Aluminum induced neurofibrillary degeneration, brain electrical activity and alterations in acquisition and retention

In the early stages of an aluminum induced dementia model a positive correlation exists between the occurrence of neurofibrillary degeneration (NFD) in hippocampus, entorhinal and neocortex and the rate of conditioned avoidance response acquisition. Quantitative measurements from appropriate electronmicrographs indicate that the density of microtubules in a region of NFD is profoundly reduced. At the stage in the encephalopathy in which short-term retention and acquisition are impaired the EEG and averaged visual evoked potentials were normal. The observations suggest that a nonelectrical activity of neurons, important to the learning-memory mechanism, may be altered by the effects of aluminum chloride. The disorganization of the dendritic microtubular system is postulated to alter dendroplasmic flow and supports the hypothesis that the translocation of synaptically active agents by the cytoplasmic streaming mechanism may subserve a component of the associative learning mechanism.     

Chronic model of neurofibrillary changes induced in mature rabbits by metallic aluminum

—A slurry of aluminum powder injected into the brains of mature rabbits produced neurofibrillary changes in neurons of spinal cord and cerebrum similar to those produced by aluminum chloride, and with similar topography and rates of formation. The major difference observed with this preparation was that many rabbits survived several weeks or months before having any obvious seizures, compared to 2 to 3 weeks with aluminum chloride, and some survived with no obvious symptoms, apparently indefinitely (12 months being the longest time before sacrifice). This chronic animal model of neurofibrillary changes, induced in a mature nervous system, will allow better investigations of alterations in the biochemistry, pathology, behavior and cognition which may occur.     

Progressing encephalomyelopathy with muscular atrophy,induced by aluminum powder

The injection of aluminum powder into the cerebrospinal fluid of adult rabbits induced a slowly progressing encephalomyelopathy characterized at first by alteration of posture and then by myoclonic jerks and muscle weakness. N Neurofibrillary degeneration was the hallmark of the disease and involved most of the gray areas. Giant axonal swellings were also numerous, particularly in the proximal axonal segment of neurons of the anterior horns. In the anterior horns the number of neurons with neurofibrillary degeneration decreased with time, while the images of neuronophagia increased in number in the rabbits killed in the second and third month after aluminum injection. In these animals there were also pathologic changes in the peripheral nerves and muscles. The peripheral nerve showed wallerian-like degeneration. Furthermore, in some a animals, the presence of nodal axonal swellings and of paranodal myelin retraction were expression also of a distal axonopathy. Neurogenic muscular atrophy appeared in animals sacrificed in the second and third month after injection.     

Effects of beta blockade, PTSD diagnosis, and explicit threat on the extinction and retention of an aversively conditioned response

An aversively conditioned SC response was assessed in 18 males meeting DSM-IV criteria for chronic posttraumatic stress disorder (PTSD) and 10 trauma-exposed males who never developed PTSD. Effects of beta blockade on acquisition and retention of a conditioned response (CR) were examined by administering propranolol HCl before acquisition or following extinction trials. Retention of the CR was assessed 1 week following acquisition under conditions of non-threat and threat. Conditioned stimuli were colored circles and the unconditioned stimulus (UCS) was a "highly annoying" electrical stimulus. The propranolol failed to produce any measurable effects on acquisition or retention of the CR and there was no evidence of increased conditionability in individuals diagnosed with PTSD. One week following acquisition, the differential CR to the reinforced stimulus was evident only in the threat condition. This suggests that belief in the presence of a threat is necessary and sufficient for activating a previously established CR.     

Sexual dimorphism in passive avoidance behavior of rats: Relation to body weight,age, shock intensity and retention interval

Female rats were inferior to age- and weight-matched males in the retention of a step-through type passive avoidance response 24 and 48 hr after the learning. This sex difference could be observed at different intensities of foot shock which was used as aversive stimulus during the single learning trial. Additionally, unlike in males, retention of the passive avoidance response in the females was not the function of shock intensity. Male and female rats, however, showed similar passive avoidance if tested immediately after the learning trial. The results suggest the existence of sexual dimorphism in memory processes.     

Sexually dimorphic acquisition of a conditioned taste aversion in rats: Effects of gonadectomy,testosterone replacement and water deprivation

Sexual dimorphism was found to exist with respect to the acquisition of a conditioned taste aversion. When 0.30 meq of LiCl was used as a toxin, the proportion of male rats in whom aversion developed was greater than the proportion of females. Gonadectomy had an unclear effect on the behavior of females. However, gonadectomized males had less of a tendency to acquire the aversion than did intact males. Testosterone replacement counteracted this effect. Water deprivation, which has been shown to feminize testosterone-dependent slow extinction of a conditioned taste aversion, reduced the proportion of males in whom aversion developed. Thus, sexual dimorphism in the acquisition of this behavior depends at least in part on the presence of testosterone.     

Alterations in response properties in the lateral and dorsal terminal nuclei of the cat accessory optic system following visual cortex lesions

Summary The response properties of cells in the lateral (LTN) and dorsal (DTN) terminal nuclei of the accessory optic system (AOS) were examined in 14 cats which underwent unilateral visual cortex ablation. Following decortication, single units in the LTN and DTN no longer showed the high degree of binocular convergence characteristic of the intact animal, but instead LTN and DTN units became almost completely dominated by the contralateral eye. In addition, responsivity of LTN and DTN cells to high stimulus velocities was abolished by removal of cortical input. This decrement in high velocity response was observed in both the excitatory and the inhibitory components of the velocity response profile.While the incidence of direction selective neurons in both the LTN or the DTN was not affected by decortication, the distribution of preferred and non-preferred directions was dramatically altered in the LTN, and to a lesser extent in the DTN. In the LTN, there was a severe reduction in the number of cells which displayed maximal excitation for upward stimulus motion. Instead, most LTN units in the decorticate cat preferred downward directed stimulus motion. In the DTN, most units still preferred horizontal stimulus motion as in the intact animal, but the overall distribution of preferred directions displayed a clear downward vertical vector component. In other respects, such as receptive field size and position in visual space, on/off responses, and resting discharge rate, LTN and DTN units appeared unaffected by cortical lesions.These experiments demonstrate that the cortical input to the LTN and DTN plays a highly significant role in the formation of response properties of cells located in these nuclei. The results presented in this report indicate that the visual cortex is a major source of ipsilateral eye input, high velocity responses, and upward direction selectivity for the AOS units examined in these experiments.     

Alterations of choline acetyltransferase,phosphoinositide hydrolysis,and cytoskeletal proteins in rat brain in response to colchicine administration

Summary Colchicine, a microtubule disrupting toxin, was administered intracerebroventricularly to rats, followed by measurements of (i) the activity of choline acetyltransferase, a biochemical marker of cholinergic neurons, (ii) cytoskeletal protein concentrations, including tau, MAP-2, spectrin, and tubulin, and (iii) the activity of the second messenger-generating system, receptor-coupled phosphoinositide hydrolysis. One week after colchicine treatment there was a 60% decrease in choline acetyltransferase activity in the hippocampus, which was followed by a gradual increase to only a 29% deficit after 12 weeks. In the striatum and cerebral cortex, choline acetyltransferase activity was slightly reduced (by 13% and 19%, respectively) 1 week after colchicine treatment followed by increases to control values. The concentrations of tau and tubulin in the hippocampus were unaltered by colchicine treatment, and MAP-2 and spectrin were only slightly reduced 4 weeks after colchicine. Hippocampal phosphoinositide hydrolysis induced by norepinephrine was elevated approximately 28% 1 and 2 weeks after colchicine treatment and that induced by ibotenate was increased by 53% 2 weeks after colchicine.These results demonstrate that colchicine causes a severe depletion of choline acetyltransferase 1 week after administration. There was not a significant reduction of the concentration of any of the cytoskeletal proteins after 1 week, possibly due to the cell-selectivity of the toxic effect of colchicine, but there was a delayed, and temporary, decline of MAP-2 and spectrin concentrations. Associated with the decreased choline acetyltransferase activity after 1 week was an enhanced phosphoinositide hydrolysis in response to norepinephrine, and after 2 weeks there were enhanced responses to norepinephrine and to ibotenate. Thus, colchicine-induced toxicity results in neurotransmitter- and time-specific alterations in the activity of the phosphoinositide second messenger-generating system in the hippocampus.     

Differences between rats and undernourished preweaning, and controls in learning about a redundant stimulus during acquisition of a conditioned emotional response

Male rats were undernourished during the first three weeks of life by restricting maternal food consumption. Following nutritional rehabilitation, previously undernourished (PU) and control (C) rats were trained to operate a lever to obtain food reward on a variable interval schedule. When rates of responding had stabilised, the rats were tested for suppression of lever-pressing during the illumination of a light which preceded footshock. There were not differences between PU and C groups in the acquisition of this conditioned emotional response, nor were there differences in suppression when a redundant, tone stimulus was presented contemporaneously with the light to predict shock. When the tone was subsequently tested alone for its ability to suppress lever-pressing it was found to have acquired this property in C, but not in PU animals. In a second experiment, PU and C rats were found not to differ in their response to the tone when it was presented as a novel stimulus, nor in suppression to the tone when it was made the sole predictor of footshock. It was concluded that PU and C rats differed in learning about a stimulus predicting footshock, only when that stimulus was redundant. Among the possible explanations for this behavioural difference between PU and control rats are differences in motivation, curiosity, or strength of conditioning. These possibilities are evaluated within the context of current formal theories of conditioning.