A neurohistological study of the sensori-motor cortex

The electron microscope has been used to study the normal structure of the motor cortex (area 4 of Brodmann) and area 3b of the somatic sensory cortex in the monkey. The termination of the thalamo-cortical and commissural afferent fibres to both cortical areas, and the association connections to the motor cortex from the somatic sensory cortex and area 6 have been studied in experimental material. Because previous electron microscope studies have been mostly of sensory or parietal cortical areas the emphasis throughout this study has been on the structure and connections of the motor cortex and the somatic sensory cortex has been studied primarily to give a comparison with a different cortical area.
The general ultrastructural appearance of the motor cortex and area 3b of the somatic sensory cortex is remarkably similar. The neuropil of all layers consists predominantly of axon terminals and dendritic spines together with dendritic shafts, myelinated and unmyelinated axons. Layer I of both cortical areas contains a plexus of myelinated axons which was shown by light and electron microscopy to be markedly more dense in the motor cortex than in the somatic sensory cortex, although the diameters of the myelinated axons in both areas were similar. In layers II and III there are numerous neurons between which run vertical lengths of apical dendrite and these layers contain relatively few myelinated axons compared to the deeper layers of the cortex. Layer IV, in both the motor and somatic sensory cortices, contains conspicuous stellate cell somata which receive large numbers of synapses and in the motor cortex these extend both above and below the narrow layer IV which is conventionally described. There is a considerable increase in the number of myelinated axons at and below this level in the cortex and in sections of layer IV cut parallel to the pial surface the apical dendrites which run vertically through layer IV may be seen to occur in bundles of six to twelve dendrites. Layer V contains the prominent Betz cells and similar, but smaller, large pyramidal cells are present in layer V of the somatic sensory cortex. Both layers V and VI contain predominantly pyramidal and fusiform cells and these layers in the motor cortex are considerably thicker than in the somatic 'sensory cortex, this difference accounting for most of the difference in overall thickness between the two cortical areas.
Pyramidal and stellate cell types have previously been recognised in the neocortex with the electron microscope. A detailed study has been made here of the neuronal somata in the sensori-motor cortex. Pyramidal cells in the motor cortex are very similar to those described previously in sensory and parietal cortical areas. The largest pyramidal cells in area 4, the Betz cells of layer V, are up to 50 μ in transverse diameter. Although basically resembling smaller pyramidal cells, the nucleus of a Betz cell often has a complex indentation and is smaller in relation to the overall size of the cell soma than, is that of a smaller, pyramid and the cytoplasm of Betz cells contains discrete clumps of endoplasmic reticulum. As with other pyramidal cells, the synapses on to Betz cell somata are all of the symmetrical type. Previous descriptions of stellate cells have been of cells receiving a high density of axosomatic synapses of both the asymmetric and symmetrical type. Cells like this are found both in the motor and somatic sensory cortices and have been termed here large stellate cells. In addition to their high density of axosomatic synapses, they have abundant cytoplasm full of organelles and usually containing stacks of endoplasmic reticulum. Their dendrites similarly receive a high density of asymmetric and symmetrical synapses and contain prominent organelles and have a moderately varicose shape. Large stellate cells occur predominantly in layer IV in area 3b but in the motor cortex they are also found commonly in the lower part of layer III and the upper part of layer V.
A third class of neuron has been described in both the motor and somatic sensory cortices and cells of this type have been termed small stellate cells. These receive a low density of axosomatic synapses, but some of these are of the asymmetric type, and they have sparse cytoplasm with few organelles. They have a small rounded or fusiform soma, they frequently have a dark nucleus, they have no apical dendrite and their axon initial segments are thin and may be directed towards the cortical surface. Most of the rounded small stellate cells occur in layer II whereas those with fusiform somata occur more in the deeper layers of the cortex.
A quantitative study was made of the cells in a strip of the same width running through the full depth of the cortex in both cortical areas. The absolute numbers of cells in the strips of the motor and somatic sensory cortices were very similar as were the proportions of each type of neuron, 72% being pyramidal in each area with 21% being small stellate and 7% being large stellate in the motor cortex and 23% small stellate and 5% large stellate in area 3b. The quantitative study also provided evidence that large and small stellate cells form two distinct populations rather than being a continuum.
The axon initial segments of cells of all three types have a membrane undercoating and bundles of neurotubules. Those of pyramidal cells are directed towards the white matter whereas those of large and small stellate cells often run obliquely or towards the cortical surface and may be curved. Pyramidal initial segments may have spines which receive symmetrical synapses as do the shafts of the initial segments. The full length of the initial segment was studied for fourteen pyramidal and two large stellate cells. All gave rise to myelinated axons although two pyramidal cells had lengths of unmyelinated axon between the initial segment and myelinated axon. One of these lengths of unmyelinated axon made an asymmetric synapse on to a dendrite just after losing its initial segment features. Quantitative analysis of these complete initial segments showed that, whereas the diameter of the initial segment and the axon it gave rise to were approximately proportional to the size of the parent cell soma over a considerable range of cell diameters, the length of the initial segment appeared to be unrelated to either its diameter or the size of its parent soma but varied between 30 μ and 55 μ apparently at random. Synapses were evenly distributed along the full length of the complete pyramidal initial segments, but the density of synapses on the initial segments of supragranular pyramids was about three times that on those of infragranular pyramids and cisternal organs were similarly more frequent in the initial segments of supragranular pyramids.
Both cisternal organs in axon initial segments and subsurface cisternae in cell somata and dendrites have been found to be related to axon terminals making symmetrical synapses on to these same structures. The cisternal organ or the dense plate of the subsurface cistern is closely apposed to the overlying plasma membrane opposite the non-synaptic part of the symmetrical axon terminal and the membranes of both the terminal and initial segment, soma or dendrite may show some degree of specialisation at this site, The dense plates of both cisternal organs and subsurface cisternae are specifically stained by ethanolic phosphotungstic acid, thus resembling the spine apparatus, and it is suggested that the role of all three structures is similar. Ethanolic phosphotungstic acid also stains the membrane undercoating of axon initial segments and nodes of Ranvier, cilia, nucleoli and degenerating axons and axon terminals as well as the synaptic membrane complexes.
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 pre- and postsynaptic membrane densities, often with presynaptic dense projections, and the membrane specialisation is of the symmetrical type. There is the usual cleft containing electron-dense material between the pre- and postsynaptic profiles. The synaptic vesicles occur in a small cluster confined to a region close to the presynaptic membrane specialisation; 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, and 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. 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 coupled.
Study of the process of degeneration in the sensori-motor cortex has shown the degeneration to be mainly of the dark type with shrinkage and engulfment by glia. Micropinocytosis of degeneration has been observed and both glial profiles and dendrites, spines and neuronal somata have been observed to be taking up degeneration by this process. Similar micropinocytosis has also been observed in which a normal neuronal profile is apparently engulfing a small portion of another normal neuronal profile. Exposed postsynaptic membrane specialisations have been seen following lesions and are frequently associated with a subsurface cistern in an apposed profile.
Following large, stereotaxically placed thalamic lesions the degeneration in the motor and somatic sensory cortices was studied with the electron microscope at survival periods of 4 and 5 days. Degenerating thalamo-cortical terminals had asymmetric membrane specialisations. In the motor cortex 89.5% made synapses on to dendritic spines, 9% on to dendritic shafts and 1.5% on to cell somata and in area 3b 89% made synapses on to spines, 11% on to dendritic shafts and one example contacted a cell soma and a spine. A considerable number of the spines receiving synapses from degenerating thalamo-cortical terminals were traced to their parent dendrites and these were of the pyramidal type whereas the dendritic shafts and cell somata contacted by degenerating thalamo-cortical terminals were mostly of the large stellate type. Most of the thalamo-cortical degeneration in both cortical areas occurred in a dense band in the upper two-thirds of layer IV and the lower half of layer III but a number of degenerating terminals were found deep to this and in the motor cortex a second, less dense band of degeneration was present in the lower part of layer V and top of layer VI. Degenerating thalamo-cortical terminals making synapses on to dendritic shafts and cell somata were scattered through the deep half of the cortex and not concentrated in the dense band of degeneration and so formed a greater proportion of the degeneration in the deep layers, particularly in the motor cortex. Sections cut parallel to the pial surface in layer IV of the motor cortex showed a statistically significant association between the degenerating thalamo-cortical axon terminals and the bundles of apical dendrites present at this level.
Degeneration of commissural fibres was studied at 4, 5 and 6 days after removal of the contralateral sensori-motor cortex. Degenerating terminals had asymmetric membrane specialisations. In the motor cortex 96% made synapses on to dendritic spines, 3% contacted dendritic shafts and one example made an axosomatic synapse; in area 3b, 97% made synapses on to dendritic spines and 3% contacted dendritic shafts. A number of the spines receiving synapses from degenerating commissural axon terminals were traced to their parent dendrites and these were of the pyramidal type. The cell soma and the majority of the dendritic shafts receiving synapses from commissural terminals were of the large stellate type although some of the dendritic shafts were probably those of small stellate cells. In the motor cortex degenerating commissural axon terminals were found in all cortical layers but were relatively more dense in layer I, the upper part of layer III, the upper part of layer V and the lowest part -of layer V with layer VI; in area 3b most degenerating commissural terminals were found in the superficial half of the cortex.
Following lesions of the primary somatic sensory cortex (SI) or of area 6 of the premotor cortex degenerating terminals making asymmetric synapses were found in the motor cortex. Of the terminals of association fibres from SI, 82% made synapses on to dendritic spines and 18% on to dendritic shafts and of those of fibres from area 6, 76% made synapses on to dendritic spines and 24% on to dendritic shafts. For both these association fibre connections a proportion of the dendritic shafts contacted were clearly identifiable as those of large stellate cells. Terminals of both association connections occurred in all cortical layers with no obvious concentrations at any particular depth.
The normal and experimental results have been discussed together and in relation to the physiology of the motor cortex. On the basis of these results a simple model of cortical circuitry has been proposed and its properties have been explored to see what aspects of normal and abnormal cortical function can be simulated.

Advisor: Powell, T