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Biomedical subjects

G A Clark

Publications and source records attributed to G A Clark.

At least 37 records · Page 2Linked to original sources
PubMed1988

Parallel processing of short-term memory for sensitization in Aplysia.

How is the short-term memory for a single form of learning distributed among the various elements of a neuronal circuit? To answer this question, we examined the short-term memory for sensitization, using the siphon component of the defensive gill- and siphon-withdrawal reflex. We found that the memory for short-term sensitization is represented by at least four sites of circuit modification, each involving a different type of plasticity. These include (1) presynaptic facilitation of the sensory neuron connections onto both interneurons and motorneurons; (2) presynaptic inhibition at the connections of the L30 inhibitory neurons onto the excitatory interneuron L29; (3) posttetanic potentiation of the excitatory connections made by L29 onto a specific subclass of siphon motorneurons, the LFS cells; and (4) an increase in the tonic firing rate of the LFS siphon motor neurons, resulting in neuromuscular facilitation. Each of the heterosynaptic changes seems to involve a common modulatory transmitter and to utilize a common second messenger system. Moreover, each of these sites seems capable of encoding a different component of the short-term memory. Facilitation of the connections of sensory neurons should contribute to the increase in amplitude of the response; the disinhibition of the L29 interneurons and the posttetanic potentiation at L29 synapses should contribute to an increase in the duration of the response; and the increase in tonic firing of the LFS subclass of siphon motor neurons seems capable of contributing both to an increase in response amplitude and to changes in response topography.

Animals↗
PubMed1986

Poor growth prior to early childhood: decreased health and life-span in the adult.

Previous studies in animal populations have shown that stunted neural and thymolymphatic growth early in development may result in permanently impaired neural and immune function, decreased body growth, vertebral wedging, and decreased life-span. In the human adult, small vertebral neural canal (VNC) diameters may reflect early stunted neural and immune development and impaired function that leads to decreased health (inferred by greater vertebral wedging) and life-span in the adult. VNC, which complete their growth by early childhood (age 4), are markers of early development in adults. On the other hand, features following general body growth, such as height, weight (represented here by vertebral body height) continues to grow until young adulthood. They are less reliable, because they readily experience catch-up growth (even in chronically stressed populations) and, unlike VNC, may mask poor early growth. To test associations between early growth and adult health and life-span in humans, we measured 2,060 VNC, vertebral heights, vertebral wedging, nerve-root tunnel lengths, severity of vertebral osteophytosis, and ages at death in 90 adult (aged 15-55 years) prehistoric skeletons (950-1300 A.D.). Tibial lengths were also measured in a subsample (n = 30). Multivariate, bivariate, and nonparametric analyses showed that small VNC are significantly associated with greater vertebral wedging and decreased life-span (P less than 0.05-0.00001). VNC are independent of vertebral body heights and tibial lengths (general body growth). VNC, but not statural components, are useful in predicting adult health, presumably because they reflect neural and immune development and do not readily experience catch-up growth. Thus, longitudinal retrospective measures of early growth and adult health were systematically linked within individuals regardless of confounding factors operating over the 350-year time period. Since this research was completed, this model has repeatedly been independently confirmed in four living urban industrial populations. Longitudinal retrospective analysis was employed together with direct measures of VNC, neural and immune function. Together these results suggested that it may be essential to improve growth prior to early childhood in order to maximize adult health and life-span.

Adolescent↗
PubMed1986

Rapid extraction of plasmids from Clostridium perfringens.

Two rapid methods were evaluated for their extraction of plasmids from Clostridium perfringens. The first method involved lysis of 1 to 2 ml of C. perfringens culture by treatment with hyaluronidase, lysozyme, and sarcosyl. DNA, extracted with phenol-chloroform, was treated with RNase, boiled, and electrophoresed in a 1.2% agarose gel. The second method involved lysis of 2 ml of culture by lysozyme treatment and extraction with alkaline sodium dodecyl sulfate (SDS). Extracted DNA was treated with RNase, boiled, and electrophoresed in a 0.7% agarose gel. Of 57 strains of C. perfringens analyzed by both extraction procedures, 11 were shown to have plasmids by the alkaline SDS method which were missed by the phenol-chloroform extraction method. These new plasmids were of higher molecular mass and ranged up to 68 megadaltons. Use of the DNase inhibitor diethyl pyrocarbonate did not further improve the yield of plasmid DNA. An additional 159 isolates of C. perfringens screened by the alkaline SDS method revealed plasmids up to 80 megadaltons in mass and an overall plasmid carriage rate of 69%.

Clostridium perfringens↗
PubMed1985

Can infant malnutrition cause adult vertebral stenosis?

Does infant malnutrition produce smaller adult spinal canals? Lumbar and thoracic vertebrae (n X 1073), from a prehistoric American Indian population (15-55 yrs of age), were measured for anteroposterior (AP) and transverse (TR) vertebral canal sizes, nerve root tunnel (intervertebral foramen) widths (NRT), vertebral heights (VH), vertebral osteophytosis (VO), and tibial lengths. They underwent a dietary change from hunting-gathering, protein rich (PR), to maize agriculture, protein deficient (PD), between 950 and 1300 A.D. Multivariate analyses controlled for age, sex, culture, NRT, VH, VO, and wedging. Canal size was significantly smaller in the PD. AP diameters were generally and highly correlated with NRT, and thus both spinal stenosis and sciatica may have a developmental basis. Canal size was independent of statural components. Consequently, canal size is a most powerful tool in assessing the presence infant malnutrition. Moreover, perhaps the association between canal size and low-back pain (LBP) found in living populations has been underestimated, and this component of LBP is preventable.

Adult↗
PubMed1984

Effects of lesions of cerebellar nuclei on conditioned behavioral and hippocampal neuronal responses.

Rabbits were overtrained using classical conditioning of the rabbit nictitating membrane (NM)/eyelid response. Unilateral electrolytic lesions were then made through electrodes previously implanted in dentate and interpositus cerebellar nuclei ipsilateral to the trained (left) eye. Lesions caused a complete or near-complete abolition of conditioned behavioral responses on the ipsilateral side, but had no effect on unconditioned responses to corneal airpuff. When training was switched to the contralateral (right) side, animals learned within the first few trials, but did not relearn when training was returned to the left (lesioned) side. Control animals in which lesions spared the deep nuclei showed no such learning deficits. Lesions of cerebellar nuclei also abolished conditioned increases in hippocampal CAl neural activity evoked by the tone conditioned stimulus in this paradigm. As with the behavior, training on the right (non-lesioned) side reinstated the conditioned neuronal response within the first few trials of training, even though behavioral responding on lesioned side showed little or no improvement. These results indicate that the cerebellum is an essential structure for the behavioral expression of learning, and plays an important role in the generation of conditioned hippocampal responses observed in this paradigm.

Animals↗
PubMed1984

Increased responsivity of dentate granule cells during nictitating membrane response conditioning in rabbit.

We examined the responsivity of dentate gyrus granule cells to perforant path stimulation during classical conditioning of the rabbit nictitating membrane response. Dentate field potentials elicited by perforant path stimulation were recorded during training to test for changes in granule cell responsivity. Results showed above-baseline increases in dentate population spike amplitudes over the course of training in paired but not unpaired animals. In addition, population spike amplitudes were smaller when elicited during tone presentations in both paired and unpaired animals than between trials when no conditioning stimuli were present. While alternative interpretations remain, these results provide preliminary evidence that processes similar to long-term potentiation may occur in the hippocampus during behavioral conditioning.

Action Potentials↗
PubMed1984

Branch-specific heterosynaptic facilitation in Aplysia siphon sensory cells.

Aplysia siphon sensory cells exhibit heterosynaptic facilitation of transmitter release during both sensitization and classical conditioning of the siphon withdrawal response. In the present study, we asked whether facilitation must invariably enhance transmission at all terminals of a neuron or whether facilitation can instead occur at one set of terminals without also occurring at other terminals of the same cell. To examine this question, we compared effects of local application of serotonin and of connective stimulation on transmission at central and peripheral branches of single sensory cells. We found that heterosynaptic facilitation can be branch-specific and can occur at either central or peripheral synapses independently. We also found that siphon sensory cells exhibit homosynaptic post-tetanic potentiation, allowing us to compare effects of hetero- and homosynaptic facilitation in the same cells. By contrast to heterosynaptic facilitation, homosynaptic facilitation occurs concomitantly at both central and peripheral synapses of siphon sensory cells. Thus, while both heterosynaptic and homosynaptic facilitation involve increases in transmitter release from sensory neuron terminals, heterosynaptic facilitation provides a greater specificity and flexibility in the modification of synaptic connections.

Journal Article↗
PubMed1983

Early undernutrition impairs hippocampal long-term potentiation in adult rats.

Following high-frequency stimulation of hippocampal dentate granule cells, potentiation was difficult to achieve in undernourished animals, showed a significant decline within 3 to 6 hr, and was completely absent at 24 hr. Further trains of stimulation resulted in only small benefits in undernourished animals. Coupled with previously reported morphological and behavioral deficits, these findings indicate a marked hippocampal dysfunction resulting from early undernutrition and provide a potentially valuable approach for relating nutritionally induced behavioral impairments to brain function.

Animals↗
PubMed1982

Initial localization of the memory trace for a basic form of learning.

Electrophysiological recording of neuronal unit activity during paired training trials from various regions of the ipsilateral cerebellum in rabbits well trained in the classically conditioned eyelid/nictitating membrane response have revealed both stimulus-evoked responses and responses that form an amplitude/temporal model of the learned behavioral response. Ablation of the ipsilateral, lateral cerebellum completely and permanently abolished the behavioral conditioned response in well-trained animals but had no effect at all on the unconditioned reflex response. In marked contrast, conditioned responses were easily trained in the eye contralateral to the cerebellar lesion. We suggest that at least part of the essential neuronal plasticity that codes the learned response may be localized to the cerebellum.

Animals↗
PubMed1978

Measurement of the bioavailability of iron, using the rat hemoglobin repletion test.

Variations in the AOAC official first action rat hemoglobin repletion test for iron were studied. These changes included (1) use of a simplified basal diet to eliminate ingredients which sometimes contribute too much iron; (2) increased fortification of the basal diet with vitamin E, pantothenic acid, and pyridoxine; (3) increased dietary copper; (4) variations in the carbohydrate source in the basal diet; (5) changes in the length of the depletion and repletion periods; and (6) comparison of prophylactic and curative procedures. The changes yielded results comparable to those obtained with the present official method. Further study may reveal that the depletion period can be shortened or eliminated. To fully meet the rat's vitamin requirements, increased levels of vitamin E, pantothenic acid, and pyridoxine are recommended. It is further recommended that the present method remain in official first action status, and that study be continued.

Animals↗
PubMed1975

Estimation of the bioavailability of iron.

Eight laboratories conducted a test for the estimation of the bioavailability of iron from 4 sources, using depleted male albino rats. Ferrous sulfate was used as the reference standard. Ferric orthophosphate was found to have a relative biological value of 11 (range 6-22), an old sample of hydrogen-reduced iron 27 (range 15-41), and ferric citrate 96 (range 75-125). Good results were obtained with a simplified basal diet prepared without ingredients that had previously contributed variable quantities of iron. There was no apparent advantage in using the change in hemoglobin during the repletion period instead of the final homoglobin value as the criterion of response to iron supplements. Several statistical treatments of the data yielded similar conclusions regarding relative biological values of the iron sources.

Animals↗