The site of termination of afferent fibres in the caudate nucleus

An electron microscopic study has been made of the axon terminal degeneration in the caudate nucleus in the cat after lesions in either the cerebral cortex, the thalamus, the cerebral cortex and the thalamus, the midbrain or within the caudate nucleus. Degenerating axon terminals can be recognized after a survival period of 4 days as dark, shrunken profiles with indistinct vesicles. After shorter survival periods the degenerating terminals contain swollen vesicles and have pale cytoplasm. After lesions in all the above sites there is degeneration of fine myelinated and nonmyelinated fibres. The degenerating terminals of all the afferent fibres to the caudate nucleus have asymmetrical membrane thickenings and end mainly on dendritic spines with a small proportion in contact with peripheral dendrites; after damage of the cerebral cortex or thalamus a few of the degenerating terminals also end upon main stem dendrites and cell bodies. The projection from the ipsilateral cerebral cortex is greater than that from the thalamus, which in turn is heavier than that from the contralateral cortex or midbrain. After lesions within the caudate nucleus degenerating terminals with symmetrical membrane thickenings are found in a region extending approximately 450 pm from the damaged part of the nucleus. These terminals make contact with nerve cell somata, main stem and peripheral dendrites and the initial segments of axons. After such a lesion of the caudate nucleus degenerating axon terminals with symmetrical membrane thickenings are also seen in the globus pallidus and the substantia nigra.

The synaptic organization of the caudate nucleus appears to be homogeneous with no specialized groupings of axon terminals and postsynaptic profiles. The nerve terminals in the caudate nucleus fall into two size groups, one about 1 fim in diameter and the other about 5 /itn diameter. The smaller size group, which comprises the majority of terminals, may be subdivided into three varieties on the basis of vesicle morphology and the type of membrane thickening. Most contain round, 45 nm diameter vesicles and are associated with asymmetrical membrane thickenings. Others contain 48 nm diameter, polymorphic vesicles, which become flat in material washed in cacodylate buffer, and are associated with symmetrical membrane thickenings. A few other terminals with symmetrical membrane thickenings contain flat 42 nm vesicles. The large terminals contain round 45 nm diameter vesicles and have asymmetrical membrane thickenings. Axon terminals with asymmetrical membrane thickenings are found most frequently in contact with dendritic spines, but also with dendritic shafts and cell somata. Terminals with symmetrical membrane thickenings contact dendritic shafts and cell somata, and occasionally dendritic spines with which a terminal with asymmetrical thickenings is also making contact. The two types of terminal with symmetrical contact regions also form synapses onto the initial segments of axons. It is probable that such contact regions are invariably associated with cisternal organs in the initial segments. Serial synapses are found occasionally.


The caudate nucleus of the cat appears to be homogeneous when examined with the light or electron microscope, except for a layer beneath the ependyma where there is a high concentration of glial cells and few neurons. In sections of brains stained with thionin the nerve cells in the caudate nucleus fall into three size groups: less than 8 μm, 9 to 18 μm, greater than 20 μm. Examination of material impregnated with the Golgi technique shows that there are six cell types (one small, four medium and one large), and these are distinguishable on the basis of the size of the cell somata and the appearance and arrangement of their dendrites. One type of medium cell with many dendritic spines forms over 95 % of the cell population. The large and one medium cell type are tentatively identified as the source of the efferent fibres of the nucleus. These efferent fibres and the axons of the remaining medium cell types have collateral branches. Three groups of possible afferent fibres have been identified, and these and the collateral branches of the intrinsic neurons form a dense plexus whose individual fibres cross dendrites rather than lie parallel to them. Six cell types may also be distinguished with the electron microscope, and four of these can be correlated directly with those seen in Golgi impregnated material. Several kinds of dendrites are present, the commonest having numerous spines. Fewer spines are present on other varieties of dendrite, and those dendrites which are varicose have no spines. Numerous fine, nonmyelinated axons are present.


1995 ◽  
Vol 12 (3) ◽  
pp. 425-441 ◽  
Author(s):  
Dom Miceli ◽  
Jacques Repérant ◽  
Jean-Paul Rio ◽  
Monique Medina

AbstractThe present study examined GABA immunoreactivity within the retinopetal nucleus isthmo-opticus (NIO) of the pigeon centrifugal visual system (CVS) using light- (immunohistofluorescence, peroxidase anti-peroxidase: PAP) and electron- (postembedding GABA immunogold) microscopic techniques. In some double-labeling experiments, the retrograde transport of the fluorescent dye rhodamine β−isothiocyanate (RITC) after its intraocular injection was combined with GABA immunohistofluorescence. GABA-immunoreactive (-ir) somata were demonstrated within the neuropilar zone of the NIO adjacent to the centrifugal cell laminae whereas the centrifugal neurons were always immunonegative. A quantitative ultrastructural analysis was performed which distinguished five categories of axon terminal profiles (P1–5) on the basis of various cytological criteria: type of synaptic contact (symmetrical or asymmetrical); shape, size, and density of synaptic vesicles as well as the immunolabeling (positive or negative), size of profile and appearance of hyaloplasm. Numerous GABA-ir afferents to centrifugal neurons via axon terminal types P2a, P2c, and P3 were observed which comprised 47.1% of the total input. Moreover, the data suggest that some of the P2a terminals, which make up 26.4% of the input, stem from the intrinsic GABA-ir interneurons, whereas the latter receive P1, P3, but also P2 terminal input, indicating that interneurons may contact other interneurons via type P2a axon terminals. The results also suggest that the GABA-ir P3 or the immunonegative P1b and P5 axon terminals are of extrinsic origin arising from cells in the optic tectum whereas the P2c and P4 axon terminals are associated with extra-tectal input to the NIO. The GABAergic innervation of centrifugal neurons within the NIO may be the basis for the demonstrated facilitatory effect of the centrifugal output upon ganglion cell responses. This is relevant to hypotheses regarding CVS involvement in attentional mechanisms through selective enhancement of retinal sensitivity depending on the location of meaningful or novel stimuli.


1968 ◽  
Vol 39 (3) ◽  
pp. 604-619 ◽  
Author(s):  
Alan Peters ◽  
Charmian C. Proskauer ◽  
Ita R. Kaiserman-Abramof

The axon of the pyramidal neuron in the cerebral cortex arises either directly from the perikaryon or as a branch from a basal dendrite. When it arises from the perikaryon, an axon hillock is present. The hillock is a region in which there is a transition between the cytological features of the perikaryon and those of the initial segment of the axon. Thus, in the hillock there is a diminution in the number of ribosomes and a beginning of the fasciculation of microtubules that characterize the initial segment. Not all of the microtubules entering the hillock from the perikaryon continue into the initial segment. Distally, the axon hillock ends where the dense undercoating of the plasma membrane of the initial segment commences. Dense material also appears in the extracellular space surrounding the initial segment. The initial segment of the pyramidal cell axon contains a cisternal organelle consisting of stacks of flattened cisternae alternating with plates of dense granular material. These cisternal organelles resemble the spine apparatuses that occur in the dendritic spines of this same neuron. Axo-axonal synapses are formed between the initial segment and surrounding axon terminals. The axon terminals contain clear synaptic vesicles and, at the synaptic junctions, both synaptic complexes and puncta adhaerentia are present.


The termination of fibres from the cerebral cortex and thalamus upon the dendritic spines of the medium spiny cell of the caudate nucleus has been studied with the Golgi method. Lesions were placed in the cerebral cortex, thalamus or cerebral cortex and thalamus of adult cats and kittens. After survival periods of between 6 and 52 weeks the animals were perfused with a mixture of formaldehyde and glutaraldehyde and the caudate nuclei impregnated by a Golgi technique. The distribution of spines along the dendrites of the medium spiny cell was determined in normal material by counting them over 20 /xm lengths of the dendrites, and was compared with their number and distribution after the various lesions. The density of spines on the dendrites varies with the distance from the cell body. The first 20 /xm length of dendrite is spine free, but thereafter the number increases to a peak between 60 and 80 /xm from the cell body after which the number per 20 /xm length decreases. The distribution pattern does not alter after any of the lesions, although the overall number of spines decreases. The decrease after lesions in the cerebral cortex or thalamus is the same, and after a combined lesion of thalamus and cortex is twice as great indicating that the fibres from both these regions end upon spines of the same cells. Statistical analysis shows that these results are significant.


An electron microscopic study has been made of the normal ventrolateral and centre-median nuclei of the thalamus of the monkey and, in experimental material, of the mode of termination in the nuclei of afferent fibres from the motor cortex, the globus pallidus and the deep cerebellar nuclei. There are striking similarities but also a few subtle differences in the ultrastructure of the centre-median and ventrolateral nuclei. Three classes of cell are present: a large multipolar cell with much cytoplasm filled with many organelles is probably the relay cell; a small fusiform cell with a thin rim of cytoplasm and light vacuolated mitochondria, which may contain discoid vesicles, gives rise to P profiles and axon initial segments; the third type is intermediate between the other two in size and other features. There are four types of vesicle-containing synaptic profiles. The most frequent are SR axon terminals, which are small, with spherical synaptic vesicles and are pre-synaptic at asymmetrical contacts with small and medium dendrites and their spines and P profiles; SR terminals are found mainly in the interglomerular neuropil. LR terminals, the largest synaptic profiles, are found in all glomeruli; they contain many round synaptic vesicles and form numerous asymmetrical synapses, being presynaptic to the main dendrite and all its spines and many of the P profiles in a glomerulus. P profiles are irregular pale processes, which occur in considerable numbers outside and within glomeruli (70% of intra-glomerular profiles) and contain pleomorphic synaptic vesicles which are discoid. They arise from tiny unmyelinated profiles and they may have synaptic interaction in several glomeruli. Larger processes, similar in character to proximal dendrites, but with discoid vesicles and synaptic features like those of smaller P profiles are also found, and may be in continuity with a cell soma. P profiles are post-synaptic to LR, SR and F axons, both pre- and postsynaptic to other P profiles and pre-synaptic to conventional dendrites; there are reciprocal synapses between pairs of P profiles. F axons, the least common profiles, are usually extra-glomerular and synapse with proximal dendrites and cell somata; they contain cylindrical synaptic vesicles and are pre-synaptic to P profiles and dendrites at symmetrical synapses. Cell somata in the centre-median nucleus possess spines, and in both nuclei dendrites have spines, both in glomeruli and the neuropil. Multivesicular bodies are frequently present in the parent dendrite subjacent to the spine. Spines in the neuropil are post-synaptic to SR and P profiles and, in the centre-median nucleus, also to F axons. Some spines appear to be post-synaptic only to F axons. At least half the extraglomerular spines are associated with two synapses, a dyadic arrangement with one synapse on the spine and one on the parent dendrite close to the base of the spine, while many dyads have only a single presynaptic profile. Some spines have a more complex synaptology including serial synapses and triads. In glomeruli, spines are always post-synaptic to the LR bouton and always dyadic as the LR terminal also contacts the dendritic shaft close to the base of the spine. Spines account for half the contacts between an LR terminal and the main dendrite in a glomerulus. Glomeruli are found in both nuclei and serial sections have shown the multiplicity of profiles and the complexity of synaptic organization within them. Each glomerulus contains one LR bouton, one main dendrite, and a large number of P profiles, with an occasional SR or F axon terminal at the periphery of the aggregation. The dendrites are of medium calibre, often with several spines, around which the other profiles are situated. An analysis is presented of the profiles and synaptic arrangements in thirty glomeruli from the centre-median and ventrolateral nuclei, with a reconstruction of one large glomerulus. The LR bouton makes numerous synaptic contacts with the main dendrite, half the contacts being upon spines, and a considerable number with P profiles. The latter also have many synapses, being approximately equally pre-synaptic to P profiles and the main dendrites. Various specific types of synaptic array are present within the glomeruli: serial synapses; sequential arrays, where the third profile of a serial synapse is again pre-synaptic; reciprocal synapses; triads which are similar to serial synapses but with an additional contact, profile 1 also being pre-synaptic to profile 3. The complexity of the glomerular synaptology is accentuated by the overlapping of several different types of synaptic array in a given glomerulus. Afferent fibres from the motor cortex and globus pallidus terminate in both nuclei as SR boutons, and in the ventrolateral nucleus the mode of termination of both groups of fibres is very similar. In the centre-median nucleus the terminals of fibres from the cortex have a higher proportion of multisynaptic contacts, are more frequently pre-synaptic to P profiles, and the dendrites upon which they end are less often in receipt of other synapses. The termination of fibres from the globus pallidus in the centre-median nucleus differs from terminals of fibres from the cortex and globus pallidus in the ventrolateral nucleus in being pre-synaptic to fewer P profiles. When the somatic sensory cortex was destroyed as well as the motor area degenerating axon terminals were present in the ventroposterior nucleus; their mode of termination was similar to those in the ventrolateral nucleus, but they were far greater in number. Axons from the cerebellar deep nuclei end in the ventrolateral nucleus as LR boutons within glomeruli. There was no evidence of degeneration in the centre-median nucleus after damage of the cerebellum.


An experimental electron microscope (e.m.) study has been made of the termination of the afferent connections to the primate sensori-motor cortex. Following large, stereotaxically placed thalamic lesions, degeneration in the motor and somatic sensory cortices was studied at survival periods of 4 and 5 days. Degenerating thalamocortical terminals had asymmetric membrane specializations. In the motor cortex 89.5% made synapses on to dendritic spines, 9% on to dendritic shafts and 1.5% on to cell somata; in the somatic sensory area 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; 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 thalamocortical axon terminals and the bundles of apical dendrites present at this level. Degeneration of commissural fibres was studied after removal of the contralateral sensori-motor cortex. Degenerating terminals had asymmetric membrane specializations. In the motor cortex 96% made synapses on to dendritic spines, 3% contacted dendritic shafts and one example made an axosomatic synapse; in area 3 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 V I; in the somatic sensory cortex 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; of those 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 nature and immediate postoperative course of experimental degeneration of axon terminals have been studied in the somatic sensory cortex. The first somatic sensory area was examined at intervals of 2 to 6 days following lesions in the thalamus, opposite cortex or ipsilateral second somatic sensory area. There is a characteristic sequence of degenerative changes which affects the terminals of each of the afferent fibre systems studied. This commences as a simple, though marked, increase in electron density of the axoplasm with no loss of synaptic vesicles and little alteration in the size or shape of the terminal. Following this, there is a progressive loss of vesicles and disruption of the mitochondria with shrinkage of the terminal and its compression, invasion and fragmentation by astroglial processes. There is evidence that many fragments are phagocytosed by the invading astroglia but a thin sliver always remains attached at the synaptic contact zone. Within the range of survival periods used, no changes affect the synaptic region nor the postsynaptic profile and if the latter is a dendritic spine, it is not detached from the parent dendrite. Changes in degenerating axons are similar, except that the largest thalamo-cortical fibres show a stage of neurofilamentous hyperplasia. In the cortex at a distance from the lesion only smaller astrocytic processes are involved in breaking down the degenerating products; close to a lesion, however, all astrocytic processes and perikarya become involved and many atypical glial cells which are difficult to classify as astrocytes or oligodendrocytes become visible; the vascular pericytes also display large heterogeneous dense bodies and other inclusions.


Layers I and II of the somatic sensory cortex are clearly distinguishable with the electron microscope because of characteristic differences in the number, type and orientation of neurons and dendritic and axonal ramifications. Layer I may be subdivided into: (i) a subpial astrocytic layer immediately deep to the basement membrane of the cerebral surface; (ii) a superficial quarter consisting of bundles of small myelinated axons and large numbers of small axon terminals which contain spherical vesicles and end in asymmetrical synaptic complexes mainly on large dendritic spines. Most of these terminals are derived from a dense feltwork of fine unmyelinated axons which are especially concentrated at the junction of the superficial and deep parts of layer I; (iii) a deeper three quarters with similar features to the above but with the additional characteristic of many obliquely orientated large dendrites which are the diverging branches of apical dendrites ascending from deeper layers. Small pyramidal neurons dominate layer II, but among them are a small number of non-pyramidal neurons whose beaded dendrites are covered with axon terminals. Large apical dendrites traverse this layer, and in addition to the typical asymmetrical synapse on dendritic spines, a few symmetrical types appear. These are derived from thin unmyelinated axons orientated horizontally within the layer, and the terminals contain many small flattened or pleomorphic synaptic vesicles.


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