去甲肾上腺素在脊髓背角的镇痛机制

疹髓背角浅层是传递和调制外周伤害性信息的关键部位。起源于脑干的去甲肾上腺素（NA）能纤维终止脊髓背角,它们释放的NA具有抑制初级传入末梢释放谷氨酸和P物质、增加Ⅱ层（胶状质）抑制性神经活性物质释放的作用。此外,形态学研究提示NA可能直接抑制Ⅰ/Ⅲ层向丘脑传递伤害性信息的投射神经元。NA可能通过以上途径,实现对外周伤害性信息传递的调制而发挥镇痛作用。     

Noradrenergic axon terminals in the substantia gelatinosa of the rat spinal cord

Summary The noradrenergic terminals in the substantia gelatinosa of the dorsal horn of the cervical spinal cord of the rat were investigated by means of the histofluorescence technique and electron-microscopic cytochemistry using the glyoxylic acid-KMnO₄ fixation technique. In accordance with the topographical distribution of fluorescent catecholaminergic fibers, noradrenergic terminals containing small granular vesicles were frequently observed electron microscopically in the outer layer of the substantia gelatinosa. These terminals were most frequently found to appose without showing typical synaptic features, small-caliber dendrites, spine apparatus, and rarely, large caliber dendrites. Only in a few cases, the noradrenergic terminals exhibited typical synaptic contacts with dendritic elements of small size. In addition, noradrenergic terminals apposed non-noradrenergic terminals containing small agranular vesicles. In rats bearing surgical lesions of the dorsal roots, no noradrenergic terminal were found in contact with the degenerated axon terminals in the substantia gelatinosa. These findings suggest that the noradrenergic afferents to the substantia gelatinosa may exert their influence on sensory transmission via dorsal horn cells.     

Organization of the lamina ganglionaris of the optic lobe of the butterfly Pararge aegeria (Linné) (Lepidoptera : Satyridae)

The present work reports on a neuroanatomical study of the butterfly Pararge aegeria (Lepidoptera : Satyridae) focusing on the lamina ganglionaris underlying two different regions of the retina of the compound eye: the dorsal rim area and the large dorsal region. No differences between both lamina regions, concerning the structure of the cartridges and the morphology of the identified neurons, could be detected. After passing the basement membrane, the visual cell axons are organized in retinotopic bundles (pseudocartridges), in which the axons of the 9 visual cells (V1 and 5, D2, 4, 6, 8, H3 and 7, B9) are arranged in the same way as in the retina. In the pseudocartridge there are no synaptic contacts. Before entering the lamina cartridge, the bundles rotate 90 °. The cartridges are joined by the fibres of 4 monopolar cells (L1, L2, L3 and L4), which could be identified and located inside the lamina cartridges in serial EM-sections. Golgi impregnations revealed the morphology of these fibres. Thus, the regional specialization of the retina (dorsal rim area and large dorsal region) does not seem to be reflected at the level of the first visual neuropil. Additionally, the cartridges of both lamina regions were investigated qualitatively for synaptic contacts among fibres. In addition to monadic chemical synapses and multiple contact synapses with presynaptic ribbons, cell contacts are also facilitated by invaginations and bridges. These cellular interactions and their functional implications are discussed.     

Ultrastructural features of cytofilaments within mammalian endothelial cells

Summary A submicroscopic study of the endothelium lining the blood capillaries and arterioles contained in the Cyon's nerve was made. The cytoplasm of some endothelial cells was found containing bundles of thin filaments. These measure about 60 Å in diameter, and do not show any cross striation, nor contacts with other cytoplasmic components. They are oriented parallel to each other and to the cell surface. No attachment plate of cytofilaments to the plasma membrane was seen. The filamentous structures were mostly found within the supranuclear cytoplasm. The endothelial cells in question never showed contacts with axons.In the light of these findings it can be advanced the view that the cytofilaments present in endothelial cells are supportive in function; namely they may confer a higher elasticity to these cells, subject to continuous pressure and morphological variations.

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Riassunto Lo studio ultrastrutturale dell'endotelio di piccoli vasi sanguigni contenuti nel nervo cardio-aortico depressore di Cyon del coniglio ha consentito di rilevare la presenza in alcune cellule endoteliali di esili filamenti raggruppati in fasci più o meno numerosi. Detti citofilamenti presentano uno spessore di circa 60 Å, occupano per lo più il citoplasma sopranucleare e sono orientati parallelamente tra loro e rispetto alla superficie cellulare. Essi non mostrano struttura periodica né rapporto alcuno, se non di semplice contiguità, con altre componenti citoplasmatiche. Non presentano, inoltre, punti di attacco sulla membrana cellulare, né connessioni con fibre nervose. Numerose le vescicole pinocitotiche osservate lungo i bordi superficiale e basale delle cellule endoteliali in oggetto.In base a tali reperti si avanza l'ipotesi che i citofilamenti endoteliali svolgano una funzione di sostegno nell'ambito del citoplasma, e siano capaci di conferire un più elevato grado di elasticità all'endotelio vasale, soggetto a continue variazioni di pressione e di forma.

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Dedicated to Prof. Wolfgang Bargmann on his 60th birthday.—This investigation was supported in part by a grant from the Italian C.N.R.

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The author wishes to thank Dr. Pasquale Romeo for his kind help in the preparation of the paper, and Mr. Ciro Paesano for making the photographic prints.     

An electron microscopical study of developing sympathetic neurons in man

Summary An electron microscopic study has been made of the sympathetic ganglia of a 15 and a 17 week old male human fetus. The fetal sympathetic neurons were densely packed in a scanty connective tissue matrix which also contained blood vessels. The fetal sympathetic neurons had a large, electron-light nucleus with one or two nucleoli, and was of a somewhat mottled appearance due to irregularly dispersed aggregates of fine and coarse granules. The perikaryon usually formed a thin envelope around the nucleus and contained, except for large pigment granules, all intracytoplasmic structures which were also found in mature sympathetic neurons. Adjacent sympathetic cells were either in immediate contact, or slightly separated by a wedge of electron-light satellite expansions, or lined by primitive axons. The satellite cells were in the early state of development. Electron-dense axons either stood side by side with, or were slightly engulfed by light Schwann cell expansions and formed distinct bundles surrounded by a common basement membrane. There was practically no trace of myelin formation or Schwann cell wrapping characteristic for unmyelinated fibers as seen in the adult.This investigation was supported (in whole) by United States Public Health Service Grant NB-01879-05, Institute for Nervous Diseases and Blindness.Grateful acknowledgment is made to Professor Dr. John Lind who madea vailable the fetal material through the Laboratory of Prenatal Growth and Development, Karolinska Institutet, Stockholm, Sweden.The authors wish to thank Docent Dr. Gunnar Bloom who provided the facilities necessary to prepare the fetal material for electron microscopical examination, in his laboratory for Cell Research, Karolinska Institutet, Stockholm, Sweden.     

Light microscopic autoradiographic localization of [3H] substance P binding sites in rat thoracic spinal cord

We have used light microscopic autoradiography to look for the distribution of [³H] substance P receptors in the thoracic spinal cord of the rat. High densities of autoradiographic grains were localized to the intermedialateral cell column, the central canal and the substantia gelatinosa of the dorsal horn.     

Transganglionic regulation and fine structural localization of lectin-reactive carbohydrate epitopes in primary sensory neurons of the rat

Summary Light- and electron microscopic lectin histochemical studies showed that small dorsal root ganglion cells of the rat projecting to substantia gelatinosa Rolandi (Lamina II) contain terminal -d-galactose carbohydrate epitopes: while those projecting to Waldeyer's marginal zone (Lamina I) and the outer part of Lamina II contain terminal -d-galactose residues. These glycoconjugates are manufactured in the Golgi apparatus and transported to preterminal and terminal axoplasmic surface membranes. Both of the axolemmal carbohydrate moieties were shown to be subjected to transganglionic regulation, even though the effects of transganglionic degenerative atrophy become evident considerably later than the depletion of axoplasmic marker substances like fluoride resistant acid phosphatase and thiamine monophosphatase.Dedicated to Professor Dr. T.H. Schiebler on the occasion of his 65th birthdaySupported by research grants No. 527 from the Hungarian Ministry of Health and No. 05-065 from the Hungarian Academy of Sciences.     

The fine structure of cephalopod blood vessels II. The vessels of the nervous system

Summary Blood vessels of the perioesophageal nerve ganglia (brain) of Octopus vulgaris and the stellate ganglia of Sepia officinalis are described. The vessels have an incomplete endothelium, a complete basement membrane and a complete investment of pericytes. The pericytes are joined by specialised membrane junctions but these are not tight junctions. The main type of neuron/vessel arrangement is one where there is a collagen-filled space between the pericytes and the surrounding glial cells. Axons or neurons are sometimes applied directly to the vessel pericytes and in the neuropil, pericytes contact glial cells that ensheath bundles of axons. Blood spaces between neurons are also present.We would like thank Professor J. Z. Young and Dr. E. G. Gray for encouragement and advice, Mrs. Jane Astafiev for drawing Fig. 11, Mr. S. Waterman for photographic assistance and Miss Cheryl Martin for secretarial and other assistance.     

Somatostatinergic nerves in the cervical spinal cord of the monkey

Somatostatinergic nerves in the spinal cord of the monkey were investigated utilizing immunohistochemistry with various antibodies against synthetic somatostatin. In contrast to earlier investigations, it is shown that somatostatinergic nerve endings occur in most of the areas of the grey matter of the spinal cord. The somatostatinergic axons are, however, characteristically distributed in three main regions: (1) Densely-packed endings are seen in lamina II of the substantia gelatinosa, forming a crescent-shaped pattern in the columna dorsalis. Somatostatin immunoreactivity is also seen in lamina I and in the Lissauer tract. (2) A fine network of fibers is observed around the central canal; the endings are concentrated on special cell bodies. Some single perikarya are also stained in this region. (3) A loose network of single fibers is found ending on perikarya of the columna lateralis or ventralis. The perikarya of the nerve axons, with the exception of those terminating in the columna dorsalis, have as yet not been identified. In order to better understand the somatostatinergic system of the spinal cord, these newly-detected somatostatinergic nerves must be studied and their exact pathways analyzed.     

Studies on the receptors in Ciona intestinalis

Summary A photoreceptor type structure not previously described has been found in the dorsal wall of the cerebral vesicle of the tadpole larva of Ciona intestinalis. The membranes of this receptor are organised as tubules some 60–100 nm in diameter and up to 1.5 m long. The tubules are confined in bundles about 1.5 m in diameter, which extend from the cell surface into the cavity of the cerebral vesicle. These tubules are similar to those in the rhabdomeric type of photoreceptor. However, in the cells from which the tubule processes arise are structures typical of the bases of cilia, and found in ciliary type photoreceptors.I should like to thank Professor J. Z. Young, F. R. S. for his continuing encouragement and help, and Dr. R. Bellairs for the use of electron microscope facilities. Mr. R. Moss and Mrs. J. Hamilton gave excellent technical assistance.     

Fine structure of the respiratory lamellae of teleostean gills

Summary The blood-water pathway in respiratory lamellae of teleostean gills consists of an epithelial layer one or two cells thick, a basal lamina and a thin layer of cytoplasm which lines the blood lacunae. This layer of cytoplasm is formed by flange-like extensions of the pillar cells. The resulting location of the pillar cell perikarya between the surfaces of the blood lacunae is probably of paramount importance for maintenance of the flattened form of the lamellae.Collagenous bundles traverse the pillar cells within tubes formed by infolding of the cellular surface. These bundles, which are oriented normal to the flattened aspect of the lamellae, no doubt provide further protection against distension or collapse of the blood spaces. A compartment filled with collagenous tissue is interposed between the basal lamina and the lining layer of the lacunae in some of the species studied.Regulation of blood flow to the respiratory surfaces is thought to result in part from contraction of the pillar cells. This contractility presumably resides in tracts of filaments which course through the cytoplasm of the pillar cells parallel to the collagenous bundles. Since nervous tissue has not been demonstrated within the gill lamellae it is possible that contraction of the pillar cells is under some form of hormonal control, although existence of local control mechanisms (e.g. self-stimulation of the cells as a result of anoxia) is not excluded.Within the limited number of species studied, the structure of the blood-water pathway does not appear to be correlated with the characteristics of the normal habitat of a particular species.This work was performed during the tenure of a post doctoral traineeship under USPHS Grant 5 T 1 GM-136 to the Department of Biological Structure, University of Washington.Particular thanks are due Dr. John H. Luft of the University of Washington for his advice and criticism while this work was in progress and to Drs. Douglas Kelly, James Koehler and Daniel Szollosi for critical assistance with the manuscipt.     

Fine structure of smooth muscle and neuromuscular junctions in the optic tentacles of Helix aspersa and Limax flavus

Summary The smooth muscle cells studied contain a central core of thick and thin myofilaments surrounded by a peripheral layer of myofilament-free cytoplasm. Numerous vesicles, tubules, microfilaments, mitochondria and fine granules are present in the peripheral cytoplasm. Glycogen particles are distributed in large or small groups in both the peripheral cytoplasm and among the myofilaments. In contracted muscle cells the peripheral cytoplasm bulges out at regular intervals into the intercellular connective tissue. Numerous close contacts between single, usually naked, axons and these cytoplasmic protrusions occur. The axons at these contacts contain numerous small (500 Å in diameter) and large vesicles (800–1000 Å in diameter). Sometimes a number of axons simultaneously form close contacts with a muscle cell. These close contacts are considered to be the sites at which transmitter is released and acts on the muscle cell membrane.I wish to thank Professor G. Burnstock for making laboratory facilities available. This work has been supported by the Australian Research Grants Committee.     

The ultrastructure of the test of the tadpole larva ofCiona intestinalis

Summary The test of the tadpole larva ofCiona intestinalis consists of an amorphous background substance in which are long 4–7 nm fibrils. There is a narrow outer dense region of the test where both the background material and the test fibrils are more concentrated and orientated. Fibrils of similar dimensions are found in the epithelial cells below the test, and also in cells associated with the outside surface of the test. No such fibrils are found in the cells located within the test substance. There are some regions where the external cell membrane of the epithelial cells is indistinct and in these regions the fibrils of the test are continuous with the fibrils within the epithelial cells. No large or small vesicles opening from the epithelial cells into the test have been seen.This evidence has been interpreted as support for the tunicization theory of test formation. It is suggested that the cells within the test are the source of the polyphenols that are necessary for quinone tanning that gives rigidity to the test.The fibril-containing cells outside the test probably add fibres to the cuticular region of the test.I wish to thank ProfessorJ. Z. Young, F.R.S. for much advice and encouragment, also Dr.R. Bellairs for the use of electron microscope facilities and Mr.R. Moss and Mrs.J. Hamilton for skillful technical assistance.     

A modified peroxidase--antiperoxidase procedure for improved localization of tissue antigens: localization of substance P in rat spinal cord

A procedure is presented which modifies the Sternberger peroxidase--antiperoxidase (PAP) technique in order to visualize additional amounts of immunodeposits representing the antigen substance (SP) in 5-micrometer paraffin tissue sections of rat spinal cord. For increased sensitivity, the new procedure utilizes a "double bridge" and diaminobenzidine in low pH buffer. The modifications have made possible the visualization of immunoreactive beaded processes and punctate bodies, which were then traced to determine patterns of SP circuitry. Using the modified PAP procedure, the greatest number of immunoreactive processes appeared in the dorsal horn, where some punctate bodies and varicose processes could be seen adjacent to the myelinated afferent fiber bundles that penetrate the substantia gelatinosa as dorsal root collaterals. Additional immunoreactive processes and punctate bodies coursed through the myelinated afferent fiber bundles that penetrate the dorsolateral white matter, and extend into the intermediolateral gray region. Substance P was also identified within immunoreactive processes found in Rexed's laminae V and VI, as well as the central canal region, the dorsal gray commissure, and the ventral gray and white commissures. Since the modifications improved the visualization of SP-containing processes in sparsely populated regions of the spinal cord, especially the ventral horn, they may be useful in demonstrating other antigens that normally occur in small quantities within tissues.     

The reticular substance of the medulla oblongata of the albino rat

Summary The region of the reticular giganto-cellular nucleus, perfused with formalin and postfixed in osmium tetroxide, was studied with histochemical and electron microscopic techniques. The perikarya of the neurons have two zones. The peripheral cytoplasm contains Nissl bodies, mitochondria, and free RNP particles. The juxtanuclear cytoplasm contains the Golgi complex, mitochondria, RNP particles and dense bodies. The nucleus is indented and has a prominent nucleolus and a paranucleolar body. Dense bodies are found along the axon and dendrites as well. Three different types of synapses are described and two types of synaptic vesicles (spherical and ellipsoidal) are shown.The capillary endothelium shows microvilli and marginal flaps. The endothelial cytoplasm contains vacuoles, micropinocytotic vesicles, and a few dense bodies. Processes of pericapillary cells, surrounded by a basement membrane, also contain dense bodies. The dense bodies found in the neurons and endothelial cells show acid phosphatase activity. On the basis of their morphology and their enzymatic activity these bodies are identified as lysosomes.Partially supported by a school grant No RF 62051 from the Rockefeller Foundation, New York, USA, and Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina.Fellows of the Consejo National de Investigaciones Científicas y Técnicas, Argentina. The authors wish to thank Dr. Mario H. Burgos for his constant interest and criticism, and to Dr. Eduardo Rodriguez Echandia and Dr. Fabio L. Sacerdote for their valuable assistance.     

Synaptic organization in the lateral geniculate nucleus of the monkey

Summary The synaptic organization in the lateral geniculate nucleus of the monkey has been studied by electron microscopy.The axon terminals in the lateral geniculate nucleus can be identified by the synaptic vesicles that they contain and by the specialized contacts that they make with adjacent neural processes. Two types of axon terminal have been recognized. The first type is relatively large (from 3–20 ) and contains relatively pale mitochondria, a great many vesicles and, in normal material, a small bundle of neurofilaments. These terminals have been called LP terminals. The second type is smaller (1–3 ), contains darker mitochondria, synaptic vesicles, and no neurofilaments. These have been called SD terminals.Both types of terminal make specialized axo-somatic and axo-dendritic synaptic contacts, but the axo-somatic contacts are relatively rare. In addition the LP terminals frequently make specialized contacts with the SD terminals, that is, axo-axonal contacts, and at these contacts the asymmetry of the membranes is such that the LP terminal must be regarded as pre-synaptic to the SD terminal.The majority of the synaptic contacts are identical to those that have been described previously (Gray, 1959 and 1963a) but, in addition, a new type of contact has been found. This is characterized by neurofilaments that lie close to the post-synaptic membrane, and by an irregular post-synaptic thickening. Such filamentous contacts have been found only where an LP terminal contacts a dendrite or a soma.The degeneration that follows removal of one eye demonstrates that the LP terminals are terminals of optic nerve fibres. The origin of the SD terminals is not known.The glial cells often form thin lamellae around the neural processes and tend to isolate synaptic complexes. These lamellae occasionally show a complex concentric organization similar to that of myelin.It is a pleasure to thank Prof. J. Z. Young for advice and encouragement and Dr. E. G. Gray for the considerable help he has given us. Dr. J. L. de C. Downer gave us much help with the care of the animals and with the operations. We also wish to thank Mr. K. Watkins for technical assistance and Mr. S. Waterman for the photography.     

Synaptic organization of substance P, glutamate and GABA-immunoreactive boutons on functionally identified neurons in cat spinal deeper dorsal horn

In order to determine how nociceptive input conveyed by the C-fibers terminating in superficial lam-inae of the spinal cord reaches the wide dynamic range (WDR) cells in deeper dorsal horn, which functions as ascend-ing projection pathway, the morphological features of some WDR cells in the deeper dorsal horn of the cat lumbar spinal cord were studied by intracellular injection of horseradish peroxidase and physiological characterization. One of the fully stained neurons with somata in lamina V and dendrites that entered lamina Ⅱ were examined by electron mi-croscopy. Immunogold staining of ultrathin sections through the labeled proximal dendrites in lamina Ⅱ revealed that these dendrites received numerous synapses from substance P and glutamate immunoreactive (IR) axons, which were considered originating from C-fibers. In addition, many GABA-IR terminals were found presynaptic to the labeled dendrites. The results, therefore, suggest that the information carried by primary afferent can be sent from t     

A quantitative study of synaptic interconnections in the dorsal lateral geniculate nucleus of the cat

Summary 2,700 synaptic contacts have been classified according to criteria described in an accompanying paper and the results summarized in tabular form. Only about 20% of the synaptic contacts in laminae A and A1 are formed by axons identifiable as retinogeniculate fibers. About 1/4 of these retinogeniculate synapses are axo-axonal. Approximately 45% of the contacts in these laminae are formed by axons tentatively identifiable as corticogeniculate fibers; about 35% by presumed intrageniculate fibers. Close to one half of the synapses occur in encapsulated synaptic zones, where grapelike dendritic appendages are related mainly to intrageniculate and retinogeniculate axons, and about half lie in interstitial zones, where corticogeniculate and some intrageniculate axons contact distal dendritic segments.Regions of the nucleus receiving from peripheral parts of the retina have relatively more corticogeniculate synapses, and have fewer intrageniculate synapses in the encapsulated zones than do regions receiving from the central parts of the retina.Most of the tissue in lamina B resembles the interstitial zones of laminae A and A1 and over 2/3 of the contacts in lamina B may prove to be corticogeniculate. The retinogeniculate fibers in this lamina are associated with relatively few other axons in simple, small encapsulated zones.Supported by Grant NB 06662 from the USPHS. The skillful technical assistance given by Mrs. E. Langer during the course of this work is gratefully acknowledged.     

Electron microscopy of degeneration in the lateral olfactory tract and plexiform layer of the prepyriform cortex of the rat

Summary The synaptic organization of the plexiform layer of the prepyriform cortex in the rat has been studied with the electron microscope both in the normal and after ipsilateral olfactory bulb removal. Survival times ranged from six hours to three months.In normal preparations synaptic contacts occur mainly on dendritic branches, spines or lateral projections. Gray's Type I contacts are most frequent and Type II contacts usually contain flattened vesicles after formalin fixation.Degeneration of the presynaptic bags begins within 24 hours after the lesion and some degenerated bags are still seen after three months survival. During this time degenerated bags are apparently removed by astroglia but the spine tips appear to be unaffected by the phagocytosis. Glia or other processes may come to occupy the denervated sites. The evidence for possible reestablishment of new contacts is considered.The severed axons show a characteristic mode of degeneration and at three months some appear to be phagocytosed by oligodendroglia which also contain lamellated inclusion bodies.This study represents a part of a thesis accepted in fulfillment of requirements for the degree of Doctor of Philosophy at the University of London (England), June 1966.This investigation was supported in part by a U.S. Public Health Service Fellowship NB 20-844 from the N.I.N.D.S. while the author was a postdoctoral fellow at the Anatomy Department, University College, London, England, and by grants NB 02896 and NB 04053 from the N.I.N.D.S. The author gratefully acknowledges this support and would also like to thank Professors J. Z. Young and E. G. Gray for encouragement and advice throughout the course of this study.     

Electron microscope studies on the structure of collagen fibrils by negative staining

Summary Electron microscope studies on collagen from rat-tail tendon using a negative staining technique have indicated the presence of filaments 15–20 Å in diameter within the fibres. These filaments are thought to correspond to the collagen macromolecule.We would like to thank Prof. R. A. McCance for supplying the specimens of fowl tendon used in this investigation, and Dr. F. H. C. Crick, Dr. S. Fitton-Jackson and Dr. T. Gillman for a number of valuable discussions. One of us (W. J. T.) wishes to thank the Medical Research Council for financial support during this work.