Comprehensive Physiology Wiley Online Library

Structure of the Synapse

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. and . 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
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. . 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. and . 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


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. . 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.

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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