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Biomedical subjects

F Morrell

Publications and source records attributed to F Morrell.

At least 37 records · Page 2Linked to original sources

Synapses on dendritic shafts exhibit a perforated postsynaptic density.

Synapses on dendritic shafts were examined in electron micrographs of serial sections obtained from the molecular layer of the rat dentate gyrus. Some of these synapses have been found to exhibit profiles of a discontinuous postsynaptic density (PSD). PSD reconstructions from serial sections were performed in a plane perpendicular to that of the sections. The results obtained indicate that profiles of discontinuous PSDs observed in random sections of dendritic shaft synapses are generated by sectioning of PSD plates that contain 1-3 holes or perforations. Earlier serial section studies of osmicated material have demonstrated that a proportion of axospinous synapses also exhibit a perforated PSD. It appears, therefore, that the presence of PSD perforations is a general phenomenon shared by subpopulations of different types of synapses, both those involving dendritic shafts and those involving dendritic spines.

Aging

Aged rats need a preserved complement of perforated axospinous synapses per hippocampal neuron to maintain good spatial memory.

Spatial working memory, which crucially depends on the structural integrity of the hippocampal formation and its afferent connections, is impaired in the most, but not all, of aged rats. This study was designed to verify whether aged animals that do not exhibit the spatial memory deficit are the ones in which the hippocampal synaptic connectivity remains preserved with advancing chronological age. Young adult rats with good spatial memory, aged rats with impaired spatial memory and equally aged rats with intact spatial memory were compared. The number of synapses per neuron was estimated in the hippocampal dentate gyrus. The most important results were obtained when axospinous synapses were divided into perforated and non-perforated ones according to the appearance of their postsynaptic density. A significant decrease in the number of perforated synapses was found in memory-impaired aged rats as compared to either young adults or aged animals without memory deficits. The number of non-perforated synapses per neuron was diminished in memory-deficient aged rats relative to young adults, but not to memory-intact aged rats. However, it was only the loss of perforated synapses which correlated with the degree of spatial memory impairment. Thus, aged rats need a preserved complement of hippocampal perforated synapses to maintain good spatial memory.

Aging

Control of scar formation in experimentally induced epilepsy.

Penfield proposed that the meningocerebral scar that forms following trauma to the brain plays an important role in the development of posttraumatic epilepsy. Although the epileptogenic scar has come to be widely accepted as a cause of epilepsy, there is no direct evidence that scar formation contributes to epileptogenesis. This current study showed that procedures that control the development of collagen in a fibroblastic scar may modify the development of epilepsy. Epilepsy induced in the guinea pig by injection of metallic aluminum powder into the cerebral cortex was used as a model of posttraumatic epilepsy. Following application of aluminum and implantation of epidural electrodes, animals received either daily injections of prednisolone or an ascorbic acid-deficient diet to block scar formation. Control animals also had an injection of aluminum, but afterward received saline injections or a normal diet. Control animals developed epileptic spikes and often exhibited focal seizures. All manifestations of epileptogenesis were markedly reduced in animals treated with prednisolone or the ascorbic acid-deficient diet. The reduction in epileptiform activity corresponded to reduced collagenous scar formation in the treated animals. Although effective when given prophylactically, prednisolone did not inhibit the activity of an already established epileptic focus whether induced by aluminum or by amygdala kindling, nor did it block pentylenetetrazol-induced seizures. The finding that epileptogenesis is blocked by two procedures that inhibit scar formation but show no evidence of a direct anticonvulsant effect, suggests that scar formation is a significant factor in epileptogenesis induced by metallic aluminum. The collagenous component appears to be more significant than the glial component of the scar.

Action Potentials

Loss of perforated synapses in the dentate gyrus: morphological substrate of memory deficit in aged rats.

Most, but not all, aged rats exhibit a profound deficit in spatial memory when tested in a radial maze--a task known to depend on the integrity of the hippocampal formation. In this study, animals were divided into three groups based on their spatial memory capacity: young adult rats with good memory, aged rats with impaired memory, and aged rats with good memory. Memory-impaired aged animals showed a loss of perforated axospinous synapses in the dentate gyrus of the hippocampal formation in comparison with either young adults or aged rats with good memory. This finding suggests that the loss of perforated axospinous synapses in the hippocampal formation underlies the age-related deficit in spatial memory.

Aging

Secondary epileptogenesis in man.

It is difficult to prove the existence of secondary epileptogenesis in man. In the majority of cases of human focal epilepsy, where the cause is likely to be trauma, infection, or vascular disease, the occurrence of additional or new epileptogenic foci is usually attributed to multiple primary injuries (maturing at different rates), or to progressive disease. Cerebral tumor is the only common cause in which the probability of multiple primary lesions is vanishingly low. Therefore, a personally followed series of cases of cerebral tumor seen as epilepsy are reviewed in which clinical, electrophysiologic, and pharmacologic data are analyzed for evidence of secondary epileptogenesis. Such evidence was found in 34% of our tumor patients. It was possible to demonstrate, in humans, the three stages of secondary epileptogenesis previously documented in animals. A pharmacologic test is described that separates the reversible from the irreversible stage of secondary epileptogenesis and allows prediction of the results of surgical removal of the primary focus.

Animals

Conditioned inhibition: selective response of single units.

Single cell activity and local field potentials in parastriate cortex of cats and rabbits were studied during a Pavlovian discrimination procedure. Cell activity was selectively modified; conditioned changes occurred in response either to the reinforced stimulus or to the unreinforced one, but not to both. Cells exhibiting conditioned alteration in response to the unreinforced stimulus are thought to participate in specialized circuits mediating conditioned inhibition.

Action Potentials

The BAER profile: a method for reporting electrophysiologic brainstem examinations in clinical practice.

We present a method for graphically reporting the results of brainstem auditory evoked response examinations on the basis of multiple parameters. The method is based on a transform that normalizes the many latency and amplitude measures obtained from the averaged evoked responses of normal subjects tested under standardized conditions. Among the advantages of the method are the simplicity of its use, the identification of disease profiles, and the isolation of relevant parameters for research and diagnosis.

Adult

Kindling in the frog: development of spontaneous epileptiform activity.

The present report is the first demonstration of the kindling phenomenon in a non-mammalian, poikilothermic species. Brief (2 sec) localized electrical stimulation was delivered to the hippocampal cortex of one hemisphere of the partially paralyzed bullfrog, Rana catesbeiana, at current levels just sufficient to elicit brief after-discharge (AD) on first application. Succeeding stimulations, once per hour, gave rise to more and more prolonged AD involving first the side stimulated (1 degree focus) and secondly the opposite hemisphere (2 degree focus). In addition to these stimulus-dependent alterations, after several hours spontaneous, paroxysmal discharges occurred in interstimulus intervals. They appeared first in the stimulated hemisphere, then as evoked spikes in the secondary hemisphere, and finally independently on the two sides. The waveshape of the spontaneous epileptiform potentials exhibited an extraordinary constancy from complex to complex which was specific to each animal. Such wave-shape coherence implies a constancy to both the anatomical substrate and the sequency of synaptic engagement each time spontaneous paroxysmal activity invades the network. The model is especially suitable for analysis of temperature-dependent biochemical events responsible for this functional transformation.

Animals

Correlation between diffuse EEG abnormalities and cerebral atrophy in senile dementia.

Thirty-five elderly patients were investigated because of clinical signs of dementia. The presence or diffuse cerebral atrophy, and its severity, were determined by the use of computed tomography (CT scan). All of the patients were also examined by electroencephalography (EEG), and the presence of diffuse abnormalities, especially diffuse slowing, was noted. Specifically, patients with normal or near-normal EEGs were compared with those with severe diffuse slowing. No correlation between the presence or severity of diffuse EEG abnormalities and the degree of cerebral atrophy as measured by CT scan was found. Though the EEG is clearly identifying physiological dysfunction of nerve cells in demented patients it does not appear to be reliable tool for the prediction of diffuse cerebral atrophy in this population.

Age Factors

Secondary epileptogenesis in frog forebrain: effect of inhibition of protein synthesis.

Secondary epileptogenesis was induced in the hippocampal cortex of the paralyzed bullfrog by means of localized, unilateral, intermittent electrical stimulation (kindling). Stimuli were designed to yield a brief but definite after-discharge. In control animals a progressive increase in after-discharge duration occurred at the 1 degree (stimulated) site and then at the 2 degrees site (contralateral hippocampus). Spontaneous epileptiform potentials (SEP's) occurred between stimuli, eventually independently on both sides. Cycloheximide (50 mg/kg) caused 88-99% reduction in protein synthesis, measured by 14C-leucine incorporation into brain protein. Cycloheximide-treated animals revealed no evidence of progressive prolongation of after-discharge duration when subjected to the kindling procedure (p = 0.1205 X 10(-7)). SEP's were reduced in the cycloheximide-treated animals, and confined to 1 degree hemisphere (p = 0.6 X 10(-10)). Since cycloheximide did not disturb normal electrogenesis or disrupt the after-discharges, this experiment distinguishes processes dependent upon electrical events from those requiring macromolecular synthesis. Protein synthesis seems critical to the emergence of spontaneous and autonomous epileptiform behavior of neural aggregates.

Animals