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Journal ArticleDOI

Enlarged synaptic vesicles as an early sign of secondary degeneration in the optic nerve terminals of the pigeon.

01 Mar 1970-Journal of Cell Science (The Company of Biologists Ltd)-Vol. 6, Iss: 2, pp 605-613
TL;DR: The conclusion seems warranted that the ballooning of synaptic vesicles is an early sign of terminal degeneration, it appears to precede vesicular disintegration.
Abstract: The terminal degeneration of retino-tectal fibres was studied electron microscopically in the pigeon Synaptic vesicles seem to undergo systematic changes which can best be observed in aldehyde-fixed material. Initially (i.e. within 12-24 h) the vesicles begin to swell. The enlargement is clearly visible after 4 days (40 % increase in diameter) and reaches a maximum at 14 days (100% increase). At the latter stage, the enlargement is almost invariably associated with the well known opacity of degenerating terminals. In contrast, normal control tissue contains nerve endings with only a few enlarged and no ballooning vesicles. The conclusion seems warranted that the ballooning of synaptic vesicles is an early sign of terminal degeneration, it appears to precede vesicular disintegration.
Citations
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Journal ArticleDOI
TL;DR: In each of the species examined evidence has been found for a direct projection from the retina to the suprachiasmatic nucleus, but to no other region of the hypothalamus, the possible role of this retinal projection in mediating a variety of light-induced neuroendocrine responses is discussed.
Abstract: Retino-hypothalamic connections have been studied autoradiographically in the rat, guinea pig, rabbit, cat and monkey following the intravitreal injection of 3H-leucine or 3H-proline, and electron microscopically following unilateral eye removal in the guinea pig and monkey. In each of the species examined evidence has been found for a direct projection from the retina to the suprachiasmatic nucleus, but to no other region of the hypothalamus. The projection to the suprachiasmatic nucleus is always bilateral (even in the albino guinea pig, in which all other components of the retinal projection are crossed) but from grain counts in our autoradiographs it appears that the input to the contralateral nucleus is about twice as heavy as that on the ipsilateral side. Most of the retinal fibers appear to terminate within the ventral part of the nucleus where they form asymmetric synapses either upon small dendritic branches or dendritic spines. The possible role of this retinal projection to the suprachiasmatic nucleus in mediating a variety of light-induced neuroendocrine responses is discussed.

467 citations

Journal ArticleDOI
TL;DR: 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.
Abstract: 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 IIIb. 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 $\mu $m. 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.

319 citations

Journal ArticleDOI
TL;DR: Degenerating axon terminals can be recognized after a survival period of 4 days as dark, shrunken profiles with indistinct vesicles, and after shorter survival periods the degenerating terminals contain swollen vesicle and have pale cytoplasm.
Abstract: 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 $\mu m$ from the damaged part of the nucleus. These terminals make contact with nerve cell somata, main stein 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.

314 citations

Journal ArticleDOI
TL;DR: The projections of dorsalRoot axons to the deeper laminae (IV, V, and VI) of the Macaque spinal cord were examined by the use of experimentally induced degeneration following dorsal rhizotomy or by injection of dorsal root ganglia with tritiated amino acids followed by light and electron mi‐croscopic autoradiography.
Abstract: This study examines the projection of dorsal root fibers to the upper dorsal horn of the monkey lumbar spinal cord utilizing degeneration and autoradiographic methods. The animals survived dorsal rhizotomy for periods varying from 18 hours to 28 days. Electron microscopy reveals the earliest degeneration to be neurofilamentous alteration of large synaptic profiles in lamina III and the inner zone of the substantia gelatinosa (IIi). This degeneration begins 18 hours after rhizotomy, reaches a peak at three days postoperatively and disappears by the end of the first week. Degenerating myelinated axons in the spinal gray matter, dorsal column white matter and Lissauer's tract first appear three days postoperatively. The second tye of degeneration of synapses occurs in lamina I and outer gelatinosa (IIo) and consists of electron lucent alteration of moderate size synapses, especially those having large granular vesicles (LGVs) and some neurofilamentous and dense degeneration. This synaptic degeneration in lamina I begins two days following rhizotomy and reaches a peak between five to seven days, declines markedly by ten days and is absent at four weeks survival. The third type of degeneration occurs in the substantia gelatinosa (laminae IIo and IIi) initially as an enlargement of synaptic vesicles at two days and then progresses to large numbers of electron dense small synapses, the peak of degeneration occurring at seven days and persisting as long as four weeks postoperatively. Some of the dense synapses can be seen to arise from small, nonmyelinated axons. These axons are first seen to be degenerating in the gelatinosal and marginal layers at four days survival and the first definite degeneration of nonmyelinated axons in Lissauer's tract is at seven days postoperatively. It is concluded that the largest axons projecting to this region of the dorsal horn degenerate most rapidly and that these axons are distributed to laminae III and IIi. Axons of intermediate diameter degenerate next and are distributed principally to laminae I and IIo. Fine diameter axons, probably nonmyelinated, degenerate more slowly and terminate principally in the substantia gelatinosa (IIi and IIo). There is some overlap in these projection domains, in that the principal projection to lamina III extends into the lower part of the gelatinosa and the projection to the marginal layer overlaps the outer gelatinosa. The axon terminals in gelatinosa of C fibers are sometimes postsynaptic in axoaxonal synapses as are several of the axon terminals of larger A fibers in lamina III. Most of the synapses of primary afferent origin in lamina I are not involved in axoaxonal synapses. It is likely that the terminations of many primary afferent fibers in laminae II and III are subject to presynaptic inhibition and those in lamina I are not. Some of the primary afferents in all three laminae synapse upon presynaptic dendrites and thus may influence transmitter release from these profiles. The LGV profiles are distributed in a manner similar to the distribution of substance P and it is suggested that the degenerating LGV profiles may contain substance P. Most of the LGV profiles and many of the round vesicle profiles do not appear to be derived from dorsal root, but most of the central synaptic profiles are of primary afferent origin. In no case was there evidence that flat vesicle synapses were derived from primary afferents. Following dorsal root ganglia injections with H3 leucine, light microscopic autoradiography at short postoperative survival times demonstrated heavy grain distribution over marginal and gelatinosal layers with somewhat less numbers of grains over lamina III. There were also many grains over the dorsal column white matter and Lissauer's tract. Electron microscopic autoradiography revealed that the majority of labeled structures seen with fast axonal transport in the upper dorsal horn are not synapses but are myelinated and nonmyelinated axons. Labeled synapses were the same types as those undergoing degeneration following rhizotomy: round vesicle profiles, central synaptic profiles and LGV profiles. Each of the labeled types was distributed throughout the upper laminae, with the exception of LGV profiles which are uncommon in layers deep to the outer zone of the gelatinosa. It is concluded that fast axon transport autoradiography is not a selective label for synapses in the cord and light microscopic autoradiography does not provide direct estimates of synaptic densities in the dorsal horn.

219 citations

References
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Book ChapterDOI
TL;DR: It is emphasized that, in addition to transmission of impulses, the organization of neuroneuronal junctions is likely to include other important properties that cannot be ignored when the morphology of synaptic contacts is being considered.
Abstract: Publisher Summary This chapter focuses on the morphology of specialized neuronal contacts in general and of synaptic contacts in particular. The term “synapse” is used as a morphological term to describe specialized regions of contact between nerve cells and between nerve cells and effector organs. The structure of this specialized region is of crucial importance. Whereas epithelial cells in general show symmetrical contact regions such as the desmosomes and tight junctions the nervous system shows, in addition, asymmetrical contact regions, the “synaptic thickenings”. It is emphasized that, in addition to transmission of impulses, the organization of neuroneuronal junctions is likely to include other important properties. The interaction between neurons by which a nerve cell can maintain or even stimulate the growth and maturation of an innervated structure is likely to involve neuronal contacts, as is the ability of developing and regenerating axons to grow to and make contact with specific cell groups. Although relatively little is known about these aspects of neuroneuronal interaction they cannot be ignored when the morphology of synaptic contacts is being considered.

450 citations

Journal Article
TL;DR: In this paper, the authors used the simplified classification of the tectal layers used by Cragg, Evans & Hamlyn (1954) modified from van Gehuchten (1892) to study the effects of axons and their terminals.
Abstract: One of the major problems of electron microscopy of the central nervous system is to locate with precision the region involved in the degenerative process in grey or white matter. For this reason, the avian optic tectum was chosen to studythe effects of degeneration of axons and their terminals. Axon section is accomplished simply by unilateral removal of the eye so that the optic nerve afferent fibres to the contralateral hemisphere undergo degeneration (Evans & Hamlyn, 1956). Their trunks are easily located by electron microscopy since they enter the tectum as a superficial layer of myelinated fibres and the terminal ramifications and presynaptic processes are also easily located by reference to a discrete double layer of neuronal perikarya marking the deepest limits of their distribution (Evans & Hamlyn, unpublished; Cowan, Adamson & Powell, 1961). This present work follows naturally from the light-microscopic degeneration studies of Evans & Hamlyn (1956) with the Glees (1946) and Nauta-Gygax (1954) methods. The time courses of the two methods are quite distinct, the Glees method showing rings and clubs, absent from normal tectum, at the 7-11-day stage. At 28-30 days the Glees method is negative, but the Nauta-Gygax picture is fully established. Here electron microscopy has been used to follow these changes in the axons and their presynaptic processes in order to relate them to the different mechanisms of the Glees and Nauta techniques. Few attempts have been made so far to study central nervous degeneration with the electron microscope. De Robertis (1956) has described experimental changes in the ventral acoustic nucleus. Bunge, Bunge & Ris (1960, 1961) have reported on experimental demyelination and remyelination in the spinal cord, the axons remaining apparently unaffected. In this account the simplified classification of the tectal layers used by Cragg, Evans & Hamlyn (1954) modified from van Gehuchten (1892) will be used.

145 citations