Comprehensive Physiology Wiley Online Library
For Librarians For Authors Editors About

Structure of the Synapse

J. E. Heuser, T. S. Reese

10.1002/cphy.cp010108

Source: Supplement 1: Handbook of Physiology, The Nervous System, Cellular Biology of Neurons

Originally published: 1977

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Structure of the Presynaptic Active Zone
2 Recycling of Synaptic Vesicles
3 Vesicle Turnover and Transmitter Metabolism
4 Vesicles and Transmitter in Adrenergic Synapses
5 Ultimate Origin and Fate of Synaptic Vesicles
6 Development and Degeneration of Synaptic Terminals
7 Glial and Schwann Cells Next to Synaptic Terminals
8 Structure of the Postsynaptic Active Zone
Figure 1. Figure 1.

Thin section of synapse on dendrite in superior olive. Two specializations of the presynaptic membrane are indicated by large arrows. Each specialization is composed of several tufts of dense material, around which synaptic vesicles nestle. Opposite the presynaptic specializations are specialized regions of the postsynaptic membrane at which a continuous layer of dense fuzz is applied to its inner surface. Such membrane specializations and associated synaptic vesicles comprise a synaptic complex which has come to be regarded as the active zone of the synapse. Coated vesicles (small arrow), small cisternae, and mitochondria are other typical organelles found in presynaptic terminals in the CNS. Many synaptic terminals in the CNS are capped by astrocytic processes indicated here at A. (Micrograph supplied by R. Perkins.) ×60,000.
Figure 2. Figure 2.

Freeze‐fractured synapse of a parallel fiber (P) onto the spine (S) of a Purkinje cell dendrite in the molecular layer of the cerebellum. The cluster of particles (large arrow) in this platinum replica of the remaining external leaflet of the fractured spine membrane (S) is thought to represent the postsynaptic active zone of this synapse. Opposite this postsynaptic specialization the axoplasm of the cross‐fractured parallel fiber (P) contains a number of synaptic vesicles and the cytoplasmic leaflet of its presynaptic membrane displays a cluster of particles in the narrow region where it has been split (smaller arrow). Platinum deposits are dark, leaving light shadows, ×80,000.
Figure 3. Figure 3.

Replica of a freeze‐fracture through cerebellar molecular layer which has struck a climbing fiber (C) where it contacts the spines (S) of a Purkinje cell dendrite (D). One of the dendritic spines (lower right) can be traced to its orgin from the dendrite. At sites of synaptic contact, the outer leaflet of the climbing fiber plasmalemma is indented and these indentations display a number of tiny deformations (arrow) which are thought to be sites where synaptic vesicles were caught in the process of exocytosis. Such deformations are characteristic of the active zones of CNS synapses. Surrounding the active zones are larger plasmalemmal deformations which are thought to be stages of coated vesicle formation from the presynaptic membrane (large arrow). Platinum deposits are white in this picture and shadows are black. × 120,000.
Figure 4. Figure 4.

Longitudinal section through a terminal branch of a neuromuscular junction in frog sartorius muscle. Synaptic vesicles cluster around specialized regions of the presynaptic membrane (asterisks) where it protrudes slightly toward the opposing folds in the muscle membrane. These regions of the presynaptic membrane are subtended by a dense cytoplasmic material which forms bands that face the mouths of muscle folds. At the tops of the folds the postsynaptic membrane of the muscle is also underlaid by a dense material that may represent its active or receptive zone. Freeze‐fracture views of this region are shown in Figs. 5 and 13. The terminal is sheathed on a Schwann process (S) which intrudes fingers (S at upper right) between the terminal and the muscle, × 40,000.
Figure 5. Figure 5.

Freeze‐fractured neuromuscular junction from an electrically stimulated frog sartorius muscle, viewed from outside the nerve terminal to observe the cytoplasmic leaflet of its split membrane. Ridges on the surface of the nerve terminal (large arrows) face folds (F) in the surface of the muscle. Small dimples in the surface of the terminal beside the ridges (small arrows) are thought to be loci where synaptic vesicles were fixed as they fused with the plasmalemma. Because very few such deformations occur in unstimulated terminals or in terminals stimulated in Ringer's solution containing magnesium to block transmitter release, vesicles are thought to fuse with the plasmalemma only during transmitter discharge. Platinum deposits white, shadows dark. ×50,000.
Figure 6. Figure 6.

Cross section of a neuromuscular junction in a rat diaphragm whose natural activity had been maintained until the moment of fixation. Coated vesicles appear to have been caught in the act of formation at several regions of the plasmalemma (arrows), including the invaginated regions that surround a Schwann process (S). Other coated vesicles are free in the axoplasm or coalesce with larger vacuoles or cisternae that are dispersed among the synaptic vesicles (top arrow). The dense postsynaptic specialization is particularly prominent at the tops of certain folds, where the muscle membrane is cut obliquely (asterisk). × 100,000.
Figure 7. Figure 7.

Freeze‐fractured cerebellar glomerulus. A palisade of granule cell dendrites (G) bulges against a mossy fiber terminal whose outer leaflet is exposed (M, below). The fracture then turns across the cytoplasm of the mossy terminal, exposing synaptic vesicles. The small deformations (upper arrows) on the external leaflet of its fractured plasmalemma are situated where coated vesicles are seen to pinch off in thin sections. The small pits at active zones (between opposed arrows) are imprints of fields of large particles which characterize the cytoplasmic half of the presynaptic membrane at most CNS synapses. Platinum deposits are white, shadows black. × 80,000.
Figure 8. Figure 8.

Higher magnification of plasmalemmal deformations in the external leaflet of the fractured presynaptic membrane of a mossy fiber in a cerebellar glomerulus. Such deformations are usually found just beside an active zone of a synapse, which is demarcated here by the opposed arrows. In thin sections, coated vesicles appear to pinch off from the regions where these plasmalemmal deformations occur, so these deformations are regarded as sequential stages in the formation of coated vesicles. The sequence of stages could be 1: large particles gather into clusters in the presynaptic plasmalemma, 2: regions with particle clusters become deformed or curved inward toward the axoplasm (thin sections through these deformed regions have a characteristic cytoplasmic coat), 3: the particle‐rich region had presumably formed a nearly complete vesicle which fractured off with the axoplasm, leaving a crater at its last point of contact with the surface. Platinum deposits dark, shadows light. × 200,000.
Figure 9. Figure 9.

Synapse of an electroreceptor cell on its afferent sensory axon, from the skate. Synaptic vesicles cluster along the presynaptic ribbon, and at its base appear to fuse with the presynaptic plasmalemma (small arrows). Coated pits (large arrows) are thought to be a stage in the formation of coated vesicles. × 65,000.
Figure 10. Figure 10.

Adrenergic varicosity in the rat vas deferens. A large proportion of the synaptic vesicles that cluster in such varicosities contain electron‐dense cores of various sizes and shapes. It has so far not been possible to define regions in such varicosities where the presynaptic membrane is specialized into discrete active zones. × 110,000.

From Basbaum 11
Figure 11. Figure 11.

Reciprocal synapse between granule cell and mitral cell dendrites in the glomerulus of the olfactory blub. Synaptic vesicles in the granule cell dendrite (G) cluster near a type II junction which lacks a prominent coat of cytoplasmic dense material on the postsynaptic membrane. Vesicles in the mitral dendrite (M) cluster near a type I junction which is characterized by a prominent cytoplasmic coat beneath the postsynaptic membrane at the active zone. Coated vesicles (arrows) are caught in the process of pinching off from both the mitral and granule cell membranes. At reciprocal synapses adjacent active zones are aimed in opposite directions. × 100,000.
Figure 12. Figure 12.

Freeze‐fractured reciprocal synapse from the same region of the olfactory bulb as that shown in Fig. 11. The external leaflet of a fractured granule cell plasmalemma is in full view (G) and contains a cluster of particles where this terminal is postsynaptic to a mitral dendrite (M, at right). The plasmalemmal deformations scattered about on this surface (arrow) are thought to be sites at which coated or synaptic vesicles are fused with the plasmalemma. A similar plasmalemmal deformation, viewed from the opposite side, is present on the cytoplasmic leaflet of the mitral cell membrane (arrow at right). Synaptic vesicles are visible in the fractured axoplasm of the granual cell terminal (asterisk). Platinum deposits white, shadows dark. ×80,000.
Figure 13. Figure 13.

Frog neuromuscular junction frozen without fixation during a recovery period following intense stimulation. In this view of the external leaflet of the plasmalemma of the nerve terminal (lower half) are a number of crater‐shaped deformations which are situated in regions where coated vesicles are known to form, including regions of the plasmalemma elevated by the Schwann processes (S). At the top, the nerve terminal is torn away completely to expose the active zone of the muscle membrane, which is characterized by the high concentrations of large particles that adhere to its cytoplasmic leaflet during fracturing. These particles form an almost continuous mat beneath the nerve terminal and occur in patches of high density immediately beside the terminal. No patches of particles are present in the depths of the postsynaptic folds (F) where sarcolemmal caveolae (arrow at left), like those over the rest of the surface of the muscle (arrow at right), are found. Platinum deposits dark, shadows light. ×75,000.


Figure 1.

Thin section of synapse on dendrite in superior olive. Two specializations of the presynaptic membrane are indicated by large arrows. Each specialization is composed of several tufts of dense material, around which synaptic vesicles nestle. Opposite the presynaptic specializations are specialized regions of the postsynaptic membrane at which a continuous layer of dense fuzz is applied to its inner surface. Such membrane specializations and associated synaptic vesicles comprise a synaptic complex which has come to be regarded as the active zone of the synapse. Coated vesicles (small arrow), small cisternae, and mitochondria are other typical organelles found in presynaptic terminals in the CNS. Many synaptic terminals in the CNS are capped by astrocytic processes indicated here at A. (Micrograph supplied by R. Perkins.) ×60,000.



Figure 2.

Freeze‐fractured synapse of a parallel fiber (P) onto the spine (S) of a Purkinje cell dendrite in the molecular layer of the cerebellum. The cluster of particles (large arrow) in this platinum replica of the remaining external leaflet of the fractured spine membrane (S) is thought to represent the postsynaptic active zone of this synapse. Opposite this postsynaptic specialization the axoplasm of the cross‐fractured parallel fiber (P) contains a number of synaptic vesicles and the cytoplasmic leaflet of its presynaptic membrane displays a cluster of particles in the narrow region where it has been split (smaller arrow). Platinum deposits are dark, leaving light shadows, ×80,000.



Figure 3.

Replica of a freeze‐fracture through cerebellar molecular layer which has struck a climbing fiber (C) where it contacts the spines (S) of a Purkinje cell dendrite (D). One of the dendritic spines (lower right) can be traced to its orgin from the dendrite. At sites of synaptic contact, the outer leaflet of the climbing fiber plasmalemma is indented and these indentations display a number of tiny deformations (arrow) which are thought to be sites where synaptic vesicles were caught in the process of exocytosis. Such deformations are characteristic of the active zones of CNS synapses. Surrounding the active zones are larger plasmalemmal deformations which are thought to be stages of coated vesicle formation from the presynaptic membrane (large arrow). Platinum deposits are white in this picture and shadows are black. × 120,000.



Figure 4.

Longitudinal section through a terminal branch of a neuromuscular junction in frog sartorius muscle. Synaptic vesicles cluster around specialized regions of the presynaptic membrane (asterisks) where it protrudes slightly toward the opposing folds in the muscle membrane. These regions of the presynaptic membrane are subtended by a dense cytoplasmic material which forms bands that face the mouths of muscle folds. At the tops of the folds the postsynaptic membrane of the muscle is also underlaid by a dense material that may represent its active or receptive zone. Freeze‐fracture views of this region are shown in Figs. 5 and 13. The terminal is sheathed on a Schwann process (S) which intrudes fingers (S at upper right) between the terminal and the muscle, × 40,000.



Figure 5.

Freeze‐fractured neuromuscular junction from an electrically stimulated frog sartorius muscle, viewed from outside the nerve terminal to observe the cytoplasmic leaflet of its split membrane. Ridges on the surface of the nerve terminal (large arrows) face folds (F) in the surface of the muscle. Small dimples in the surface of the terminal beside the ridges (small arrows) are thought to be loci where synaptic vesicles were fixed as they fused with the plasmalemma. Because very few such deformations occur in unstimulated terminals or in terminals stimulated in Ringer's solution containing magnesium to block transmitter release, vesicles are thought to fuse with the plasmalemma only during transmitter discharge. Platinum deposits white, shadows dark. ×50,000.



Figure 6.

Cross section of a neuromuscular junction in a rat diaphragm whose natural activity had been maintained until the moment of fixation. Coated vesicles appear to have been caught in the act of formation at several regions of the plasmalemma (arrows), including the invaginated regions that surround a Schwann process (S). Other coated vesicles are free in the axoplasm or coalesce with larger vacuoles or cisternae that are dispersed among the synaptic vesicles (top arrow). The dense postsynaptic specialization is particularly prominent at the tops of certain folds, where the muscle membrane is cut obliquely (asterisk). × 100,000.



Figure 7.

Freeze‐fractured cerebellar glomerulus. A palisade of granule cell dendrites (G) bulges against a mossy fiber terminal whose outer leaflet is exposed (M, below). The fracture then turns across the cytoplasm of the mossy terminal, exposing synaptic vesicles. The small deformations (upper arrows) on the external leaflet of its fractured plasmalemma are situated where coated vesicles are seen to pinch off in thin sections. The small pits at active zones (between opposed arrows) are imprints of fields of large particles which characterize the cytoplasmic half of the presynaptic membrane at most CNS synapses. Platinum deposits are white, shadows black. × 80,000.



Figure 8.

Higher magnification of plasmalemmal deformations in the external leaflet of the fractured presynaptic membrane of a mossy fiber in a cerebellar glomerulus. Such deformations are usually found just beside an active zone of a synapse, which is demarcated here by the opposed arrows. In thin sections, coated vesicles appear to pinch off from the regions where these plasmalemmal deformations occur, so these deformations are regarded as sequential stages in the formation of coated vesicles. The sequence of stages could be 1: large particles gather into clusters in the presynaptic plasmalemma, 2: regions with particle clusters become deformed or curved inward toward the axoplasm (thin sections through these deformed regions have a characteristic cytoplasmic coat), 3: the particle‐rich region had presumably formed a nearly complete vesicle which fractured off with the axoplasm, leaving a crater at its last point of contact with the surface. Platinum deposits dark, shadows light. × 200,000.



Figure 9.

Synapse of an electroreceptor cell on its afferent sensory axon, from the skate. Synaptic vesicles cluster along the presynaptic ribbon, and at its base appear to fuse with the presynaptic plasmalemma (small arrows). Coated pits (large arrows) are thought to be a stage in the formation of coated vesicles. × 65,000.



Figure 10.

Adrenergic varicosity in the rat vas deferens. A large proportion of the synaptic vesicles that cluster in such varicosities contain electron‐dense cores of various sizes and shapes. It has so far not been possible to define regions in such varicosities where the presynaptic membrane is specialized into discrete active zones. × 110,000.

From Basbaum 11


Figure 11.

Reciprocal synapse between granule cell and mitral cell dendrites in the glomerulus of the olfactory blub. Synaptic vesicles in the granule cell dendrite (G) cluster near a type II junction which lacks a prominent coat of cytoplasmic dense material on the postsynaptic membrane. Vesicles in the mitral dendrite (M) cluster near a type I junction which is characterized by a prominent cytoplasmic coat beneath the postsynaptic membrane at the active zone. Coated vesicles (arrows) are caught in the process of pinching off from both the mitral and granule cell membranes. At reciprocal synapses adjacent active zones are aimed in opposite directions. × 100,000.



Figure 12.

Freeze‐fractured reciprocal synapse from the same region of the olfactory bulb as that shown in Fig. 11. The external leaflet of a fractured granule cell plasmalemma is in full view (G) and contains a cluster of particles where this terminal is postsynaptic to a mitral dendrite (M, at right). The plasmalemmal deformations scattered about on this surface (arrow) are thought to be sites at which coated or synaptic vesicles are fused with the plasmalemma. A similar plasmalemmal deformation, viewed from the opposite side, is present on the cytoplasmic leaflet of the mitral cell membrane (arrow at right). Synaptic vesicles are visible in the fractured axoplasm of the granual cell terminal (asterisk). Platinum deposits white, shadows dark. ×80,000.



Figure 13.

Frog neuromuscular junction frozen without fixation during a recovery period following intense stimulation. In this view of the external leaflet of the plasmalemma of the nerve terminal (lower half) are a number of crater‐shaped deformations which are situated in regions where coated vesicles are known to form, including regions of the plasmalemma elevated by the Schwann processes (S). At the top, the nerve terminal is torn away completely to expose the active zone of the muscle membrane, which is characterized by the high concentrations of large particles that adhere to its cytoplasmic leaflet during fracturing. These particles form an almost continuous mat beneath the nerve terminal and occur in patches of high density immediately beside the terminal. No patches of particles are present in the depths of the postsynaptic folds (F) where sarcolemmal caveolae (arrow at left), like those over the rest of the surface of the muscle (arrow at right), are found. Platinum deposits dark, shadows light. ×75,000.

References
 1. Adrian, E. D., D. W. Bronk, and G. Phillips. Discharges in mammalian sympathetic nerves. J. Physiol. London 74: 115–133, 1932.
 2. Akert, K., K. Pfenninger, C. Sandri, and H. Moor. Freeze‐etching and cytochemistry of vesicles and membrane complexes in synapses of the central nervous system. In: Structure and Function of Synapses, edited by G. D. Pappas and D. P. Purpura. New York: Raven, 1972, p. 67–86.
 3. Altman, J. Coated vesicles and synaptogenesis. A developmental study in the cerebellar cortex of the rat. Brain Res. 30: 311–322, 1971.
 4. Amsterdam, A., I. Ohad, and M. Schramm. Dynamic changes in the ultrastructure of the acinar cell of the rat parotid gland during the secretory cycle. J. Cell Biol. 41: 753–773, 1969.
 5. Anderson, M. J., and M. W. Cohen. Fluorescent staining of acetylcholine receptors in vertebrate skeletal muscle. J. Physiol. London 237: 385–400, 1974.
 6. Anderson, P., and J. C. Eccles. Recurrent inhibition in the hippocampus with identification of the inhibitory cell and its synapses. Nature 198: 540–542, 1963.
 7. Andres, K. H. Mikropinozytose im Zentralnervensystem. Z. Zellforsch. Mikroskop. Anat. 64: 63–73, 1964.
 8. Andres, K. H., and M. Düring. Mikropinozytose in motorischen Endplatten. Naturwissenschaften 53: 615–616, 1966.
 9. Atwood, H. L., F. Lang, and W. A. Moran. Synaptic vesicles. Selective depletion in crayfish excitatory and inhibitory axons. Science 176: 1353–1355, 1972.
 10. Barker, D., and M. C. Ip. Sprouting and degeneration of mammalian motor axons in normal and de‐afferentiated skeletal muscle. Proc. Roy. Soc. London Ser. B 163: 538–559, 1966.
 11. Basbaum, C. B. Effects of magnesium ions on adrenergic nerve terminals. J. Neurocytol. 3: 753–752, 1974.
 12. Berlin, R. D., J. M. Oliver, T. E. Ukena, and H. H. Yin. Control of cell surface topography. Nature 247: 45–46, 1973.
 13. Betz, W., and B. Sakmann. Effects of proteolytic enzymes on function and structure of frog neuromuscular junctions. J. Physiol. London 230: 673–688, 1973.
 14. Birks, R. I. The effects of a cardiac glycoside on subcellular structures within nerve cells and their processes in sympathetic ganglia and skeletal muscle. Am. J. Biochem. Physiol. 40: 303–316, 1962.
 15. Birks, R. I. The fine structure of motor nerve endings at frog myoneural junctions. Ann. NY Acad. Sci. 135: 8–19, 1966.
 16. Birks, R. I. The relationship of transmitter release and storage to fine structure in a sympathetic ganglion. J. Neurocytol. 3: 133–160, 1973.
 17. Birks, R., H. E. Huxley, and B. Katz. The fine structure of the neuromuscular junction of the frog. J. Physiol. London 150: 134–144, 1960.
 18. Birks, R., B. Katz, and R. Miledi. Physiological and structural changes at the amphibian myoneural junction in the course of nerve degeneration. J. Physiol. London 150: 145–168, 1960.
 19. Birks, R., and F. C. Macintosh. Acetylcholine metabolism ganglion. Can. J. Biochem. Physiol. 39: 787–827, 1961.
 20. Birks, R. I., M. C. Mackay, and P. R. Weldon. Organelle formation from pinocytotic elements in neurites of cultured sympathetic ganglia. J. Neurocytol. 1: 311–340, 1972.
 21. Bittner, G. D., and D. Kennedy. Quantitative aspects of transmitter release. J. Cell Biol. 47: 585–592, 1970.
 22. Blakeley, A. G. H., D. P. Dearnaley, and V. Harrison. The noradrenaline content of the vas deferens of the guinea pig. Proc. Roy. Soc. London Ser. B 174: 491–502, 1970.
 23. Blaustein, M. The interrelationship between sodium and calcium fluxes across cell membranes. Rev. Physiol. Biochem. Pharmacol. 70: 34–71, 1974.
 24. Blinzinger, K., and G. Kreutzberg. Displacement of synaptic terminals from regenerating motoneurons by microglial cells. Z. Zellforsch. Mikroskop. Anat. 85: 145–157, 1968.
 25. Bloom, F. E., and G. K. Aghajanian. Cytochemistry of synapses: selective staining for electron microscopy. Science 154: 1575–1577, 1966.
 26. Bloom, F. E., and G. K. Aghajanian. Fine structural and cytochemical analysis of the staining of synaptic junctions with phosphotungstic acid. J. Ultrastruct. Res. 22: 361–367, 1968.
 27. Bodian, D. Synaptic diversity and characterization by electronmicroscopy. In: Structure and Function of Synapses, edited by G. D. Pappas and D. P. Purpura. New York: Raven, 1972, p. 45.
 28. Bowers, B. Coated vesicles in the pericardial cells of the aphid. Protoplasma 59: 351–367, 1964.
 29. Boyne, A. F., T. P. Bohan, and T. H. Williams. Effects of calcium‐containing fixation solutions on cholinergic synaptic vesicles. J. Cell Biol. 63: 780–795, 1974.
 30. Branton, D. Fracture faces of frozen membranes. Proc. Natl. Acad. Sci. US 55: 1048–1056, 1966.
 31. Branton, D. Membrane structure. Ann. Rev. Plant Physiol. 20: 209–238, 1969.
 32. Branton, D. Freeze‐etching studies of membrane structure. Phil. Trans. Roy. Soc. London Ser. B 261: 133–138, 1971.
 33. Brightman, M. W. The distribution within the brain of ferritin injected into cerebrospinal fluid compartments. II. Parenchymal distribution. Am. J. Anat. 117: 193–220, 1965.
 34. Brown, G. L., and W. Feldberg. The acetylcholine metabolism of a sympathetic ganglion. J. Physiol. London 89: 265–283, 1936.
 35. Bunge, M. G. Fine structure of nerve fibers and growth cones of isolated sympathetic neurons in culture. J. Cell Biol. 56: 713–735, 1973.
 36. Bunge, M. B., R. P. Bunge, and E. R. Peterson. The onset of synapse formation in spinal cord cultures as studied by electron microscopy. Brain Res. 6: 728–749, 1967.
 37. Bunt, A. H. Enzymatic digestion of synaptic ribbons in amphibian retinal photoreceptors. Brain Res. 25: 571–577, 1971.
 38. Burnstock, G., and M. E. Holman. Spontaneous potentials at sympathetic nerve endings in smooth muscle. J. Physiol. London 160: 446–460, 1967.
 39. Cajal, S. Ramon, Y. Contribution to the study of the structure of motor plaques. In: Studies on Vertebrate Neurogenesis, edited by L. Guth. Springfield, Ill.: Thomas, 1960, p. 1–432.
 40. Cartaud, J., E. L. Bendetti, J. B. Cohen, J. C. Meunier, and T. P. Changeux. Presence of a lattice structure in membrane fragments rich in nicotinic receptor protein from the electric organ of Torpedo marmotata. FEBS Letters 33: 109–113, 1973.
 41. Cartaud, J., E. L. Benedetti, M. Kasai, and J. P. Changeux. In vitro excitation of purified membrane fragments by cholinergic agonists. IV. Ultrastructure at high resolution of the AchE‐rich and ATPase‐rich microsacs. J. Membrane Biol. 6: 81–88, 1971.
 42. Ceccarelli, B., W. P. Hurlbut, and A. Mauro. Depletion of vesicles from frog neuromuscular junctions by prolonged tetanic stimulation. J. Cell Biol. 54: 30–38, 1972.
 43. Ceccarelli, B., W. P. Hurlbut, and A. Mauro. Turnover of transmitter and synaptic vesicles at the frog neuromuscular junction. J. Cell Biol. 57: 499–524, 1973.
 44. Chamley, J. H., G. E. Mark, G. Campbell, and G. Burnstock. Sympathetic ganglia in culture. I. Neurons. Z. Zellforsch. Mikroskop. Anat. 135: 287–314, 1972.
 45. Clark, A. W., W. P. Hurlbut, and A. Mauro. Changes in the fine structure of the neuromuscular junction of the frog caused by black widow spider venom. J. Cell Biol. 57: 1–14, 1972.
 46. Collier, B. The preferential release of newly synthesized transmitter by a sympathetic ganglion. J. Physiol. London 205: 341–352, 1969.
 47. Collier, B., and F. C. Macintosh. The source of choline for acetylcholine synthesis in a sympathetic ganglion. Can. J. Physiol. Pharmacol. 47: 127–136, 1969.
 48. Colonnier, M. Experimental degeneration in the cerebral cortex. J. Anat. 98: 47–53, 1964.
 49. Colonnier, M. Synaptic patterns on different cell types in the different laminae of the cat visual cortex. An electron microscopy study. Brain Res. 9: 268–287, 1968.
 50. Cotman, C. W., and C. A. Matthews. Synaptic plasma membranes from rat brain synaptosomes: isolation and partial characterization. Biochem. Biophys. Acta 249: 380–394, 1971.
 51. Couteaux, R. In: Le Muscle, Étude de Biologie et de Pathologie, edited by C.C.I.CM.S. Paris: L'Expansion Scientifique. (International Symposium, Royaumont, France), 1952, p. 173–183.
 52. Couteaux, R. Localization of cholinesterases at neuromuscular junctions. Intern. Rev. Cytol. 4: 335–375, 1955.
 53. Couteaux, R. Motor end‐plate structure. In: Structure and Function of Muscle I, edited by G. H. Bourne. New York: Academic, 1960, p. 337.
 54. Couteaux, R. Remarks on the organization of axon terminals in relation to secretory processes at synapses. In: Advances in Cytopharmacology, edited by B. Ceccarelli, F. Clementi, and J. Meldolesi. New York: Raven, 1974, vol. 2, p. 369–379.
 55. Couteaux, R., and M. Pecot‐Dechavassine. Particularités structurales du sarcoplasme sous‐neural. Compt. Rend. 266: 8–10, 1968.
 56. Couteaux, R., and M. Pecot‐Dechavassine. Vésicules synaptiques et poches au niveau des zones actives de la jonction neuromusculaire. Compt. Rend. 271: 2346–2349, 1970.
 57. Couteaux, R., and M. Pecot‐Dechavassine. Les zones spécialisées des membranes presynaptiques. Compt. Rend. 278: 291–293, 1974.
 58. Couteaux, R., and J. Taxi. Recherches histochimiques sur la distribution disactivities cholinesterasiques au mileau de la synapse myo‐neurale. Arch. Anat. Microscop. 41: 352–392, 1952.
 59. Cuenod, M., C. Sandri, and K. Akert. Enlarged synaptic vesicles as an early sign of secondary degeneration in the optic nerve terminals of the pigeon. J. Cell Biol. 6: 605–613, 1970.
 60. Dahlstrom, A., and J. Haggendal. Studies on the transport and life span of amine storage granules in a peripheral adrenergic neuron system. Acta Physiol. Scand. 67: 278–288, 1966.
 61. Dahlstrom, A., J. Haggendal, and T. Hokfelt. The noradrenaline content of the varicosities of sympathetic adrenergic neural terminals in the rat. Acta Physiol. Scand. 67: 289–294, 1966.
 62. Dale, H. H., W. Feldberg, and M. Vogt. Release of acetylcholine at voluntary motor nerve endings. J. Physiol. London 86: 353–380, 1936.
 63. Daniels, M. P., and Z. Vogel. Immunoperoxidase staining of α‐bungarotoxin binding sites in muscle end‐plates shows distribution of acetylcholine receptors. Nature 254: 339–341, 1975.
 64. De Duve, C. The lysosome concept. In: Ciba Symposium on Lysosomes, edited by A. V. S. De Reuck and M. P. Cameron. Boston: Little, Brown, 1963, p. 101–125.
 65. Del Castillo, J., and B. Katz. Biochemical aspects of neuro‐muscular transmission. Progr. Biophys. Biochem. 6: 121–170, 1956.
 66. Dennis, M. J., and R. Miledi. Characteristics of transmitter release at regenerating frog neuromuscular junctions. J. Physiol. London 239: 571–594, 1974.
 67. De Robertis, E. D. P. Changes in the “synaptic vesicles” of the ventral acoustic ganglion after nerve section. Anat. Record 121: 284–285, 1955.
 68. De Robertis, E. D. Submicroscopic changes in the synapse after nerve section in the acoustic ganglion of the guinea pig. An electron microscope study. J. Biophys. Biochem. Cytol. 2: 503–512, 1956.
 69. De Robertis, E. Submicroscopic morphology and function of the synapse. Exptl. Cell Res. Suppl. 5: 347–369, 1958.
 70. De Robertis, E. D. P. Fine structure of synapses in the central nervous system. Proc. Intern. Congr. Neuropathol., 4th, Munich 2: 35–38, 1962.
 71. De Robertis, E. D. P., and H. S. Bennett. Some features of the submicroscopic morphology of synapses in frog and earthworm. J. Biophys. Biochem. Cytol. 1: 47–58, 1955.
 72. De Robertis, E. D. P., and A. Vas Ferreira. Submicroscopic changes of the nerve endings in the adrenal medulla after stimulation of the splanchnic nerve. J. Biophys. Biochem. Cytol. 3: 611–614, 1957.
 73. Diamond, J., and R. Miledi. A study of foetal and new born rat muscle fibers. J. Physiol. London 162: 393–408, 1962.
 74. Diamond, I., and D. Milfay. Uptake of [3H‐methyl]choline by microsomal synaptosomal, mitochondrial and synaptic vesicle fractions of rat brain. The effects of hemicholinium. J. Neurochem. 19: 1899–1909, 1972.
 75. Dickinson, A. H., and T. S. Reese. Morphological changes after electrical stimulation of frog sympathetic ganglia. Anat. Record 175: 306, 1973.
 76. Douglas, W. W., J. Nagasawa, and R. A. Schultz. Coated microvesicles in neurosecretory terminals of posterior pituitary glands shed their coats to become smooth synaptic vesicles. Nature 232: 340–341, 1967.
 77. Dreyer, F., K. Peper, K. Akert, C. Sandri, and H. Moor. Ultrastructure of the active zone in the frog neuromuscular junction. Brain Res. 62: 373–380, 1973.
 78. Droz, B. Smooth endoplasmic reticulum: structure and role in renewal of axonal membrane and synaptic vesicles by fast axonal transport. Brain Res. 93: 1–13, 1975.
 79. Duchen, L. W. An electron microscope comparison of motor endplates of slow and fast skeletal muscle fibers of the mouse. J. Neurol. Sci. 14: 37–45, 1971.
 80. Düring, M. Über die Feinstruktur der motorischen Endplatte von höheren Wirbeltieren. Z. Zellforsch. Mikroskop. Anat. 81: 74–90, 1967.
 81. Eccles, J. C. The Physiology of Synapses. Berlin: Springer Verlag, 1964, p. 17.
 82. Eccles, J. C. The Physiology of Nerve Cells. Baltimore: Johns Hopkins Press, 1957.
 83. Eccles, J. C., and J. C. Jaeger. Relationship between mode of operation and the dimensions of the junctional regions at synapses and motor end organs. Proc. Roy. Soc. London Ser. B. 148: 38–56, 1957.
 84. Edds, M. V. Collateral regeneration of residual motor axons in partially denervated muscles. J. Exptl. Zool. 113: 517–552, 1950.
 85. Edds, M. V. Collateral nerve regeneration. Quart. Rev. Biol. 28: 260–276, 1953.
 86. Eichberg, J., V. P. Whittaker, and R. M. C. Dawson. Distribution of lipids in subcellular particles of guinea pig brain. Biochem. J. 92: 91–100, 1964.
 87. Elfin, L. G. The ultrastructure of the superior cervical sympathetic ganglion of the cat. II. The structure of preganglionic end fibers and the synapses as studied by serial sections. J. Ultrastruct. Res. 8: 441–477, 1963.
 88. Elias, P. M., and D. S. Friend. Vitamin‐A‐induced mucus metaplasia. An in vitro system for modulating tight‐ and gap‐junction differentiation. J. Cell Biol. 68: 173–188, 1976.
 89. Elmqvist, D., and E. Lambert. Detailed analyses of neuromuscular transmission in a patient with the myasthenic syndrome sometimes associated with bronchogenic carcinoma. Mayo Clin. Proc. 43: 689–713, 1968.
 90. Elmqvist, D., and D. M. J. Quastel. Presynaptic action of hemicholinium at the neuromuscular junction. J. Physiol. London 177: 463–482, 1965.
 91. Elmqvist, D., and D. Quastel. A quantitative study of end‐plate potentials in isolated human muscle. J. Physiol. London 178: 505–529, 1965.
 92. Engel, A. G., and T. Santa. Histometric analysis of the neuromuscular junction in myasthenia gravis and in the myasthenic syndrome. Ann. NY Acad. Sci. 183: 46–63, 1971.
 93. Euler, U. S., and N. A. Hillarp. Evidence for the presence of noradrenaline in submicroscopic structures of adrenergic axons. Nature 177: 44–45, 1956.
 94. Euler, U. S., and F. Lishajko. Effect of reserpine on the release of catecholamines from isolated nerve and chromaffin cell granules. Acta Physiol. Scand. 52: 137–145, 1961.
 95. Falls, W. M., and J. S. King. The facial motor nucleus of the opossum: cytology and axosomatic synapses. J. Comp. Neurol. 167: 177–204, 1976.
 96. Falls, W. M., and J. S. King. The facial motor nucleus of the opossum: synaptic endings on dendrites. J. Comp. Neurol. 167: 205–226, 1976.
 97. Fardeau, M. Ultrastructure des jonctions neuro‐musculaires dans la musculative queletlique du cobaye. In: La Transmission Cholinergique de l'Exitation. INSERM Colloque 1972, p. 187.
 98. Farquhar, M. G., and G. E. Palade. Junctional complexes in various epithelia. J. Cell Biol. 17: 375–392, 1963.
 99. Farrell, K. E. Fine structure of nerve fibers in smooth muscle of the vas deferens in normal and reserpinized rats. Nature 217: 279–281, 1968.
 100. Farrell, K. E. The selective depletion of intra‐axonal granular vesicles by reserpine. J. Anat. 103: 207, 1968.
 101. Fertuck, H. C., and M. M. Salpeter. Localization of the acetylcholine receptor by I125 labeled α‐bungarotoxin binding at mouse motor end plates. Proc. Natl. Acad. Sci. US 71: 1376–1378, 1974.
 102. Fillenz, M. A. Fine structure of noradrenaline storage vesicles in nerve terminals of the rat vas deferens. Phil. Trans. Roy. Soc. London Ser. B 261: 319–323, 1971.
 103. Fischbach, G. D. Synapse formation between dissociated nerve and muscle cells in low density cell cultures. Develop. Biol. 28: 407–429, 1972.
 104. Fischbach, G. D., and S. A. Cohen. The distribution of acetylcholine sensitivity over uninnervated and innervated muscle fibers grown in cell culture. Develop. Biol. 31: 147–162, 1973.
 105. Folkow, B. Impulse frequency in sympathetic vasomotor fibers correlated to the release and elimination of the transmitters. Acta Physiol. Scand. 25: 49–76, 1952.
 106. Folkow, B. Neurons control of the blood vessels. Physiol. Rev. 35: 629–663, 1955.
 107. Folkow, B., J. Haggendal, and B. Lisander. Extent of release and elimination of noradrenalin at peripheral adrenergic nerve terminals. Acta Physiol. Scand. Suppl. 307: 1–38, 1967.
 108. Foster, M., and C. S. Sherrington. A Textbook of Physiology. London: Macmillan, part 3, p. 930.
 109. Fox, C. A., K. A. Siegesmund, and C. R. Dulta. The Purkinje cell dendritic branchlets and their relation with parallel fibers: light and electron microscopic observations. In: Morphological and Biochemical Correlates of Neural Activity, edited by M. M. Cohen and R. S. Schnider. New York: Hoeber, 1964 p. 112–141.
 110. Friend, D. S., and H. G. Farquhar. Functions of coated vesicles during protein absorption in the rat vas deferens. J. Cell Biol. 35: 357–376, 1967.
 111. Frontali, N. Catecholamine‐depleting effect of black widow spider venom on iris nerve fibers. Brain Res. 37: 146–153, 1972.
 112. Frye, L. D., and M. Edidin. The rapid intermixing of cell surface antigens after formation of mouse‐human heterokaryons. J. Cell Sci. 7: 319–335, 1970.
 113. Gabella, G. Fine structure of the myenteric plexus in the guinea pig ileum. J. Anat. 111: 69–97, 1972.
 114. Gauthier, G. F., and H. A. Padykula. Cytological studies of fiber types in skeletal muscle. A comparative study of the mammalian diaphragm. J. Cell Biol. 28: 333–354, 1966.
 115. Gonzenbach, H. R., and P. G. Waser. Electron microscope studies of degeneration and regeneration of rat neuromuscular junctions. Brain Res. 63: 167–174, 1973.
 116. Gray, E. G. Axo‐somatic and axo‐dendrite synapses of the cerebral cortex: an electron microscopic study. J. Anat. 93: 420–433, 1959.
 117. Gray, E. G. The granule cells, mossy synapses, and Purkinje spine synapses of the cerebellum: light and electron microscope observations. J. Anat. 95: 345–356, 1961.
 118. Gray, E. G. Electron microscopy of presynaptic organelles of the spinal cord. J. Anat. 97: 101–106, 1963.
 119. Gray, E. G. Are the coats of coated vesicles artifacts?. J. Neurocytol. 1: 363–382, 1972.
 120. Gray, E. G. Presynaptic microtubules and their association with synaptic vesicles. Proc. Roy. Soc. London Ser. B 190: 369–372, 1975.
 121. Gray, E. G. Synaptic fine structure and nuclear, cytoplasmic, and extracellular networks. The stereo frame work concept. J. Neurocytol. 4: 315–339, 1975.
 122. Gray, E. G., and R. W. Guillery. Synaptic morphology in the normal and regenerating nervous system. Intern. Rev. Cytol. 19: 111–182, 1966.
 123. Gray, E.G., and V. P. Whittaker. The isolation of nerve endings from brain: an electron‐microscopic study of cell fragments derived by homogenization and centrifugation. J. Anat. 96: 79–88, 1962.
 124. Gray, E. G., and R. A. Willis. On synaptic vesicles, complex vesicles, and dense projections. Brain Res. 24: 149–168, 1970.
 125. Green, K. Electron microscopic observations on the relationship between synthesis of synaptic vesicles and acetylcholine. Anat. Record 154: 351, 1966.
 126. Greenwalt, J. W., C. S. Rossi, and A. L. Lehninger. Effect of active accumulation of calcium and phosphate ions on the structure of rat liver mitochondria. J. Cell Biol. 23: 21–38, 1964.
 127. Grynszpan‐Winograd, O. Morphological aspects of exocytosis in the adrenal medulla. Phil. Trans. Roy. Soc. London Ser. B 261: 291–292, 1971.
 128. Grynszpan‐Winograd, O. Ultrastructure of the chromaffin cell. In: Handbook of Physiology. Adrenal Gland, edited by H. Blaschko, G. Sayers, and A. D. Smith. Wash. D.C.: Am. Physiol. Soc., 1973, sect. 7, chapt. 21, p. 295–308.
 129. Gurd, J. W., L. R. Jones, H. R. Mahler, and W. J. Moore. Isolation and partial characterization of rat brain synaptic plasma membranes. J. Neurochem. 22: 281–290, 1974.
 130. Hackenbrock, C. R. Energy‐linked ultrastructural transformation in isolated liver mitochondria and mitoplasts. Prevention of configurations by freeze‐cleavage compared to chemical fixation. J. Cell Biol. 53: 450–465, 1972.
 131. Hackenbrock, C. R., and A. I. Caplan. Ion induced ultra‐structural transportations in isolated mitochondria. The energized uptake of calcium. J. Cell Biol. 42: 221–234. 1969.
 132. Hall, C. E., M. A. Jackus, and F. O. Schmitt. The structure of certain muscle fibrils as revealed by the use of electron strains. J. Appl. Physiol. 16: 459–465, 1945.
 133. Hall, Z. W., and R. B. Kelly. Enzymatic detachment of endplate acetylcholine esterase from muscle. Nature New Biol. 232: 62–63, 1971.
 134. Hamberger, A., H. A. Hanson, and J. Sjostrand. Surface structure of nerve terminals during axon regeneration. J. Cell Biol. 47: 319–331, 1970.
 135. Hamilton, R. C., and P. M. Robinson. Disappearance of small vesicles from adrenergic nerve endings in the rat vas deferens caused by red back spider venom. J. Neurocytol. 2: 465–469, 1973.
 136. Hanna, R. B., A. Hirano, and G. D. Pappas. Membrane specializations of dendrite spines and glia in the Weaver mouse cerebellum: a freeze‐fracture study. J. Cell Biol. 68: 403–410, 1976.
 137. Hashimoto, P. H., and S. L. Palay. Peculiar axons with enlarged endings in the nucleus gracilis. Anat. Record 151: 454–455, 1965.
 138. Hernandez‐Nicaise, M. Specialized connections between nerve cells and mesenchymal cells in ctenophores. Nature 217: 1075–1076, 1968.
 139. Heuser, J. E. Evidence of recycling of membrane accompanying transmitter release at the frog neuromuscular junction. Abstr. Soc. Neurosci. Ann. Meeting, 1st, Washington, D.C., 1971.
 140. Heuser, J. E., B. Katz, and R. Miledi. Structural and functional changes of frog neuromuscular junctions in high calcium solutions. Proc. Roy. Soc. London Ser. B 178: 407–415, 1971.
 141. Heuser, J. E., T. S. Reese, and D. M. D. Landis. Preservation of synaptic structure by rapid freezing. In: The Synapse. Cold Spring Harbor Symp. Quant. Biol. XL: 17–24, 1976.
 142. Heuser, J. E., and R. Miledi. Effect of lanthanum ions on function and structure of frog neuromuscular junctions. Proc. Roy. Soc. London Ser. B 179: 247–260, 1971.
 143. Heuser, J. E., and T. S. Reese. Evidence for recycling of synaptic vesicle membrane transmitter release at the frog neuromuscular junction. J. Cell Biol. 57: 315–344, 1973.
 144. Heuser, J. E., T. S. Reese, and D. M. D. Landis. Functional changes in frog neuromuscular junctions studied with freeze‐fracture. J. Neurocytol. 3: 109–131, 1974.
 145. Hirano, H. Ultrastructural study on the morphogenesis of the neuromuscular junction in the skeletal muscle of the chick. Z. Zellforsch. Mikroskop. Anat. 79: 198–208, 1967.
 146. Hokfelt, T., and G. Jonsson. Studies on reaction and binding of monamines after fixation and processing for electron microscopy with special reference to fixation with potassium permanganate. Histochemie 16: 45–67, 1968.
 147. Holtzman, E., A. R. Freeman, and A. Kashner. Stimulation‐dependent alteration in peroxidase uptake at lobster neuromuscular junctions. Science 173: 733–736, 1971.
 148. Horridge, G. A. Non‐motile sensory cilia and neuromuscular junctions in a ctenophore independent effector organ. Proc. Roy. Soc. London Ser. B 162: 333–350, 1965.
 149. Hosie, R. J. A. The localization of adenosine triphosphatases in morphologically characterized subcellular fractions of guinea‐pig brain. Biochem. J. 96: 404–412, 1965.
 150. Hubbard, J. I., and S. Kwanbunbumpen. Evidence for the vesicle hypothesis. J. Physiol. London 194: 407–420, 1968.
 151. Hunt, C. C., and P. G. Nelson. Structural and functional changes in the frog sympathetic ganglion following cutting of the presynaptic nerve fibers. J. Physiol. London 177: 1–20, 1965.
 152. Hurlbut, W. P., and B. Ceccarelli. Transmitter release and recycling of synaptic vesicle membrane at the neuromuscular junction. In: Cytopharmacology of Secretion, Advances in Cytopharmacology, edited by B. Ceccarelli, F. Clementi, and J. Meldolesi. New York: Raven, 1974, vol. 2, p. 141–154.
 153. Jones, S. F., and S. Kwanbunbumpen. The effects of nerve stimulation and hemicholinium on synaptic vesicles at the mammalian neuromuscular junction. J. Physiol. London 207: 31–50, 1970.
 154. Kadota, K., and T. Kadota. Isolation of coated vesicles, plain synaptic vesicles, and flocculent material from a crude synaptosome fraction of guinea pig whole brain. J. Cell Biol. 58: 135–151, 1973.
 155. Kagayoma, M., and W. W. Douglas. Electron microscopic evidence of calcium‐induced exocytosis in mast cells treated with 48/80 or the ionophores A‐23187 and X‐537A. J. Cell Biol. 62: 519–526, 1974.
 156. Kanaseki, T., and K. Kadota. The “vesicle in a basket.” J. Cell Biol. 42: 202–220, 1969.
 157. Katz, B. The transmission of impulses from nerve to muscle, and the subcellular unit of synaptic action. Proc. Roy. Soc. London Ser. B 155: 455–477, 1962.
 158. Katz, B. The Release of Neural Transmitter Substance. Liverpool: Liverpool Univ. Press, 1969.
 159. Katz, B. Quantal mechanism of neural transmitter release. Science 173: 123–126, 1971.
 160. Katz, B., and R. Miledi. The quantal release of transmitter substances. In: Studies in Physiology, edited by J. C. Eccles. New York: Springer Verlag, 1965 p. 118–125.
 161. Kelly, A. M., and S. Zacks. The fine structure of motor endplate morphogenesis. J. Cell Biol. 42: 154–169, 1969.
 162. Kelly, A. M., and S. Zacks. Neuromuscular development in intercostal muscle of the foetal and newborn rat. Neuropathol. Exptl. Neurol. 28: 159, 1969.
 163. Kewar, N., A. Maino, and H. Grundfest. Effect of black widow spider venom on the lobster neuromuscular junction. J. Gen. Physiol. 60: 650–664, 1972.
 164. Koenig, J. Morphogenesis of motor end‐plates in vivo and in vitro. Brain Res. 62: 361–365, 1973.
 165. Korneliussen, H. Elongated profiles of synaptic vesicles in motor endplates. Effects of fixative variations. J. Neurocytol. 1: 279–296, 1972.
 166. Korneliussen, H., and O. Waerhaug. Three morphological types of motor nerve terminals in the rat diaphragm, and their possible innervation of different muscle fiber types. Z. Anat. Entwicklungs. Geschichte 140: 73–84, 1973.
 167. Kristensson, K., and Y. Olsson. Uptake and retrograde axonal transport of peroxidase in hypoglossal neurones. Acta Neuropathol. 19: 1–9, 1971.
 168. Kuffler, S. W., and J. G. Nicholls. The physiology of neurological cells. Ergeb. Physiol. 57: 1–90, 1966.
 169. Kuno, M. Correlation between nerve terminal size and transmitter release. Experientia 27: 1115, 1972.
 170. Lambert, E. H. Defects of neuromuscular transmission in syndromes other than myasthenia gravis. Ann. NY Acad. Sci. 135: 367–384, 1966.
 171. Landis, D. M. D., and T. S. Reese. Differences in membrane structure between excitatory and inhibitory synapses in the cerebellar cortex. J. Comp. Neurol. 155: 93–126, 1974.
 172. Landis, D. M. D., and T. S. Reese. Structure of the Purkinje cell membrane in Staggerer and Weaver mutant mice. J. Comp. Neurol. In press.
 173. Landis, D. M. D., T. S. Reese, and E. Raviola. Differences in membrane structure between excitatory and inhibitory components of the reciprocal synapse in the olfactory bulb. J. Comp. Neurol. 155: 67–92, 1974.
 174. Lang, F., and H. Atwood. Crustacean neuromuscular mechanisms: functional morphology of nerve terminals and the mechanism of facilitation. Am. Zoologist 13: 337–355, 1973.
 175. Lavail, J. H., and M. M. Lavail. The retrograde intraaxonal transport of horseradish peroxidase in the chick visual system: a light and electron microscopic study. J. Comp. Neurol. 157: 303–357, 1973.
 176. Lebeux, Y., and J. Willemot. An ultrastructural study of the microfilaments in rat brain by means of E‐PTA staining and heavy meromysin labelling. II. The Synapses. Cell Tissue Res. 160: 37–68, 1975.
 177. Lee, C. Y., L. F. Tseng, and T. H. Chiu. Influence of denervation on localization of neurotoxins from clapid venoms in rat diaphragm. Nature 215: 1177–1178, 1967.
 178. Lenn, N., and T. S. Reese. The fine structure of nerve endings in the nucleus of the trapezoid body and the ventral cochlear nucleus. Am. J. Anat. 118: 375–389, 1966.
 179. Lentz, T. L. Cytological and cytochemical studies of development of the neuromuscular junction during limb regeneration of the newt (Triturus). J. Cell Biol. 39: 154A–155A, 1968.
 180. Lentz, T. L., J. Rosenthal, and J. E. Mazurkiewicz. Cytochemical localization of acetylcholine receptors by means of peroxidase‐labeled α‐bungarotoxin. Neurosci. Abstr. 1: 627, 1976.
 181. Litchy, W. J. Uptake and retrograde transport of horseradish peroxidase in frog sartorius nerve in vitro. Brain Res. 56: 377–381, 1973.
 182. Manolov, S. Initial changes in the neuromuscular synapses of the denervated rat diaphragm. Brain Res. 65: 303–316, 1974.
 183. Martin, A. R. A further study of the statistical composition of the endplate potential. J. Physiol. London 130: 114–122, 1955.
 184. Matthews, M. R., and V. H. Nelson. Detachment of structurally intact nerve endings from chromatolytic neurons of rat superior cervical ganglion during the depression of synaptic transmission induced by post‐ganglionic axotomy. J. Physiol. London 245: 91–135, 1975.
 185. Mcmahan, U. J. Fine structure of synapses in the dorsal nucleus of the lateral geniculate body of normal and blinded rats. Z. Zellforsch. Mikroskop. Anat. 76: 116–146, 1967.
 186. Mcmahan, U. J., N. S. Spitzer, and K. Peper. Visual identification of nerve terminals in living isolated skeletal muscle. Proc. Roy. Soc. London Ser. B 181: 421–430, 1972.
 187. Mcnutt, N. S., and R. S. Weinstein. Membrane ultra‐structure at mammalian intercellular junctions. Progr. Biophys. Mol. Biol. 26: 45–101, 1973.
 188. Mendolesi, J., J. D. Jameson, and G. E. Palade. Composition of cellular membranes in the pancreas of the guinea pig. J. Cell Biol. 49: 109–158, 1971.
 189. Miledi, R. The acetylcholine sensitivity of frog muscle fibrils after complete or partial denervation. J. Physiol. London 151: 1–23, 1960.
 190. Miledi, R. Properties of regenerating neuromuscular synapses in the frog. J. Physiol. London 154: 190–205, 1960.
 191. Miledi, R., and C. R. Slater. On the degeneration of rat neuromuscular junctions after nerve section. J. Physiol. London 207: 507–528, 1970.
 192. Moor, H., and K. Muhlethaler. Fine structure in frozen‐etched yeast cells. J. Cell Biol. 17: 609–628, 1963.
 193. Moor, H., K. Muhlethaler, H. Waldner, and A. Frey‐Wyssling. A new freezing ultramicrotome. J. Biophys. Biochem. Cytol. 10: 1–13, 1961.
 194. Morgan, I. G., L. S. Wolfe, P. Mandel, and G. Gambos. Isolation of plasma membranes from rat brain. Biochem. Biophys. Acta 241: 737–751, 1971.
 195. Morgan, I. G., J. P. Zanetta, W. C. Breckenridge, G. Vincedon, and G. Gombos. The chemical structure of synaptic membranes. Brain Res. 62: 405–411, 1973.
 196. Morgan, I. G., J. P. Zanetta, W. C. Breckenridge, G. Vincedon, and G. Gombos. Adult rat brain synaptic vesicles; protein and glycoprotein composition. Biochem. Soc. Trans. 2: 249–252, 1974.
 197. Musich, J., and J. I. Hubbard. Release of protein from mouse motor nerve terminals. Nature 237: 279–281, 1972.
 198. Nagasawa, J., W. W. Douglas, and R. A. Schultz. Micropinocytotic origin of coated and smooth microvesicles (“synaptic vesicles”) in neurosecretory terminals of posterior pituitary glands demonstrated by incorporation of horseradish peroxidase. Nature 232: 341–342, 1971.
 199. Nickel, E., and L. T. Potter. Ultrastructure of isolated membranes of Torpedo electric tissue. Brain Res. 57: 508–517, 1973.
 200. Nickel, E., A. Vogel, and P. G. Waser. Coated Vesicles in der Umgebung der neuro‐muskularen Synapsen. Z. Zellforsch. Mikroskop. Anat. 78: 261–266, 1967.
 201. Odor, D. L. Uptake and transfer of particulate matter from the peritoneal cavity of the rat. J. Biophys. Biochem. Cytol. Suppl. 2: 105–108, 1956.
 202. Orci, L., A. Perrelet, and Y. Dunant. A peculiar substructure in the postsynaptic membrane of Torpedo electro‐plax. Proc. Natl. Acad. Sci. US 71: 307–310, 1974.
 203. Orkand, P. M., and E. A. Kravitz. Localization of the sites of α‐aminobutyric and GABA uptake in lobster nerve‐muscle preparations. J. Cell Biol. 49: 75–87, 1971.
 204. Padykula, H. A., and G. F. Gauthier. The ultrastructure of the neuromuscular junctions of mammalian red, white and intermediate skeletal muscle fibers. J. Cell Biol. 46: 27–41, 1970.
 205. Paggi, P., and A. Rossi. Effect of Lactrodectus mactans tredecimguttatus venom on sympathetic ganglion isolated in vitro. Toxican 9: 265–269, 1971.
 206. Palade, G. E. Electron microscopic observation of interneuronal and neuromuscular synapses. Anat. Record 118: 335, 1954.
 207. Palade, G. E. Functional changes in the structure of cell components. In: Subcellular Particles, edited by T. Hayashi. New York: Ronald, 1959, p. 64.
 208. Palade, G. Intracellular aspects of the process of protein synthesis. Science 189: 347–358, 1975.
 209. Palay, S. L. Synapses in the central nervous system. J. Biochem. Biophys. Acta 2: 193–201, 1956.
 210. Palay, S. L. The morphology of synapses in the central nervous system. Exptl. Cell Res. Suppl. 5: 275–293, 1958.
 211. Palay, S. L., and V. Chan‐Palay. Cerebellar Cortex: Cytology and Organization. Berlin: Springer Verlag, 1974.
 212. Palay, S. L., and V. Palay. On the identification of the afferent axon terminals in the nucleus lateralis of the cerebellum. An electron microscope study. Z. Anat. Entwicklungs Geschichte 142: 149–186, 1973.
 213. Pappas, G. D., and S. G. Waxman. Synaptic fine structure‐morphological correlates of chemical and electrotonic transmission. In: Structure and Function of Synapses, edited by G. D. Pappas and D. P. Purpura. New York: Raven, 1972.
 214. Parducz, A., O. Feher, and F. Joo. Effects of stimulation and hemicholinium (HC3) on the fine structure of nerve endings on the superior cervical ganglion of the cat. Brain Res. 34: 61–72, 1971.
 215. Peachey, L. C. Electron microscopic observations on the accumulation of divalent cations in intramitochondrial granules. J. Cell Biol. 20: 95–112, 1964.
 216. Pellegrino De Iraldi, A., and E. De Robertis. Action of reserpine, on the submicroscopic morphology of the pineal gland. Anat. Res. Exptl. 17: 122–123, 1961.
 217. Pellegrino De Iraldi, A., and E. De Robertis. Action of reserpine, iproniazid, and pyrogallol on nerve endings in the pineal gland. Intern. J. Neuropharmacol. 2: 231–239, 1963.
 218. Pellegrino De Iraldi, A., and E. De Robertis. The neurotubular system of the axon and the origin of granulated and non‐granulated vesicles in regenerating nerves. Z. Zellforsch. Mikroskop. Anat. 87: 330–344, 1968.
 219. Peper, K., F. Dryer, C. Sandri, K. Akert, and H. Moor. Structure and ultrastructure of the frog motor endplate. A freeze‐etching study. Cell Tissue Res. 149: 437–453, 1974.
 220. Perri, Y., O. Sacchi, E. Raviola, and G. Raviola. Evaluation of the number and distribution of synaptic vesicles at cholinergic nerve endings after sustained stimulation. Brain Res. 39: 526–529, 1972.
 221. Pfenninger, K. H. The cytochemistry of synaptic densities. II. Proteinaceous components and mechanism of synaptic connectivity. J. Ultrastruct. Res. 35: 451–475, 1971.
 222. Pfenninger, K. H. Synaptic morphology and cytochemistry. Progr. Histochem. Cytochem. 5: 1–86, 1973.
 223. Pfenninger, K., K. Akert, H. Moor, and C. Sandri. Freeze‐etching of presynaptic membranes in the central nervous system. Phil. Trans. Roy. Soc. London Ser. B 261: 387–389, 1971.
 224. Pfenninger, K., K. Akert, H. Moor, and C. Sandri. The fine structure of freeze‐fractured presynaptic membranes. J. Neurocytol. 1: 129–149, 1972.
 225. Pfenninger, K. H., and R. P. Bunge. Freeze‐etching of nerve growth cones and young fibers. A study of developing plasma membranes. J. Cell Biol. 63: 180–196, 1974.
 226. Pfenninger, K. H., and C. M. Rovainen. Stimulation of calcium‐dependence of vesicle attachment sites in the presynaptic membranes. A freeze‐cleave study on the lamprey spinal cord. Brain Res. 72: 1–23, 1974.
 227. Pfenninger, K., C. Sandri, K. Akert, and C. H. Eugster. Contribution to the problem of structural organization of the presynaptic area. Brain Res. 12: 10–18, 1969.
 228. Pinto, J. E. B., R. P. Rothlin, and E. E. Dragnosa. Noradrenaline release by Latrodectus mactans venom in guinea pig atria. Toxicon 12: 385–395, 1974.
 229. Pomerat, C. M., W. J. Hendelman, C. W. Raiborn, and J. F. Massey. Dynamic activities of nervous tissue in vitro. In: The Neuron, edited by H. Hyden. Amsterdam: Elsevier, 1967, p. 119.
 230. Porter, K. R. The submicroscopic structure of animal epidermis. J. Appl. Physics. 24: 1424, 1953.
 231. Price, J. L. The synaptic vesicles of the reciprocal synapse of the olfactory bulb. Brain Res. 11: 697–700, 1968.
 232. Pysh, J. J., and R. G. Wiley. Morphologic alterations of synapses in electrically stimulated superior cervical ganglia of the cat. Science 176: 191–193, 1972.
 233. Pysh, J. J., and R. G. Wiley. Synaptic vesicle depletion and recovery in cat sympathetic ganglia electrically stimulated in vivo. J. Cell Biol. 60: 365–374, 1974.
 234. Quilliam, J. P., and D. L. Tamarind. Some effects of preganglionic nerve stimulation on synaptic vesicle populations in the rat superior cervical ganglion. J. Physiol. London 235: 317–331, 1973.
 235. Raisman, G. Neuronal plasticity in the septal nuclei of the adult rat. Brain Res. 14: 25–48, 1969.
 236. Rall, W., G. Shepherd, T. S. Reese, and M. W. Brightman. Dendrodendritic synaptic pathway for inhibition in the olfactory bulb. Exptl. Neurol. 14: 44–56, 1966.
 237. Rambourg, D. G., and H. L. Koenig. The smooth endoplasmic reticulum; structure and role in the renewal of axonal membrane and synaptic vesicles by fast axonal transport. Brain Res. 93: 1–13, 1975.
 238. Rash, J. E., and M. H. Ellisman. Macromolecular specializations of the neuromuscular junction and the nonjunctional sarcolemma. J. Cell Biol. 63: 567–586, 1974.
 239. Raviola, E., and N. B. Gilula. Intramembrane organization of specialized contacts in the outer plexiform layer of the retina. J. Cell Biol. 65: 192–222, 1975.
 240. Raviola, G., and E. Raviola. Light and electron microscope observations on the inner plexiform layer of the retina. Am. J. Anat. 120: 403–426, 1967.
 241. Rees, R. P., M. B. Bunge, and R. P. Bunge. Morphological changes in the neuritic growth cones and target neuron during synaptic junction development in culture. J. Cell Biol. 68: 240–263, 1976.
 242. Rees, D., and P. N. R. Usherwood. Fine structure of normal and degenerating motor axons and nerve‐muscle synapses in the locust Schistocerca gregaria. Comp. Biochem. Physiol. 43: 83–101, 1972.
 243. Richardson, K. C. The fine structure of autonomic nerve endings in smooth muscle of the rat vas deferens. J. Anat. 96: 427–442, 1962.
 244. Richardson, K. C. Structural and experimental studies on autonomic nerve endings in smooth muscle. Biochem. Pharmacol. 12: 10–11, 1963.
 245. Robertson, J. D. Electron microscopy of the motor endplate and the neuromuscular spindle. Am. J. Phys. Med. 39: 1–43, 1960.
 246. Rosenbluth, J. Substructure of the amphibian motor endplate. J. Cell Biol. 62: 755–766, 1974.
 247. Rosenbluth, J. Synaptic membrane structure in Torpedo electric organ. J. Neurocytol. 4: 697–712, 1975.
 248. Rosenbluth, J., and S. L. Wissig. The distribution of exogenous ferritin in toad spinal ganglia and the mechanism of its uptake by neurons. J. Cell Biol. 23: 307–325, 1964.
 249. Roth, T. F., and K. R. Porter. Yolk protein uptake in the oocyte of the mosquito Aedes aegypti L. J. Cell Biol. 20: 313–332, 1964.
 250. Salpeter, M. M., and M. E. Eldefrawi. Sizes of end plate compartments, densities and acetylcholine receptor and other quantitative aspects of neuromuscular transmission. J. Histochem. Cytochem. 21: 769–778, 1973.
 251. Sandri, C., K. Akert, R. B. Livingston, and H. Moor. Particle aggregations at specialized sites in freeze‐etched postsynaptic membranes. Brain Res. 41: 1–16, 1972.
 252. Santa, T., A. G. Engel, and E. G. Lambert. Histometric study of neuromuscular junction ultrastructure. II. Myasthenia syndrome. Neurology 22: 370–376, 1972.
 253. Schmitt, F. O. Fibrous proteins — neuronal organelles. Proc. Natl. Acad. Sci. US 60: 1092–1101, 1968.
 254. Schueler, F. W. The mechanism of action of the hemicholiniums. Intern. Rev. Neurobiol. 2: 77–97, 1960.
 255. Simonescu, M., N. Simonescu, and G. E. Palade. Morphometry data on the endothelium of blood capillaries. J. Cell Biol. 60: 128–152, 1974.
 256. Singer, S. T., and G. L. Nicolson. The fluid mosaic model of the structure of cell membranes. Science 175: 720–731, 1972.
 257. Sjostrand, F. S. Ultrastructure of retinal rod synapses of the guinea pig eye as revealed by three‐dimensional reconstructions from serial sections. J. Ultrastruct. Res. 2: 122–170, 1958.
 258. Smith, D. S., U. Jarlfors, and R. Beranek. The organization of synaptic axoplasm in the Lamprey (Petromyzon marinus) central nervous system. J. Cell Biol. 46: 199–219, 1970.
 259. Smith, J. M., J. L. O'Leary, A. B. Harris, and A. J. Gray. Ultrastructural features of the lateral geniculate nucleus of the cat. J. Comp. Neurol. 123: 357–378, 1965.
 260. Smith, C. A., and F. S. Sjostrand. Structure of the nerve endings on the external hair cells of the guinea pig cochlea as studied by serial sections. J. Ultrastruct. Res. 5: 523–556, 1961.
 261. Smith, C. A., and F. S. Sjostrand. A synaptic structure in the hair cells of the guinea pig cochlea. J. Ultrastruct. Res. 5: 185–192, 1961.
 262. Sotelo, C., and S. L. Palay. Altered axons and axon terminals in the lateral vestibular nucleus of the rat. Possible example of axonal remodeling. Lab. Invest. 25: 653–671, 1971.
 263. Streit, P., K. Akert, O. Sandri, R. P. Livington, and H. Moor. Dynamic ultrastructure of presynaptic membranes at nerve terminals in the spinal cord of rats. Anesthetized and unanesthetized preparations compared. Brain Res. 48: 11–26, 1972.
 264. Takeuchi, A. The long lasting depression in neuromuscular transmission of frog. Japan. J. Physiol. 8: 102–113, 1958.
 265. Taxi, J. Etude de l'ultrastructure des zones synaptiques dans les ganglions sympathiques de la grenouille. Compt. Rend. 252: 174–176, 1961.
 266. Teichberg, S., E. Holtzman, S. M. Crain, and R. R. Peterson. Circulation and turnover of synaptic vesicle membrane in cultured fetal mammalian spinal cord neurons. J. Cell Biol. 67: 215–230, 1976.
 267. Teravainen, H. Development of the myoneural junction in the rat. Z. Zellforsch. Mikroskop. Anat. 87: 249–265, 1968.
 268. Thesleff, S. Effects of the motor innervation on the chemical sensitivity of skeletal muscle. Physiol. Rev. 40: 734–752, 1960.
 269. Tilney, G., and K. R. Porter. Studies on the microtubules in heliozoa. II. J. Cell Biol. 34: 327–343, 1967.
 270. Tranzer, J. P., and H. Thoenen. Electronmicroscopic localization of 5‐hydroxydopamine (3,4,5‐trihydroxy‐phenylethylamine), a new “false” sympathetic transmitter. Experientia 23: 743–745, 1967.
 271. Turner, P. T., and A. B. Harris. Ultrastructure of exogenous peroxidase cerebral cortex. Brain Res. 74: 305–326, 1974.
 272. Uchizono, K. Characteristics of excitatory and inhibitory synapses in the central nervous system of the cat. Nature 207: 642–643, 1965.
 273. Uchizono, K. Inhibitory synapses on the stretch receptor neurone of the crayfish. Nature 214: 833–834, 1967.
 274. Ukena, T. E., and R. D. Berlin. Effect of colchicine and vinblastine on the topographical separation of membrane functions. J. Exptl. Med. 136: 1–7, 1972.
 275. Usherwood, P. N. R. Release of transmitter from degenerating locust motorneurons. J. Exptl. Biol. 59: 1–16, 1973.
 276. Usherwood, P. N. R., D. G. Cochrane, and D. Rees. Changes in structural physiological, and pharmacological properties of insect excitatory nerve‐muscle synapses after motor nerve section. Nature 218: 589–591, 1968.
 277. Valdivia, O. Methods of fixation and the morphology of synaptic vesicles. J. Comp. Neurol. 142: 257–274, 1971.
 278. Van Der Loos, H. Fine structure of synapses in the cerebral cortex. Z. Zellforsch. Mikroskop. Anat. 60: 815–825, 1963.
 279. Van Orden, L. S., K. G. Bensch, and N. J. Giarman. Histochemical and functional relationships of catecholamines in adrenergic nerve endings. II. Extravesicular norepinephrine. J. Pharm. Exptl. Therap. 155: 428–439, 1967.
 280. Van Orden, L. S., F. E. Bloom, K. G. Bench, and N. J. Giarman. Histochemical and functional relationships of catecholamines in adrenergic nerve endings. I. Participation of granular vesicles. J. Pharm. Exptl. Therap. 154: 185–199, 1966.
 281. vom Hungen, K., H. R. Mahler, and W. T. Moore. Turnover of protein and ribonucleic acid in synaptic subcellular fractions from rat brain. J. Biol. Chem. 243: 1415–1423, 1968.
 282. Walberg, F. The early changes in degeneration boutons and the problem of argyrophilia. Light and electron microscopic observations. J. Comp. Neurol. 122: 113–137, 1964.
 283. Walberg, F. Further electron microscopical investigations of the inferior olive of the cat. In: Progress in Brain Research. Topics in Basic Neurology, edited by W. Bargmann and J. P. Schade. Amsterdam: Elsevier, 1964, vol. 6, p. 59.
 284. Waxman, S. G., and G. D. Pappas. Pinocytosis at postsynaptic membranes: electron microscopic evidence. Brain Res. 14: 240–244, 1969.
 285. Weinshilbaum, R. M., N. B. Thoa, D. B. Johnson, J. Kopin, and J. Axelrod. Proportional release of norepinephrine and dopamine‐β‐hydroxylase from sympathetic nerves. Science 174: 1349–1351, 1972.
 286. Weldon, P. R. Pinocytotic uptake and intracellular distribution of colloidal thorium dioxide by cultured sensory neuntes. J. Neurocytol. 4: 341–356, 1975.
 287. Westrum, L. E. On the origin of synaptic vesicles in cerebral cortex. J. Physiol. London 179: 48–69, 1965.
 288. Whittaker, V. P., W. B. Essman, and G. H. C. Dowe. The isolation of pure cholinergic synaptic vesicles from the electric organs of Elasmobranch fish of the family Torpedinidae. Biochem. J. 128: 833–846, 1972.
 289. Windle, W. F. Regeneration of axons in the vertebrate central nervous system. Physiol. Rev. 36: 427–440, 1956.
 290. Wolfe, D. E., L. T. Potter, K. C. Richardson, and J. Axelrod. Localizing tritiated norepinephrine in sympathetic axons by electron microscopic autoradiography. Science 138: 440–442, 1962.
 291. Yamada, K. M., B. S. Spooner, and N. K. Wessells. Ultrastructure and function of growth cones and axons of cultured nerve cells.
 292. Yamamura, H. I., and S. H. Snyder. High affinity transport of choline into synaptosomes of rat brain. J. Neurochem. 21: 1355–1374, 1973.
 293. Zachs, S. I., and A. Saito. Uptake of exogenous horseradish peroxidase by coated vesicles in mouse neuromuscular junctions. J. Histochem. Cytochem. 17: 161–167, 1969.

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Structure of the Synapse
 

How to Cite

J. E. Heuser, T. S. Reese. Structure of the Synapse. Compr Physiol 2011, Supplement 1: Handbook of Physiology, The Nervous System, Cellular Biology of Neurons: 261-294. First published in print 1977. doi: 10.1002/cphy.cp010108