Martin L. Feldman

The projection of the lateral geniculate nucleus to area 17 of the rat cerebral cortex. I. General description

SummaryLesions were made in the lateral geniculate nucleus of the rat and the consequent degeneration in area 17 of the cerebral cortex was studied by light and electron microscopy. These lesions produced prominent degeneration of axon terminals in layer IV extending into layer III and a much lesser amount in layers I and VI. The darkened degenerating axon terminals forming asymmetric synaptic junctions and were frequently surrounded by hypertrophied astrocytic processes. These terminals appeared to be disposed randomly, forming no discernible patterns. In layer IV 83% of the synapsing, degenerating terminals formed junctions with dendritic spines, 15% with dendritic shafts, and 2% with neuronal perikarya. The dendritic shafts and neuronal perikarya appeared to belong to spine-free stellate cells. The dendrites giving rise to the spines receiving degenerating axon terminals could not be identified, for most of the spines appeared as isolated profiles that could not be traced back to their dendritic shafts. One example of a degenerating axon terminal synapsing with an axon initial segment was encountered. Small, degenerating myelinated axons were prevalent in layers VI, V and IV, but were only infrequent in the supragranular layers. These results are compared with those obtained in other studies of thalamocortical projections.

Loss of dendritic spines in aging cerebral cortex

SummaryPrevious work has shown that the dendritic spines of pyramidal neurons of the cerebral cortex are sensitive to a wide variety of environmental and surgical manipulations. The present study shows that the normal aging process also affects these spines. The spines were studied with the light microscope in Golgi preparations from rats ranging in age from 3 to 29.5 months. Visible spines were counted on either 25 or 50 μ segments of the basal dendrites, apical dendrites, oblique branches, and terminal tufts of layer V pyramidal cells in area 17. A progressive loss of spines occurred at each of these loci. The smallest observed spine loss (24%) occurred on the dendrites of the terminal tuft, and the largest (40%) on the oblique branches. Age-related spine loss appears to affect all animals, and for animals of any one age the overall loss is similar. However, the cell-to-cell variability within an individual animal is pronounced, some cells with high spine densities being present at every age examined. As a general rule, there is a positive relationship between visible spine density along the apical dendrite as it traverses layer IV and the thickness of the dendrite. With advancing age, the relatively thick dendrites decrease in number so that the thinner dendrites make up an increasingly larger proportion of the total apical dendrite population. Questions that remain for the future include the genesis of the spine loss, its relation to other aging changes, and its functional significance for the neuron.

Hair cell counts in an age-graded series of rat cochleas.

Hair cells of Sprague-Dawley rats aged 2-33 months were counted in order to assess the magnitude, location and time course of cell degeneration. The mean number of hair cell places (hair cells plus phalangeal scars) was approximately 4700: 960 inner hair cell places and 3470 outer hair cell places. These numbers do not vary systematically with age. Hair cell degeneration was observed in all animals. At 31-33 months of age, animals had inner hair cell losses ranging from 1.6 to 4.2% and outer hair cell losses ranging from 2.1 to 23.3%. The loss of hair cells was greatest in the upper apex, where the 31-33-month-old animals had 3.1-9.2% inner hair cell losses and 7.4-46.8% outer hair cell losses. Outer hair cell losses were also large in the basal end, where inner hair cell losses were small. In the older animals, hair cell losses were consistently most prominent in the third row of outer hair cells. Following examination of the hair cell population, the ganglion cells in the apical region were evaluated in a number of cochleas. No significant correlation was found between the magnitude of inner hair cell and ganglion cell losses.

The projection of the lateral geniculate nucleus to area 17 of the rat cerebral cortex. V. Degenerating axon terminals synapsing with Golgi impregnated neurons.

SummaryThe sites of termination of afferents from the lateral geniculate nucleus to layer IV and lower layer III in area 17 of the rat visual cortex have been determined by use of a combined degeneration—Golgi/EM technique. Degeneration of geniculocortical axon terminals was produced by making lesions in the lateral geniculate body. After the animals had been allowed to survive for two days, the ipsilateral visual cortex was removed and impregnated by the Golgi technique. Suitably impregnated neurons and their processes in layer IV and lower layer III were then gold-toned and deimpregnated for examination in the electron microscope. A search was made for synapses between degenerating axon terminals and the gold-labelled postsynaptic neurons.Geniculocortical synapses were found to involve: (1) the spines of basal dendrites, as well as those of proximal shafts and collaterals of apical dendrites of layer III pyramidal neurons; (2) the spines of the apical dendritic shafts and collaterals of layer V pyramidal neurons; (3) the perikaryon and dendritic spines of a sparsely-spined stellate cell; and (4) the perikaryon and dendrites of a smooth, bitufted stellate cell. In view of this variety of postsynaptic elements it is suggested that all parts of the perikarya and dendrites of neurons contained in layer IV and lower layer III which are capable of forming asymmetric synapses can be postsynaptic to the thalamic input.Finally, an analysis of the known neuronal interrelations within the rat visual cortex is presented.

The cortical plate and molecular layer of the late rat fetus

SummaryIn the cortical plate of the late prenatal rat fetus the neuroblasts can be considered to be of three types: mature neuroblasts which are prominent in the lower levels of the cortical plate and have some of the cytoplasmic and nuclear features of neurons, immature neuroblasts that have recently completed their migrations into the cortical plate, and migrating neuroblasts that are still in the process of moving to their definitive positions. Both of these latter types have darker cytoplasm than the mature neuroblasts. All of the neuroblasts have an apical process that extends directly towards the pial surface of the cortical plate and a basal process that is directed towards the intermediate zone of the developing hemisphere. In Golgi preparations some of these basal processes, particularly those of neuroblasts situated in the lower levels of the cortical plate, seem to have formed axons that pass through the intermediate zone to enter the developing white matter, in which they turn at right angles away from, and rarely toward, the midline. Other elements traversing the cortical plate are the ascending processes of spongioblasts that branch in the molecular layer and form expansions at the surface of the hemisphere. In the molecular layer the spongioblast terminal branches intertwine with the apical tufts of the ascending neuroblast processes and with thin processes that have the features of axons, to form a loose neuropil. In the cortical plate the spongioblast processes are usually closely and preferentially surrounded by the dark migrating neuroblasts and by the immature neuroblasts. Both of these latter may partially encompass spongioblast processes. Hence it is concluded that the spongioblast processes act as guides along which the migrating neuroblasts ascend through the cortical plate.

A study of barrels and pyramidal dendritic clusters in the cerebral cortex

Abstract Tangential sections from several areas of rat, cat, macaque, and human neocortex were examined in the light microscope. Two types of neuronal organization — barrels and dendritic clusters — are described. Barrel-shaped aggregations of stellate cell perikarya were examined in layer IV of the rat parietal cortex. The barrels have their axes oriented perpendicular to the pial surface and are apparent because the concentration of neurons in their walls is 1.5–2.0 times that in the barrel hollows. Although some ring-shaped neuronal aggregates were observed in the cortices in other species, they could not be found consistently. The dendritic clusters, in rat and cat, consist of groups of apical dendrites which radiate vertically from pyramidal cell perikarya. Their form varies with both cortical region and species. It is proposed that clusters are a general feature of mammalian neocortex. No readily apparent spatial relationship exists between barrels and clusters of the rat parietal cortex. The dimensions of the dendritic clusters are too small to equate individual clusters with neurophysiologically defined columns. The barrels, in those regions and species in which they have been described, are more likely candidates, although their very limited distribution suggests that, for most functional columns, other morphological correlates exist. It is suggested that, in general, the morphological element swhich primarily account for the columns are not perikaryal aggregates but patterns of extrinsic and intrinsic axon terminals.

Intranuclear rods and sheets in rat cochlear nucleus

SummaryIntranuclear inclusions in neurons of the rat cochlear nucleus are described. The inclusions are equivalent to the ‘rodlets’ of the classical microscopists and ultrastructurally are of two types: rodshaped and sheet-shaped. The rods and sheets of the cochlear nucleus increase in frequency with age and are extremely common in adult and aged animals. Each inclusion is an aggregate of fine filaments approximately 70 Å in diameter. A rod consists of a bundle of parallel filaments; a sheet consists of a stepwise array of pairs of filamentous layers.The literature on these inclusions is reviewed. They have now been seen in a wide enough variety of species and loci to be considered a common, rather than a remarkable, nuclear inclusion, although they are by no means universal. The evidence to date does not convincingly establish them as pathological entities.

BALLOONING OF MYELIN SHEATHS IN NORMALLY AGED MACAQUES

In aged animal brains, a variety of holes are formed in the neuropil. One type of hole, here designated as the myelin balloon, is an abnormality of the myelin sheath and is found in a number of diverse sites in the brain. Profiles of myelin balloons display rather smoothly rounded peripheral contours and typically range up to 10 μm in diameter, although exceptionally large examples may be twice this size. The balloons are bounded by lamellae of myelin, and to accommodate the contents of the balloon, the myelin sheath becomes split at the intraperiod line. Since the intraperiod line is formed by the apposition of the outer faces of the myelin-forming plasma membrane, the contents of the myelin balloons are, in effect, in continuity with the extracellular space, and it is suggested that the contents of the balloons are fluid, with the fluid exerting an outward pressure on the walls of the balloons to produce their spherical shapes. Myelin balloons are not only produced during aging but also occur in a number of genetic strains of mice and in a number of human disease states. They thus represent a non-specific, though distinctive and common, alteration of the myelin sheath and are a reflection of the fact that under a variety of conditions, including normal aging, oligodendrocytes are unable to maintain the integrity of their sheaths.

The effect of aging on the neuronal population within area 17 of adult rat cerebral cortex

The brains of Sprague-Dawley rats in various age groups from 3 to 33 months were fixed by perfusion with standard aldehyde solutions in order to determine the effects of aging on neuronal numbers. Several indices of cortical volume were then measured to determine whether neuronal packing densities were affected by age-related change in cortical volume. The lengths, heights and widths of individual hemispheres for 160 animals ranging in age from 1 day to 36 months were first determined, after which blocks of tissue were removed from area 17 of some of the brains. These blocks were osmicated, embedded in Araldite and sectioned at 1 micrometer to ascertain, in the vertical plane, the thickness of area 17 and, in the tangential plane, the packing density of the clusters of apical dendrites extending from layer V pyramidal neurons. Results indicate the overall dimensions of the cerebral hemispheres increased until 3 months of age, after which there was no further increase in size. Between 3 and 33 months of age there was no age-related change in either the thickness of area 17 or in the separation between dendritic clusters, indicating the volume of area 17 did not change after 3 months of age. Within individual age groups the amount of variation present is greater than that among age groups. Since the number of nucleus-containing neuronal profiles per unit area of layers II/III, IV, V, VIa and VIb was similar in two groups of three animals at 3 and 33 months of age and the diameters of neuronal nuclei were unchanged, there seems to be no significant change in the number of neurons contained in these layers of rat visual cortex between 3 and 33 months of age. It is therefore concluded that no neurons are lost from area 17 as the mature cerebral cortex ages.

The projection of the lateral geniculate nucleus to area 17 of the rat cerebral cortex. II. Terminations upon neuronal perikarya and dendritic shafts

SummaryThe forms of dendrites in layer IV receiving degenerating thalamocortical axon terminals directly on their shafts were examined in serial thin sections. Reconstructions showed these dendrites varied in thickness between 2.5 and 0.5 μm. They had essentially smooth contours and rarely showed evidence of protrusions or spines. They were further characterized by the presence of many synapses along their shafts. Only about one in 12 of these synapses was formed by degenerating thalamocortical axon terminals.These smooth dendrites emerged from neuronal perikarya that also received degenerating axon terminals which formed asymmetric synaptic junctions. Such cell bodies bore both symmetric and asymmetric synaptic junctions, and not all of the latter were caused to degenerate after a thalamic lesion. These postsynaptic neurons appeared to be of two kinds, ones with thin dendrites that often contained closely packed microtubules, and others with thicker dendrites that emerged from the poles of oval perikarya.