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G S Lynch

Publications and source records attributed to G S Lynch.

At least 55 records · Page 3Linked to original sources
PubMed1993

Contractile properties of skinned muscle fibres from young and adult normal and dystrophic (mdx) mice.

1. Single muscle fibres were enzymatically isolated from the soleus and extensor digitorum longus (EDL) muscles of genetically dystrophic mdx and normal (C57BL/10) mice aged 3-6 or 17-23 weeks. 2. Fibres of both muscles were chemically skinned with the non-ionic detergent Triton X-100 (2% v/v). Ca(2+)- and Sr(2+)-activated contractile responses were recorded and comparisons were made between several contractile parameters of various fibre types of normal and dystrophic mice of similar age. 3. There were no significant differences in the following contractile parameters of skinned fibres of normal and mdx mice of the same age: sensitivity to activating Ca2+ (pCa50) or Sr2+ (pSr50) and differential sensitivity to the activating ions (pCa50-pSr50). However the maximum isometric tension (Po) and the frequency of myofibrillar force oscillations in EDL fast-twitch fibres of young mdx mice were significantly lower than those of soleus fast-twitch fibres of the same animals, or fast-twitch fibres (EDL or soleus) of normal mice. 4. Age-related differences were apparent in some contractile parameters of both normal and mdx mice. In particular the steepness of force-pCa and force-pSr curves increased with age in normal mice, yet decreased with age in fibres of mdx mice. 5. A fluorescent probe, ethidium bromide, which interchelates with DNA, was used with laser-scanning confocal microscopy to determine the distribution of myonuclei in fibres. Fibres isolated from either muscle type of normal animals displayed a characteristic peripheral spiral of myonuclei. Fibres from muscles of mdx mice displayed three major patterns of nuclear distribution; the normal peripheral spiral, long central strands of nuclei, and a mixture of these two patterns. 6. The contractile characteristics of mdx fibres were not markedly influenced by the nuclear distribution pattern in that there were no discernible differences in the major contractile parameters (the Hill coefficients nCa and nSr, which are associated with the steepness of the Ca2+ and Sr2+ activation curves, pCa50, pSr50, pCa50-pSr50) of skinned fibres possessing peripheral or central nuclei. However, except for nSr, these values were all lower in individual fibres which displayed similar proportions of central and peripheral nuclei. The presence of mixed nucleation and absence of fibres with embryonic contractile characteristics in mdx mice suggest that the dystrophin-negative fibres can repair locally occurring muscle damage.

Aging↗
PubMed1993

The effects of age and low-intensity endurance exercise on the contractile properties of single skinned fast- and slow-twitch skeletal muscle fibres.

Aged (25 month old) rats were subjected to a low-intensity exercise programme, consisting of 10-weeks endurance swimming. At the conclusion of training (at the age of 27 months), fresh single skinned muscle fibres were prepared from the extensor digitorum longus (EDL) and soleus (SOL) muscles of the hindlimb and activated in Ca(2+)- and Sr(2+)- buffered solutions to measure selected isometric contractile characteristics. The major fibre population of the SOL from trained aged animals demonstrated a higher threshold [Ca2+] and [Sr2+] for contraction and a reduced sensitivity to Sr2+. Few changes in contractile characteristics were observed in the EDL muscle fibres from exercised rats, except for fibre type specific changes in the steepness of the force-pCa and force-pSr relationship. The effect of ageing on the contractile characteristics of skinned muscle fibres was also investigated by comparing the data obtained from aged sedentary rats with that from adult (6-9 month old) sedentary rats. Ageing was shown not to have affected the single fibre contractile properties of the SOL, but did affect one of the two fibre populations of the EDL. This was illustrated by the higher sensitivity to Ca2+ in the aged muscle fibres with a concomitant decrease in the cooperative interactions within the thin filament during tension activation.

Aging↗
PubMed1991

Endurance exercise effects on the contractile properties of single, skinned skeletal muscle fibres of young rats.

Single fibres were isolated from the extensor digitorum longus (EDL) and the soleus (SOL) muscles of the hindlimb from young male Wistar rats which had undergone a 10-week programme of endurance swimming from the age of 2 weeks. Fibres were mechanically skinned and activated with Ca(2+)- and Sr(2+)-buffered solutions. Muscle fibres were classified by means of well-defined criteria concerning various aspects of their contractile behaviour. Most fibres could be allocated into specific groups; however, a significant proportion (13% of the sampled population) did not fit these rigid classifications but displayed contractile activation characteristics common to more than one fibre type. In these cases models which used a combination of both fast- and slow-twitch contractile and regulatory properties were used to characterise the activation behaviour of fibres. It is proposed that the exercise, initiated at a young age, induced changes in the contractile characteristics of the single fibres by modifying protein isoforms of the contractile apparatus.

Animals↗
PubMed1989

The neurobiology of learning and memory.

The study of memory is a great challenge, perhaps the greatest in biological sciences. Memory involves changes in a tiny fraction of an extremely large pool of elements, a conclusion that makes the task of finding those changes using current technologies formidable. What can be done about this roadblock to neurological investigations of learning? One response that has become particularly productive in recent years is to study learning or learning-like phenomena in relatively simple "model" systems. The idea is to extract basic principles from these models in which molecular and anatomical details can be studied and then to use these in analyzing learning in higher regions of the brain. In this article we discuss current progress and emerging concepts derived from the simple system approach using animal models.

Animals↗
PubMed1987

Spatial learning in the rat: impairment induced by the thiol-proteinase inhibitor, leupeptin, and an analysis of [3H]glutamate receptor binding in relation to learning.

Rats were given continuous intraventricular infusion of saline or the thiol-proteinase inhibitor leupeptin, via subcutaneously implanted osmotic minipumps, while being trained on a spatial learning water task using spaced trials. Leupeptin caused overnight forgetting during training, but performance eventually reached asymptote in both groups. A retention test conducted 48 h later to assess spatial memory revealed no significant group differences, but did cause, in saline-treated rats only, a disruption of subsequent retraining back to the correct spatial location. The groups showed no differences in Cl-dependent [3H]glutamate receptor binding to hippocampal or entorhinal cortex membranes subsequent to training. In a second experiment, normal rats trained on the same task also showed no differences in Cl-dependent [3H]glutamate binding relative to rats exposed to the water task but given random spatial position training and handled controls. The results are discussed in relation to the hypothesis of Lynch and Baudry (Science (1984) 224, 1057-1063) that a calcium-dependent thiol proteinase is involved in memory formation through its ability to modify glutamate receptor distribution and dendritic spine shape.

Animals↗
PubMed1983

Dentate granule cells in the rat hippocampal formation have the behavioral characteristics of theta neurons.

Recordings were made from the dentate gyrus granule cell layer of freely-moving rats. The neurons recorded from the layer were divisible into 3 classes using a combination of electrophysiological and behavioral criteria; the duration of the extracellularly recorded unfiltered action potential provided the most reliable means of differentiating between cell types. Class I and class II neurons always fired in short duration single action potentials, while class III neurons had broader waveforms and occasionally were observed to fire complex spikes. As the most obvious behavioral correlate of class I and class II neurons was movement of the rat, these cells correspond to the theta cells of Ranck. Class III neurons for which a behavioral correlate was observed had the characteristics of the place cells described by O'Keefe. The neurons of classes I and II comprised 89% (56 of 63) of the total population sampled in the granule cell layer. Most of these neurons (49 of 56) discharged at short latency in response to a stimulus delivered via the perforant pathway; in contrast, none of the class III neurons observed were activated in this way. Horseradish peroxidase or Fast Green dye ejection through glass microelectrodes recording class I cell activity in urethane-anesthetized animals revealed the electrode tip to be in the granule cell layer in 27 of 27 cases. Six single class I neurons were also antidromically activated by a stimulus from an electrode placed in the hippocampal mossy fibers, and collision testing was successful in all cases. It is concluded that the dentate granule cells are theta cells.

Animals↗
PubMed1982

The action of piracetam on the electrical activity of the hippocampal slice preparation: a field potential analysis.

The action of various doses of piracetam on the electrical responses of in vitro hippocampal slices from the rat was investigated. Piracetam increased dose dependently the amplitude of the population spike response of pyramidal neurons evoked by stimulation of the stratum radiatum. Piracetam began to affect the population spike at a dose of 100 microM and consistently increased it at a dose of 1 mM. The drug had a rapid onset of action and recovery was seen within a few minutes following its removal. The response of the pyramidal neurons to antidromic stimulation was not affected by piracetam at concentrations up to 50 mM. Also, neither the amplitude nor the slope of the dendritic response was changed by the drug.l Piracetam also did not affect either posttetanic or long-term potentiation of synaptic potentials. These findings suggest that the drug does not act through depolarization of the pyramidal cells or potentiation of the synaptic processes located on their dendrites. The action of piracetam on the feedforward- and feedback-mediated inhibition of pyramidal cells by basket cells was investigated in several series of experiments. At concentrations of 1 and 10 mM, piracetam did not change either of the two types of inhibitory mechanisms. Several hypothetical sites of action of piracetam are discussed.

Animals↗
PubMed1981

Micromolar calcium stimulates proteolysis and glutamate binding in rat brain synaptic membranes.

Incubation of cortical synaptic membranes with low concentrations of calcium resulted in a decrease in the amount of a high-molecular-weight doublet protein and an increase in the sodium-independent binding of glutamate. Both effects were blocked by the thiol protease inhibitor leupeptin. These results suggest that calcium-induced proteolysis of membrane components regulates the number of glutamate receptors in neuronal membranes.

Animals↗
PubMed1980

Reciprocal anatomical connections between anterior thalamus and cingulate--retrosplenial cortex in the rabbit.

Reciprocal anatomical connections between posterior limbic (i.e. cingulate-retrosplenial) cortex and anterior thalamus in the rabbit were investigated using horseradish peroxidase histochemistry. Results showed that the cells of origin for corticofugal fibers are contained only within deep cortical layers, while thalamofugal projections terminate only within superficial laminae. That is, only layer VI neurons of cingulate-retrosplenial cortex project to thalamic regions, while cortical layers I and IV are the primary targets of thalamic afferents.

Animals↗
PubMed1980

Reciprocal anatomical connections between hippocampus and subiculum in the rabbit evidence for subicular innervation of regio superior.

Anatomical connections between the dorsal hippocampus and subiculum were examined in the rabbit, using horseradish peroxidase (HRP) and autoradiographic methods. A previously undescribed pathway was found to project from the dorsal prosubicular-subicular region to dorsal hippocampal cell fields CA1 and CA2. Autoradiographic findings showed that subicular afferents travel via two routes. One pathway projected through the alveus and stratum oriens, with results suggesting collateral input to the basal dendritic pyramidal cell region. The other projection coursed through the stratum lacunosum-moleculare with apparent termination onto CA1 and CA2 apical dendrites. Regions of subiculum providing afferents to hippocampus were compared with subicular areas receiving efferent terminations from hippocampal CA1 and CA3 cell zones. Distribution of hippocampal-subicular terminations were regionally distinct from subicular retrograde cell fields in rostral areas of the subicular complex, extended over a much wider area of subiculum than was seen for retrograde-labeled cells, and was cytoarchitectonically organized. In total, findings indicated that a reciprocal anatomical relationship exists between dorsal hippocampus and subiculum in the rabbit.

Animals↗
PubMed1977

Ultrastructural evidence for bouton proliferation in the partially deafferented dentate gyrus of the adult rat.

A quantitative morphological study of the changes in the dentate gyrus molecular layer in response to the removal of perforant path afferents was made utilizing electron microscopic techniques. Alterations in 1. the population of remaining afferents, 2. glial cells, and 3. granule cell dendrites are reported. The major observation was an increase in intact bouton density in the region of denervation which began at 5 days post-lesion and continued through 11 days post-lesion, the longest post-lesion survival time studied.

Afferent Pathways↗
PubMed1977

Histochemical evidence of altered development of cholinergic fibers in the rat dentate gyrus following lesions. I. Time course after complete unilateral entorhinal lesion at various ages.

The entorhinal cortex of rats was removed at various times during development, and the reaction of the cholinergic septohippocampal input to the dentate gyrus was examined by use of acetylcholinesterase histochemistry. When the ipsilateral entorhinal cortex is completely removed, the outer 70-75% of the molecular layer of the dentate gyrus is almost completely denervated. After such a lesion at 5 to 33 days of age, the acetylcholinesterase staining initially intensified throughout the denervated area, indicating that the septohippocampal fibers branched or elongated. This reaction could be detected within one day after a lesion at 11 days of age and within three or five days after lesions at earlier or later times. Whereas the initial response of the septohippocampal fibers was independent of the age at which the lesion was made, their final localization depended on the developmental state of the animal. After lesions at the age of 5 or 11 days, the reactive septohippocampal fibers became restricted to the outer one-sixth to one-third of the molecular layer within two days after appearance of their initial reaction. A similar concentration of reactive fibers was demonstrable after lesions at 16, 18 or 21 days of age, but some reaction persisted in the middle third of the molecular layer. Finally, after lesions at 26 or 33 days of age the proliferating cholinergic fibers ultimately were uniformly distributed throughout the outer 60% of the molecular layer. These results suggest that septohippocampal fibers initially extend or sprout throughout the denervated area to replace the lost perforant path fibers. However, the reactive fiber population becomes restricted to the outer edge of the molecular layer if the entorhinal lesion is made before the period of cholinergic synaptogenesis and concentrates in this same zone if it is made while cholinergic synapses are forming. We suggest that either the proliferative reaction continues in the outer part of the molecular layer and subsides in other parts of the denervated area or septohippocampal fibers move outward through the molecular layer to assume a more superficial location. After entorhinal lesions at 16 days of age or later the pale-staining zone (containing fibers that originate in hippocampus regio inferior) immediately deep to the denervated area widened. If the lesion was made earlier, this zone never developed at most septotemporal levels of the dentate gyrus. These results are probably related to the extension of regio inferior fibers into the denervated area.

Acetylcholinesterase↗
PubMed1977

Histochemical evidence of altered development of cholinergic fibers in the rat dentate gyrus following lesions. II. Effects of partial entorhinal and simultaneous multiple lesions.

It has been concluded previously that the septohippocampal fibers which project to the rat dentate gyrus extend or branch in the denervated area of the molecular layer following a complete ipsilateral entorhinal lesion. The septohippocampal fibers thus appear to replace some of the perforant fibers which degenerate as a result of the lesion. The reactive fibers eventually become localized to a much smaller and more superficial area after lesions of immature rats than after lesions made in adulthood. To determine whether this difference in the response results from a selective reaction to loss of the lateral perforant path in the immature rat, various portions of the entorhinal cortex were removed at the age of 11 days, and the cholinergic septohippocampal fibers were visualized by acetylcholinesterase histochemistry. An alternative possibility, that the difference between immature and adult rats is attributable to an interaction with other reactive afferents, was tested by removing other sources of input (the contralateral entorhinal cortex, contralateral hippocampal formation or both) along with the ipsilateral entorhinal cortex at the age of 11 days and then demonstrating the septohippocampal fibers histochemically. Lesions of the lateral part of the ipsilateral entorhinal cortex (source of the lateral perforant path) at 11 days of age evoked a septohippocampal reaction along the outer edge of the molecular layer, where the lateral perforant path fibers normally terminate. This result matched that produced by a complete entorhinal lesion. Lesions of the medial entorhinal cortex evoked no obvious reaction. In contrast, the septohippocampal fibers in adult rats proliferated in the denervated area of the molecular layer after lesions of either part of the entorhinal cortex. Combining lesions of other sources of innervation to the dentate gyrus with an ipsilateral entorhinal lesion at 11 days of age did not alter the response of septohippocampal fibers, as determined histochemically. Neither did the septohippocampal fibers react to removal of commissural afferents alone. The response at any age was unaffected by prior or subsequent removal of the contralateral entorhinal cortex. These results indicate that in immature rats the septohippocampal fibers respond only to loss of the lateral perforant path, but these same fibers can later react to loss of any part of the perforant path. They are regarded as support for the hypothesis that the reactive septohippocampal fibers preferentially interact with dendritic growth cones. Our results do not support explanations based on a hypothetical attraction between septohippocampal and crossed perforant path fibers (which react in the same area) or on competition with commissural fibers (which reinnervate an adjacent area). We suggest further that proximity to the degenerating elements does not in itself determine the pattern of reinnervation after lesions of the central nervous system.

Acetylcholinesterase↗
PubMed1976

GDEE antagonism of iontophoretic amino acid excitations in the intact hippocampus and in the hippocampal slice preparation.

Glutamic acid diethylester (GDEE) reversibly antagonized excitations produced by glutamate and aspartate but not those produced by acetylcholine when applied iontophoretically to rat CA1 hippocampal neurons in penthrane (methoxyfluorane) anesthetized rats and to CA1 neurons in in vitro slice preparations. GDEE did not appear to differentiate between the excitations produced by glutamate aspartate and appeared to be a more potent antagonist than has previously been reported. CA1 cells were remarkably sensitive to acetylcholine; 5-50 nA being sufficient to produce marked amino acid-like excitations, which were unrelated to the pH of the acetylcholine. The nature of the responses to applied substances was virtually identical between the intact animal and the in vitro slice preparation. A description of the in vitro technique is given as an Appendix.

Acetylcholine↗