if the shocks were delivered through an alternate, rather than scrambled, floor-grid system. Implications are discussed for previous reports of the preference for signalled shock phenomenon.

The overlearning reversal effect: A function of the non-monotonicity of the negativity of S- during discriminative training

In an automatic visual discrimination setting, rats learned two discriminations at once, one of which received four times the training of the other. After training, S could be given his choice between the more-trained (MT) and less-trained (LT) negative stimuli (S−). S’s choice of the MT S− indicates that its negativity was lower than that of the LT S−. In control groups. MTS+ was consistently chosen over LTS+. An explanation of these findings suggests that S− provides the initial cue function in discrimination. Later in training, S+ presumably assumes the cue function.

The Negative Effects of Positive Reinforcement in Teaching Children with Developmental Delay

Interactive modeling is frequently used in teaching skills to children with developmental delay. This study compared the performance of 12 children (7 males, 5 females; 4–10 years of age) each trained in two tasks, one through interactive modeling (with or without verbal reinforcement) and the other through passive observation. Results showed that passive modeling produced better rated performance than interactive modeling and that verbal reinforcement was counterproductive. These findings suggest that current instructional strategies may need to be reconsidered for children with developmental delay.

Observational learning in pigeons: The function of quality of observed performance in simultaneous discrimination

Abstract The present experiments investigated the role of quality of modeled performance on subsequent discrimination learning in pigeons and the function of observing a discriminating conspecific. Subjects either were exposed to the asymptotic performance of models proficient in a discrimination task (an erect vs. an inverted triangle) performing with few incorrect responses or observed the incremental performance of less proficient models with more error responding. Other groups of subjects in yoked compartments were exposed to pairings of stimulus and inaccessible grain at rates at which the respective models attained reinforcement. The results provide evidence for the beneficial effects of observing errors in performance; in addition, subjects exposed to apparatus operations in the absence of discriminating conspecifics appeared to benefit more from such observational experience than animals exposed to discriminating conspecifics.

Memory of conditioned food aversion follows a U-shape function in rats

Rats drinking saccharin solution for the first time were poisoned by injection of lithium chloride and then offered saccharin solution 90 min, 1, 2, 3, 7, 10 or 14 days later. The memory function was U-shaped with 90-min and 14-day groups retaining the most aversion to saccharin. Intervention with an anticholinesterase (physostigmine) failed to produce a disruption or enhancement of memory, as might have been expected from theories that the laying down of memories depends on modification of cholinergic synapses.