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G Lynch

Publications and source records attributed to G Lynch.

At least 469 records · Page 26Linked to original sources

Early onset and topographical distribution of hypertrophied astrocytes in hippocampus of aging rats: a quantitative study.

Our results indicate that the density of astrocytes exhibiting hypertrophy in the hippocampus increases dramatically and progressively with age, being significantly elevated even in mid-life (13 month) animals. However, the total population of astrocytic cells (hypertrophied and nonhypertrophied) in the quantified region is not significantly elevated. Further, the relative distributions of both hypertrophied and total glial cells remained remarkably constant at the three ages measured. Reactive hypertrophy of astrocytes therefore appears to occur "in place" and migration of astrocytes does not appear to be a major factor in the hippocampus during aging. Of particular note was the finding that astrocyte hypertrophy is far more prominent in synaptic terminal fields than in myelinated fibers of the same system.

Aging↗

A method for investigating the role of calcium in the shape change, aggregation and serotonin release of rat platelets.

1. Effects of the platelet secretagogues thrombin and Concanavalin A (Con A) on shape change and release have been studied under conditions where external Ca2+ and ADP have been controlled. 2. In the absence of detectable aggregation both Con A- and thrombin-induced release of serotonin are markedly dependent upon extracellular calcium. 3. Con A, unlike thrombin, does not produce aggregation in calcium-supplemented medium. 4. The above property of Con A suggests that, in combination with added creatine phosphate and creatine phosphokinase, this ligand will be of value in the analysis of calcium-dependent release in platelets.

Animals↗

Biochemical and physiological studies of long-term synaptic plasticity.

High frequency stimulation of fiber systems in the mammalian hippocampus produces a semipermanent increase in synaptic efficacy. This effect, long-term potentiation (LTP), has been of considerable interest as a potential substrate of memory due to its rapid onset and extreme persistence. Experiments are described that indicate that the locus of LTP is confined to the synaptic complex of the fibers stimulated; further, Ca2+ is shown to be essential for the initiation of LTP and may play a role in triggering this increase in synaptic efficiency. Data from biochemical analyses of LTP indicate that a 40,000 dalton synaptic membrane protein shows a highly reliable change in its endogenous phosphorylation following high frequency hippocampal stimulation. Phosphorylase kinase, a Ca2+ sensitive enzyme, is shown to specifically catalyse the phosphorylation of this 40,000 dalton protein. The data are discussed in terms of a working model in which the Ca2+ dependent phosphorylation of the 40,000 dalton protein produced by high frequency stimulation is a biochemical intermediate in the production of LTP.

Animals↗

Hippocampal aging and adrenocorticoids: quantitative correlations.

Altered neural-endocrine relations have been proposed as factors in mammalian aging. In the same rats from three age groups we quantified astrocyte reactivity in hippocampus, performed radioimmunoassays for plasma adrenocorticoids, and measured adrenal weight. These variables were correlated in individual animals and generally increased with age. The findings are consistent with recent hypotheses that endocrine levels are related to brain aging, either as cause or effect.

Adrenal Glands↗

Terminal proliferation and synaptogenesis following partial deafferentation: the reinnervation of the inner molecular layer of the dentate gyrus following removal of its commissural afferents.

The inner one-third of the dendritic region of the dentate gyrus granule cells in adult rats receives projections primarily from the commissural fibers of the contralateral hippocampus and the associational fibers of the ipsilateral hippocampus. At two to four days following the complete removal of the contralateral hippocampus, approximately 25% of the terminals in the inner molecular layer are observed degenerating. This provides an excellent model system to investigate possible terminal proliferation induced by deafferentation since (1) the experimental lesion is easily reproducible, (2) no retrograde reactions occur in the granule cells as a direct result of the lesion, (3) no shrinkage is detected in this region following commissural deafferentation, (4) the same dendritic region can be relocated precisely in each animal, and (5) the synaptic counts are highly consistent between animals. Results from this study and from previous investigations demonstrate that the commissural projection is contained within a 0-80 mu zone directly above the granule cell layer; Complete photomontages of this zone were taken, but only the 40-80 mu zone was quantified for neuronal and glial changes in three normal, five 2- to 4-day, and five 50- to 75-day postlesion animals. The average synaptic count dropped to 64% of control values by 2 to 4 days, returned to 97% by 50- to 75 days postlesion, The number of terminals showing multiple synaptic contacts increased slightly in the long-term animals. Measurements of average terminal area showed no change between the short- and long-term survival groups. These results indicate that this dendritic region is reinnervated following partial deafferentation and that the reinnervation is due primarily to the formation of new terminals rather than the expansion of pre-existing terminals.

Afferent Pathways↗

Impaired synaptic potentiation processes in the hippocampus of aged, memory-deficient rats.

A series of neurophysiological experiments was performed on the Schaffercommissural system of the hippocampus of aged and young anesthetized Fischer rats. The aged Fisher rats were previously found to exhibit retention performance deficits. No obvious differences were found between aged and young animals in amplitude, latency, stimulation threshold, or wave forms of typical synaptic responses when these were elicited by control (0.3 Hz) stimulation pulses. Further, the temporal curves of facilitation during a paired-pulse series were not different in aged and young animals. However, aged and young synapses showed consistently different responses during repetitive stimulation. Synapses of aged animals were deficient in frequency potentiation processes during 12 Hz stimulation; and the aged animals exhibited a delayed rise of post-tetanic synaptic potentiation following a 5 sec, 100 Hz stimulation train. Moreover, aged synapses 'exhausted' more rapidly during continuous 4 Hz stimulation. Throughout these studies a biphasic pattern of potentiation was observed during repetitive stimulation (brief potentiation, depression, renewed potentiation). Aged animals were deficient primarily in development of the second phase of potentiation. This pattern suggests an age-related impairment of some secondary process of potentiation, leading to an increased tendency to synaptic depression during and after stimulation. The possibility that the impaired hippocampal synaptic plasticity may be related to reported deficient behavioral plasticity in the aged animals is considered.

Action Potentials↗

Long-term potentiation and depression of synaptic responses in the rat hippocampus: localization and frequency dependency.

1. The consequences of repetitive activation of excitatory synaptic inputs to the CA1 pyramidal cells of rat hippocampus have been studied using in vitro techniques. 2. Single stimulation trains of 100 pulses at rates of 5-100/sec resulted in potentiation of population spike amplitudes lasting the duration of a 5 min test period in thirty-four out of thirty-five cases. Trains of 100 pulses delivered at 1/sec resulted in depression of the stimulated pathway in ten out of twelve experiments. 3. Responses to test stimulation of other excitatory inputs to the same cell population were depressed following conditioning trains at frequencies in the range 1-100/sec. Depression was seen both in the population spike amplitude (reflecting synchronous cell discharge) as well as the extracellularly recorded population e.p.s.p., and appeared to be maximal at lower frequencies. 4. Trains of antidromic stimulation of the CA1 cell population produced subsequent decreases in synaptically evoked responses, indicating that repetitive firing of pyramidal neurones or interneurones do not cause potentiation, but may be involved in heterosynaptic depression. 5. The results suggest that potentiation and heterosynaptic depression arise from different mechanisms, and that potentiation is confined to the set of terminals activated by a conditioning train, whereas the depression is generalized to the whole neurone.

Animals↗

Anatomical and functional aspects of the septo-hippocampal projections.

The origins, distribution, and cellular targets of the septo-hippocampal projections are reviewed. It appears that the distribution of acetylcholinesterase-positive neurons in the medial septum and diagonal bands and those cells labelled after injections of horseradish peroxidase into the hippocampus coincide; however, the possibility of a non-acetylcholinesterase septal projection remains. Good agreement is found between the distribution of hippocampal acetylcholinesterase and the patterning of silver grains after injection of [3H]leucine into the medial septum. A major target of septal efferents to the hippocampus is the interneuron population; the possibility of septal mediation of intrahippocampal circuitry via this anatomical arrangement is discussed.

Acetylcholinesterase↗