Biomedical subjects
Publications and source records attributed to M L Shapiro.
Four cases of intrascrotal hematoma simulating testicular rupture were noted in teenagers. Careful sonographic technique allowed for the discovery of the normal testicle in a more peripheral location in the scrotum. Duplex doppler aided in confirming a normal testis in one case.
Female Sprague-Dawley rats were injected with the noncompetitive N-methyl-D-aspartate (NMDA) antagonist MK-801 or saline 30 min before daily testing in spatial working memory (WM) and reference memory (RM) procedures in an 8-arm radial maze. MK-801 impaired RM and WM acquisition but not performance when rats were trained to criterion before drug administration. Neither a 2-hr nor a 4-hr delay between the first and last 2 correct WM choices impaired long-term WM. MK-801 impaired WM performance in trained rats only when rats were tested in a new environment. Thus, 2 mechanisms may be required for relational memory: an NMDA-dependent mechanism for acquiring long-term spatial representations and an NMDA-insensitive mechanism for operating on these stored representations.
We conducted a retrospective review examining lipid profiles, creatine phosphokinase (CK) levels, and alanine aminotransferase levels (ALT) in patients receiving the combination of gemfibrozil and lovastatin. Serum lipid levels were significantly improved with therapy over those before therapy. Of the 70 patients receiving the combination, 5 experienced mild elevations in CK, 1 a mild elevation in ALT, and 1 mild elevations in both. No patient reported muscle weakness or muscle pain. The combination of these two medications appeared to be at least additive, highly effective, and well tolerated. The mean total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels decreased from 278, 306, and 180 mg% to 200, 151, and 129 mg%, respectively, and the mean high-density lipoprotein cholesterol levels increased from 34 to 40 mg%. This retrospective data analysis suggests that the combination of gemfibrozil and lovastatin may be safe in patients with normal renal function when the dosage of lovastatin is limited and when CK and ALT levels are monitored carefully.
The present experiment was designed to determine the extent to which two different mechanisms were responsible for the recovery of function produced by grafts of fetal basal forebrain tissue into the hippocampus of rats given fimbria-fornix lesions. The place fields of single units in the hippocampus were recorded as rats moved about a radial arm maze. Two measures of the discriminative stimuli identifying the place fields were determined: place stability, maze stability. In control (CON) rats, place stability was high and maze stability was low, indicating that the relevant discriminative stimuli were extra-maze cues. In rats with fimbria-fornix (FF) lesions, place stability was low and maze stability was high, indicating that the relevant discriminative stimuli came from the maze itself. In rats given grafts of fetal basal forebrain tissue (GRAFT), place stability was increased and maze stability was reduced as compared to FF rats. These results indicate that the grafts produced recovery of function through restoration of normal hippocampal unit activity, rather than by reorganization of new neural networks.
Intrahippocampal grafts of fetal basal forebrain tissue have been shown to restore several aspects of neural function, including some degree of behavioral recovery in spatial memory tasks, in rats with fimbria-fornix lesions. Place fields, the behavioral correlates of complex-spike unit activity recorded in the hippocampus of rats, are altered by fimbria-fornix lesions, and provide an important measure of the functioning circuitry of the hippocampus after grafts. To investigate the effects of grafts on hippocampal circuitry, complex-spike units were recorded while the rats traversed a radial maze. Quantitative analyses of spatial activity showed that units in normal rats had spatially clustered, reliable place fields that were stable despite alterations of the maze. In contrast, units in rats with fimbria-fornix lesions had more dispersed, less reliable place fields that were disrupted when the maze was covered or rotated. Compared to rats with fimbria-fornix lesions, rats with grafts and units with more tightly clustered, more reliable, and more stable place fields when the maze was altered. The results suggest that: (1) fimbria-fornix lesions disrupt some aspects of complex-spike place field activity; (2) the functioning of hippocampal circuitry is influenced by fetal basal forebrain grafts; and (3) the grafts may ameliorate the effects of lesions on spatial behaviors by influencing critical aspects of place field activity in the hippocampus.
The effect of hippocampal seizures in rats was assessed in two spatial memory tasks: The reference memory task was a simultaneous two-choice discrimination in a T-maze. The working memory task was a delayed conditional discrimination in a radial arm maze. In each task the hippocampus of each rat was stimulated to seizure after the presentation of the information to be remembered. In the reference memory task, hippocampal seizures did not impair acquisition, whether the stimulation was given immediately after or 4 hr after the presentation of the stimuli to be remembered. In the working memory task, hippocampal seizures did impair performance in a group of the same rats. These results support the distinction between a trial-dependent working memory system that requires hippocampal function and a trial-independent memory system that does not depend on hippocampal function.
Neural activity was recorded from local groups of hippocampal single units in rats performing a spatial-memory task. The organization of functional correlates in these neural ensembles was investigated by examining the spatial relationships among the place fields of single units in each ensemble. The distance and overlap between place fields were determined together with the tuning of cellular activity to behavioral variables, including direction, speed, and turning angle during movements within place fields. The place fields of recorded neural ensembles were significantly clustered: closer in space and considerably more overlapped than chance when compared statistically with Monte Carlo simulations. Just as single units often have significant firing in more than one distinct location in the environment (subfields), the ensembles had multiple and distinct clusters of overlapping subfields. In addition, proximity and overlap between place fields were significantly, but weakly, correlated with similarity in optimal movement tuning parameters. These results suggest that the hippocampus maintains a local organization with respect to place fields despite having no apparent large-scale isomorphism with the spatial environment. The organization of multiple, clustered place fields with correlated movement tuning properties in small neural ensembles suggests the existence of functional neural ensembles serving to encode multiple sensory and behavioral aspects of a place or event. Such an organization is similar to that observed for neocortical association areas afferent to the hippocampal system.
The ability of intrahippocampal grafts of fetal septal-diagonal band tissue, rich in developing cholinergic neurons, to ameliorate cognitive impairments induced by bilateral fimbria-fornix transections in rats was examined in three experiments using the Morris water-maze to test different aspects of spatial memory. Experiment 1. Rats with fimbriafornix lesions received either septal cell suspension grafts or solid septal grafts; normal rats and rats with lesions alone were used as controls. Sixteen weeks after surgery, the rats' spatial learning and memory were tested in the water-maze using a place test, designed to investigate place navigation performance, in which rats learned to escape from the water by swimming to a platform hidden beneath the water's surface. After 5 days of training, the rats were given a spatial probe test in which the platform was removed from the tank to test spatial reference memory. Experiment 2. The same rats used in Exp. 1 were tested in a delayed-match-to-sample, working memory version of the water-maze task. The platform was located in one of two possible locations during each trial, which was composed of 2 swims. If the rat remembered the location of the platform on the 2nd swim of a trial, it should find the platform more quickly on that swim, and thereby demonstrate working memory. Experiment 3. Prior to receiving fimbria-fornix lesions, normal rats were trained in a modification of the water-maze task using alternating cue navigation and place navigation trials (i.e., with visible or non-visible escape platforms). The retention and reacquisition of the place task and the spatial probe test were examined in repeated tests up to 6 months after the lesion and intrahippocampal grafting of septal cell suspensions. The effects of central muscarinic cholinergic receptor blockade with atropine were also tested. Normal rats performed well in both the place and spatial probe tests. In contrast, rats with fimbria-fornix lesions only were unable to acquire or retain spatial information in any test. Instead, these rats adopted a random, non-spatial search strategy, whereby their latencies to find the platform decreased in the place navigation tasks. Sixty to 80% of the rats with septal suspension or solid grafts had recovered place navigation, i.e., the ability to locate the platform site in the tank, in Exp. 1 and 3, and they showed a significantly improved performance in the working memory test in Exp. 2. Atropine abolished the recovered place navigation in the grafted rats, whereas normal rats were impaired to a lesser extent.(ABSTRACT TRUNCATED AT 400 WORDS)
Although mnemonic interpretations of hippocampal function in people have been readily accepted for many years, similar interpretations of hippocampal function in animals have received a number of challenges. This article reviews two of these challenges, shows how they were resolved in favor of some kind of mnemonic interpretation, and then suggests ways in which these types of interpretations must change in order to encompass new data.
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