Ultrastructural abnormality in Alzheimer neocortex.
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Biomedical subjects
Publications and source records attributed to J J Sloper.
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Measurements of cell area have been made in the lateral geniculate nuclei (LGNs) of 18 normal rhesus monkeys aged from 8 days to fully adult. There is much less variability between individual animals than had been thought from measurements of undeprived cells in experimental animals following visual deprivation. It is therefore possible to make reliable comparisons of cell size between different animals. There is no change in size of cells in the parvocellular laminae between 8 days of age and adulthood, although cells in the magnocellular laminae grow a little. In the primate, unlike the cat, the period of maximum sensitivity to visual deprivation does not correspond to a period of rapid cell growth in the LGN.
This study has examined the effects of monocular visual deprivation on cells in the lateral geniculate nucleus of the primate by comparing the sizes of cells in deprived and undeprived LGN laminae of experimental rhesus monkeys with those of cells in the corresponding laminae of normal animals. A number of conclusions may be drawn from this comparison: monocular visual deprivation has major effects on cells in the undeprived LGN laminae and these vary with age at closure; the initial effect of monocular closure from birth is to cause marked hypertrophy of undeprived parvocellular cells with little shrinkage of the deprived parvocellular cells, whereas late monocular closure (after 2 months of age) causes marked shrinkage of both undeprived and deprived parvocellular cells; following monocular closure at birth, the LGN abnormality continues to evolve until at least 3 months of age, with a marked parallel shrinkage affecting both deprived and undeprived parvocellular cells. The initial hypertrophy of the undeprived cells is reversed and the deprived cells become smaller than normal; cells in the monkey LGN are sensitive to visual deprivation until about 1 year of age, much later than previously thought. Visual experience, however, modifies this sensitivity so that the effects of monocular visual deprivation are both qualitatively and quantitatively different at different ages; there are important differences between the susceptibility of cells in the magnocellular and parvocellular laminae to visual deprivation; and actual shrinkage of cells to markedly below normal size occurs and the smaller size is not simply failure of growth.
Following monocular closure shortly after birth the deprived eye of 4 rhesus monkeys was reopened at different times. Following long-term recovery, cells in the undeprived laminae of the lateral geniculate nucleus of these animals were of normal size and those in the deprived laminae were markedly shrunken. Comparisons with animals monocularly deprived for similar periods indicate, however, that in 3 of these animals the undeprived parvocellular cells would have been markedly hypertrophied at the time of reopening the deprived eye, and in two of the animals, little shrinkage of the deprived parvocellular cells would have occurred by this time. Both undeprived and deprived parvocellular cells have therefore undergone marked shrinkage after the deprived eye had been reopened. The parallel shrinkage of deprived and undeprived parvocellular cells which occurs following closure at birth thus appears to be a consequence of the initial abnormalities produced by monocular closure rather than a direct result of the continuing lack of visual input to one eye.
Three infant monkeys were monocularly deprived from birth and reverse sutured at 3 weeks of age for a further period of 1, 2 or 5 weeks before perfusion. Cell areas were measured in the lateral geniculate nuclei and compared to those in normal monkeys and in monkeys following monocular closure. One week after reverse suture, cells in the initially deprived parvocellular laminae were 17% larger than normal and those in the initially undeprived laminae were 28% larger than normal. The initially undeprived parvocellular cells then shrank back to 14% larger than normal at 2 and 5 weeks while the initially deprived cells also remained hypertrophied. Following reverse suture at 3 weeks of age cells in parvocellular LGN laminae related to both eyes are simultaneously hypertrophied until at least 8 weeks of age and the LGN is therefore markedly abnormal even though the size difference between initially deprived and undeprived cells has been cancelled.
Following removal of the motor or sensorimotor cortex in infant monkeys the projections of the remaining motor or sensorimotor cortex have been studied after long-term survival to look for anomalous projections from these areas. The patterns of degeneration resulting from lesions of the remaining motor or sensorimotor cortex corresponded to those found in normal adult monkeys in the spinal cord, pontine nuclei, superior colliculus, parvocellular red nucleus, subthalamic nucleus and thalamus. Sparse degeneration was found in the magnocellular part of the contralateral red nucleus which has not been described in normal animals and there is also the possibility of an increase in the crossed corticostriate projection. Infant monkeys do not form anomalous projections comparable to those found in the rat following neonatal sensorimotor cortex lesions.
Comparisons of mean cell area in the lateral geniculate nucleus between normal and monocularly deprived Rhesus monkeys show that closure started in the first few days of life produces an initial hypertrophy of up to 25% affecting undeprived parvocellular cells. Hypertrophy is maximal at 4 weeks. Following this there is later shrinkage affecting both deprived and undeprived parvocellular cells so that ultimately undeprived parvocellular cells are about 10% smaller and deprived parvocellular cells about 35% smaller than corresponding cells in normal animals.
Measurements of mean cell area have been made in the lateral geniculate nuclei of 16 normal rhesus monkeys as a control for changes following visual deprivation. There is little variability between animals and no significant growth between 8 days of age and adulthood in the parvocellular laminae. The magnocellular laminae show more variability and some continuing growth after 8 days of age.
Comparisons of mean cell area in the lateral geniculate nucleus between normal and monocularly deprived rhesus monkeys show that late closure at between 3 months and a year of age produces up to 25% shrinkage of cells in the undeprived parvocellular laminae and up to 30% shrinkage in the deprived parvocellular laminae.
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Infant monkeys have been subjected to hypoxia with an arterial pO2 of 20-22 Torr for 30 min. Following perfusion 1-2 weeks later electron microscopy of the motor cortex shows a selective degeneration of axon terminals making symmetrical synapses and which probably arise from inhibitory GABAergic interneurons. It is suggested that this may be related to the development of epilepsy following hypoxia.
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Dendro-dendritic synapses have been observed infrequently in the deep layers of the motor cortex. The presynaptic dendrites are of a varicose type and themselves receive a considerable density of synapses both of the asymmetric and symmetrical type. The ultrastructure of the dendro-dendritic synapse itself shows the typical arrangement of presynaptic and postsynaptic membrane densities, often with presynaptic dense projections, and the membrane specialization is of the symmetrical type. There is the usual cleft containing electron-dense material between the presynaptic and postsynaptic profiles. The synaptic vesicles occur in a small cluster confined to a region close to the presynaptic membrane specialization; some of the vesicles are flattened and were shown by tilt analysis to be of the discoid type. Two examples were found of reciprocal dendro-dendritic synapses, both components being of the symmetrical type. A single axon terminal may make a synapse on to both dendrites involved in a dendro-dendritic synapse.
Gap junctions have been found infrequently between two dendrites or a dendrite and a cell soma in the deep layers of both the motor and somatic sensory cortices of the primate. At these junctions the outer leaflets of the plasma membranes of both profiles are intimately apposed with a gap of 2 nm between them which shows a structure of hexagonal subunits in tangential sections. These gap junctions occur mainly between the dendrites or dendrites and somata of large stellate cells but are also associated in some examples with a dendro-dendritic synapse and thus occur between large stellate dendrites and presynaptic dendrites; a desmosome may also occur in association with a gap junction and dendro-dendritic synapse. Gap junctions have been identified as sites of electrical transmission between cells in a number of sites and it is therefore suggested that some neurons in the sensori-motor cortex are electrotonically couples.