T.P.S. Powell

An experimental study of the termination of the lateral geniculo–cortical pathway in the cat and monkey

The thalamic projection to the visual cortex has been studied in the cat and monkey by experimental light and electron microscopic techniques. After large lesions of the lateral geniculate nucleus degeneration is confined to the ipsilateral hemisphere. In the cat it is found in areas 17, 18 and 19 and in the lateral suprasylvian area, terminal degeneration occurring predominantly in layer IV, with less in layers I, III and V ; fibre degeneration crossing layers VI and V towards layer IV is coarser in area 18 than elsewhere. Some fine horizontal degenerating fibres are seen in layer I. In the monkey terminal degeneration is restricted to area 17; again degenerating fibres ascend to layer IV where there is dense fragmentation, but in contrast to the cat there is also a second, less dense, but distinct, band in layer Illb. A little fine, horizontal fibre degeneration is present in layer I and there is slight terminal degeneration in this site and in layer V. Electron microscopy shows that degenerating terminals are recognizable in the visual cortex at several stages according to survival period, but that most stages can exist simultaneously in any one site, and that all are associated with asymmetrical membrane thickenings. Mapping of electron microscopic sections confirms the laminar pattern seen with the light microscope. In area 17 of the cat and monkey and in area 19 of the cat over 80% of degenerating terminals end on dendritic spines, the rest making synaptic contact mainly with dendritic shafts, and very few with the soma of stellate cells, but in area 18 some 10 % are related to stellate cell bodies. In layer IV of all areas degenerating terminals tend to occur in clusters which are separated by approximately 100 μm. Where degenerating thalamic afferents end on cell somata or varicose dendrites almost all are identifiable as derived from stellate cells. Although it is difficult to identify positively the parent dendrites bearing the spines which receive the majority of the thalamo-cortical afferents, it is suggested that some, at least, of them may also originate from stellate cells.

An electron microscopic study of the mode of termination of cortico-thalamic fibres within the sensory relay nuclei of the thalamus

The existence of corticofugal fibres passing from the main sensory areas of the cerebral cortex to the thalamic relay nuclei has been confirmed by an electron microscopic study of the ventropo sterior, and medial and lateral geniculate nuclei 3 and 4 days after lesions in the appropriate cortical area. The degenerating cortico-thalamic fibres belong to the smallest group of myelinated axons found in the nuclei. Four days after a cortical lesion many degenerating axon terminals are found in all three nuclei, often in small clusters. These usually terminate outside the synapticglomeruli of then ucleus on stem dendrites and on the long parent profiles of the pale axon terminals of the glomeruli. In many cases, these dendrites and long parent processes enter a glomerulus close to or at some distance from the degenerating synapse. In a few cases, a degenerating terminal ends in closer relation to a glomerulus, usually on one of the more peripherally placed pale axon terminals. These findings indicate that the terminals of cortico-thalamic fibres belong to the small dark group of axon terminals described in the normal nuclei, but the persistence of many small dark terminals after total hemidecortication suggests that others have a subcortical origin. Four days after a cortical lesion, degeneration of the cortico-thalamic terminals is at a very advanced stage, whereas at a survival period of three days, only a few terminals show unequivocal degeneration. The degenerative change thus appears to be sudden and rapid.

The projection of the lateral geniculate nucleus upon the cortex in the cat

The retrograde cell degeneration in the lateral geniculate nucleus of the cat has been studied after lesions of the visual and adjoining areas of the cortex. Following lesions which are limited to area 17, the medium and small cells of the main laminae of the nucleus degenerate; damage restricted to area 18 does not result in any localized, severe degeneration, but combined destruction of areas 17 and 18 causes all the cells—large, medium and small—of the main laminae and the central interlaminar nucleus to degenerate. Cellular change in the medial interlaminar nucleus is only found after involvement of area 19. When the cortex of the middle suprasylvian gyrus is removed in addition to these areas the degeneration in the lateral geniculate nucleus is much more severe, and there is loss of the laminar pattern due to severe gliosis in the central interlaminar nucleus. There is a well-defined topical organization in the geniculo-cortical projection, and in the antero-posterior dimension it is the same to all areas of the visual cortex, anterior parts of the nucleus projecting anteriorly and posterior parts posteriorly. Medial parts of the main laminae are related to the lateral part of area 17 and to the medial part of area 18, and lateral parts of the laminae project to the medial part of area 17 and to the lateral part of area 18. After partial lesions which involve both areas 17 and 18 the cellular degeneration affects the laminae differentially along their antero-posterior extent, that in lamina A being the most anterior and that in lamina B the most posterior; in sagittal sections such a band, or column, of degeneration passes from antero-superior to postero-inferior at right angles to the plane of the laminae.

Retrograde changes in cholinergic neurons in the basal forebrain of the rat following cortical damage.

The effects of unilateral cortical damage on immunohistochemically identified cholinergic neurons of the basal nucleus have been examined in the rat. In the first 2 weeks after operation, the cells were swollen and their nuclei became eccentric, these changes being closely similar to those seen in the cholinergic oculomotor nuclei of the same animals following removal of the extraocular muscles. During the third week these acute changes were replaced by shrinkage of the cholinergic cell bodies and their dendrites. At longer survival times the appearance of the neurons did not alter, and all the cholinergic cells persisted in their shrunken form after 120 days, the longest survival time examined.

The cholinergic nuclei of the basal forebrain of the rat: normal structure, development and experimentally induced degeneration

The normal morphology and distribution of the cholinergic neurones of the basal forebrain of the rat have been studied qualitatively and quantitatively after staining immunohistochemically with a monoclonal antibody to choline acetyl transferase (ChAT). This was done in order to provide an adequate control for the changes found in these cells on both sides of the brain in the experimental investigation of the reaction of the cells to damage of their axons. The cholinergic cells form a more or less continuous anteroposterior band, but they can be subdivided into distinct nuclear groups on the basis of the size and form of the cell bodies and dendrites, their position and arrangement. these nuclei conform closely to previous descriptions of Nissl-stained material: the medial septal nucleus, the vertical and horizontal nuclei of the diagonal band and the basal nucleus. Quantitative measurements of the cross-sectional areas of the cells in the different nuclei confirmed the conclusions drawn from the qualitative examination. Measurements of the ChAT cells at different ages showed that in all nuclei they are significantly larger in size in infancy than in the adult, and they shrink to the mature size by 46 days. The cells in the various cholinergic nuclei show distinctly different reactions to damage of their terminal axonal fields. After removal of a large part of the neocortex by removal of the overlying pia-arachnoid mater the cells in the basal nucleus in the operated hemisphere underwent retrograde cellular degeneration, being swollen and paler-staining up to 14 days, and thereafter shrinking by 20-30% (as compared with those in the brains of age- and sex-matched littermate controls). The degree of shrinkage was appreciably greater when the animals were operated upon at the neonate stage. No cell loss was found, qualitatively or quantitatively, in the basal nucleus. After removal of the hippocampus there is marked loss of cholinergic neurones in the medial septal nucleus and in the vertical nucleus of the diagonal band, and with severe shrinkage of the remaining cells. Removal of the olfactory bulb results in only slight shrinkage of the cells, and no cell loss, in the horizontal nucleus of the diagonal band.(ABSTRACT TRUNCATED AT 400 WORDS)

The organization of the connections between the cortex and the claustrum in the monkey.

The distribution of labelled cells and of extracellular granules in the claustrum has been studied after injections of horseradish peroxidase in several areas of the neocortex. The frontal and parietal lobes are related to the anterior and posterior halves respectively of the claustrum, and the occipital and temporal cortex to the posterior and inferior margins. Parts of the claustrum related to areas of the cortex in the frontal lobe overlap considerably in the antero-posterior dimension with parts related to widely separated but interconnected areas of the parieto-temporal cortex. Areas of cortex within one lobe which are interconnected are related to parts of the claustrum which overlap in the dorsoventral dimension.

Electron Microscopy of Synaptic Glomeruli in the Thalamic Relay Nuclei of the Cat

The normal fine structure of the ventroposterior, and medial and lateral geniculate nuclei of the thalamus has been examined in the cat, particular attention being paid to localized aggregations of pre- and postsynaptic profiles which have been termed ‘glomeruli’, and which are common to these and certain other thalamic nuclei. The ventroposterior and medial geniculate nuclei show many similarities. Their glial-ensheathed glomeruli have one (or occasionally two) central dendrites which are usually bulbous side branches of main stem dendrites arising from neurons in the nuclei. These side branches commonly contain bundles, rings and whorls of neurofilaments. Two types of axon terminal complete the glomerulus: every glomerulus contains one (or at most two) large dark terminals; these have a heavy concentration of synaptic vesicles and a dense background cytoplasm and are derived from axons of medium diameter. They make asymmetrical synaptic contacts with the central dendrite and (axo-axonically) with the second type of terminal. This second type is a pale terminal with a clear cytoplasm and contains fewer synaptic vesicles than the large dark type; several pale terminals occur in a single glomerulus and they make short symmetrical synaptic contacts with the central dendrite only. Both types of axon terminal are also joined to the central dendrite by multiple adhesion plaques. The pale axon terminals are bulbous enlargements of long beaded processes; these come off very large unmyelinated profiles which resemble axon hillocks and may, therefore, be recurrent collaterals of thalamo-cortical relay cells or axons of interneurons. The commonest type of axon terminal outside the glomeruli is a small dark type which makes asymmetrical synaptic contacts with dendrites and the long beaded parent processes of the pale axon terminals, each of which may enter glomeruli close to or at some distance from this synapse. Dendrites beyond the point at which they enter glomeruli may be completely surrounded by small dark terminals.

Selective degeneration of interneurons in the motor cortex of infant monkeys following controlled hypoxia: a possible cause of epilepsy

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.

Mapping by Microstimulation of Overlapping Projections from Area 4 to Motor Units of the Baboon's Hand

It is known that the preferential accessibility of motor units of the baboon’s hand to cortical stimulation depends on the existence of colonies of pyramidal neurons which project monosynaptically to the appropriate spinal motoneurons. A complete description of the architecture of such a colony would include the size, shape and localization of its cortical territory; the maximum quantity of monosynaptic depolarization it can evoke in its target motoneuron; local variations of texture (density of output cells) within the territory; and extent of overlap, if any, between its territory and the territories occupied by other colonies. Systematic intracortical exploration with a stimulating microcathode excites spheres of tissue whose radii, at different current strengths, can be estimated within acceptable limits of accuracy. Such spheres are small in relation to the size of a colony, and can contain no more than a fraction of its pyramidal cells. Piecing these spheres together reveals the size, shape and texture of colonies and of the aggregations of colonies projecting to the motoneuron pools of particular hand muscles (1st dorsal interosseus, flexor and adductor pollicis brevis, extensor digitorum communis).They are localized in that part of area 4 that lies buried in the rostral wall of the central sulcus. Such aggregations occupy cortical territories measuring as much as 6.0 mm × 5.5 mm. Microstimulation provides critical evidence that they overlap. The words ‘discrete’ and ‘mosaic’ therefore have no place in the description of the fine-grained structure of cortico-motoneuronal output in the baboon. To discharge every cell in a colony simultaneously it is necessary to employ surface stimulation. Maximum output can be measured only by intracellular recording from the target motoneuron.

Retrograde cell degeneration in the basal nucleus in monkey and man

Retrograde cellular degeneration has been found in the basal nucleus of Meynert in macaque monkeys after large lesions of the neocortex, and in the human brain after either hemidecortication or leucotomy. These observations may be relevant to the interpretation of the cellular degeneration in the basal nucleus in Alzheimers disease.