Ultrastructure Of Synapses Research Articles

Ultrastructure of synapses in the first-evolved nervous systems.

The phylum Cnidaria represents the first group of animals to evolve a recognizable nervous system. A comparison of the ultrastructural features of synaptic loci in animals representing all four classes of the cnidaria has provided an overview of the first-evolved synapses that can be compared morphologically to synapses in higher forms. Synapses in these watery jellylike animals with unmyelinated axons are sparse and difficult to fix well. However, we now have sufficient evidence to define an early synapse as one with paired electron dense plasma membranes separated by a 13-25 nm gap containing intracleft filaments and with vesicles on one or both sides of the synaptic cleft. The vesicles are of three types: dense-cored, clear, and opaque. Neuromuscular synapses resemble neuronal synapses and lack the postsynaptic specializations of higher animals. However, some coelenterates, such as the jellyfish Chrysaora, have a postsynaptic cisterna in the muscle. Neuromuscular and neuronematocyte synapses can have either clear or dense-cored vesicles. Opaque vesicles at two-way interneuronal synapses and at neuromuscular synapses in the oral sphincter muscle of sea anemones can be labelled with antisera to the neuropeptides Antho-RFamide (Antho-Arg-Phe-NH2) and Antho-RWamides (Antho-Arg-Trp-NH2) I and II, respectively. That suggests that neuropeptides evolved as neurotransmitters early in the animal kingdom. The basic differences between first evolved synapses and synapses of higher animals are the lack of postjunctional folds at neuromuscular synapses and the presence of fewer and somewhat larger synaptic vesicles, generally containing granular cores, in the more primitive animals.

Ultrastructure of synapses from the pretectum in the A‐laminae of the cat's lateral geniculate nucleus

We have recently shown in cats that many neurons projecting to the lateral geniculate nucleus from the pretectum use gamma-amino butyric acid (GABA) as their neurotransmitter. We sought to determine the morphology of synaptic terminals and synapses formed by these pretectal axons and the extent to which they resemble other GABAergic terminals found in the geniculate neuropil (i.e., from geniculate interneurons and cells of the nearby perigeniculate nucleus). To do this, we labeled a population of pretectal axons with the anterograde tracer Phaseolus vulgaris leucoagglutinin and analyzed the morphology and synaptology of labeled pretectal terminals in the A-laminae of the cat's lateral geniculate nucleus. The pretectal projection, which arises primarily from the nucleus of the optic tract (NOT), provides synaptic innervation to elements in the geniculate neuropil. The labeled NOT terminals are densely packed with vesicles, contain dark mitochondria, and form symmetrical synaptic contacts. These are characteristics of the F1 type of terminal, and we know from other studies that GABAergic axon terminals from interneurons and perigeniculate cells also give rise to F1 terminals. We compared our population of NOT terminals with labeled perigeniculate and unlabeled F1 terminals selected from the geniculate neuropil and found that all three populations share many morphological characteristics. Both qualitative and quantitative assessments of the pretectal terminals suggest that these are a type of F1 terminal. Most pretectal terminals selectively form synapses onto geniculate profiles that contain irregularly distributed vesicles and dark mitochondria and that are postsynaptic to other types of terminals. These postsynaptic targets thus exhibit features of another class of inhibitory, GABAergic terminal known as F2 terminals, which are the specialized appendages of geniculate interneurons. Pretectal inputs, being GABAergic, may thus serve to inhibit local interneuronal outputs. Pretectal axons also innervate the perigeniculate nucleus, in which the only targets are the other main type of inhibitory, GABAergic neurons. These results suggest that the pretectum may facilitate retinal transmission through the lateral geniculate nucleus by providing inhibition to the local inhibitory cells: the interneurons and probably perigeniculate cells. This would serve to release geniculate relay cells from inhibition.

Distribution of synapses on two types of ascending interneurons in the crayfish, Procambarus clarkii

About 60 pairs of ascending interneurons are present in the terminal ganglion of the crayfish Procambarus clarkii (Girard). Some of these interneurons have been impaled intracellularly, characterized physiologically, and then labeled with horseradish peroxidase (HRP) to examine the distribution and ultrastructure of synapses. A close relationship between ultrastructure and physiological properties has been found between two types of interneurons, which either have a pre-motor effect upon motor neurons or have no such effect. In one interneuron with a pre-motor effect (6D2), input and output synapses are intermingled on thicker branches, whereas only input synapses are found on small diameter branches. Only input synapses have been observed on the branches in another interneuron with-out a pre-motor effect (6B1). No differences in branch morphology are found in these two interneurons. Interneuron 6D2 contains large numbers of small round agranular vesicles, but the same type of synaptic vesicles is rarely seen in interneuron 6B1, which has no output synapses. Our results indicate a good correlation between the synaptic distribution and pre-motor effects of interneurons in the terminal ganglion.

Ultrastructure of synapses and golgi analysis of neurons in neocortex of the lateral gyrus (visual cortex) of the dolphin and pilot whale

Qualitative and computerized quantitative analyses of ultrastructural features of synapses in different layers of the primary visual cortex in the dolphin (Stenella coeruleoalba) and the pilot whale (Globicephala melaena) were carried out. Also, Golgi and cytoarchitectonic analyses were performed in the same species of cetaceans and, additionally, in Tursiops truncatus and Phocaena phocaena. It was found that on a synaptic level, as well as in cytoarchitectonic and Golgi features, the neocortex of cetaceans combines evolutionary progressive features and conservative features with a marked prevalence of the latter. Thus, the total number of synapses in visual neocortex in cetaceans is closer to this value in higher Primates. On the other hand, the laminar density of synapses per mm3 is generally the same in all layers in cetacean visual cortex and numerically is close to values found in small lissencephalic brains. Also, the synapse/neuron ratio in the dolphin visual cortex is of the same order as in cortices of rodents and lagomorphs and much higher than in cortices of advanced terrestrial mammals. Layers I and II contain approximately 70% of the total synapses in the cortical slab through visual cortex. Layer I also contains the extraverted dendrites of neurons of layer II and thus these two layers resemble a paleoarchicortical type of organization superimposed on a more typical neocortical organization of the lower cortical layers. In this respect the convexity neocortex of cetaceans is generally similar to the neocortices of phylogenetically ancient extant mammals such as basal Insectivora and Chiroptera.

Morphology of synapses in the autonomic nervous system.

The ultrastructure of synapses in the autonomic nervous system is reviewed. The synaptic organization of the parasympathetic ganglia is relatively simple. Preganglionic axons form synapses either on the soma or on short perikaryal processes of the ganglionic neurons. The presynaptic terminals have a cholinergic morphology and contain mainly small clear vesicles with a few large dense cored vesicles. A few neuropeptides have been localized to the large dense cored vesicles of these terminals. The postganglionic parasympathetic axons ramify within their target tissues where they form close associations, but not true synaptic contacts. Sites of release of transmitter are recognized morphologically as varicosities along the length of the axon that contain clusters of small clear vesicles with a few large dense cored vesicles. The organization of the sympathetic nervous system is somewhat more complex. In addition to acetylcholine, enkephalin also exists in these terminals, probably in the large dense cored vesicles. There are at least three types of ganglion cell neurons in the paravertebral portion of the sympathetic nervous system: those that contain norepinephrine alone, those that contain norepinephrine along with neuropeptide Y, and those that contain acetylcholine and vasoactive intestinal polypeptide. The first type provides innervation to the parenchyma of the target tissues, while the second mainly innervates blood vessels. The third type innervates the sweat glands. In the prevertebral ganglia, a fourth type of neuron exists that contains norepinephrine and somatostatin. This neuron probably innervates the gut. Preganglionic terminals of the cholinergic type form synaptic connections mainly with the dendrites of the sympathetic ganglion neurons. In addition to the types of synapses described for the paravertebral ganglia, neurons in the prevertebral ganglia receive synaptic connections from dorsal root ganglia and from the enteric nervous system. The sympathetic ganglia also contain interneurons that receive preganglionic synapses and form efferent synapses with some of the principal ganglion cells. The interneurons have been shown to contain a variety of transmitters, including norepinephrine, epinephrine, dopamine, serotonin, and a number of neuropeptides. The postganglionic sympathetic axons have a similar morphology to the parasympathetic axons. They form networks in their targets, and the axons display varicosities with concentrations of both small and large vesicles. After appropriate fixation, these vesicles are seen to possess dense cores.(ABSTRACT TRUNCATED AT 400 WORDS)

Ultrastructure of synapses in the cerebellar cortex after long-term activation of climbing fibres

Adult male rats were treated for 24 or 48 h with harmaline which selectively activates neurones in the inferior olivary nucleus which give rise to climbing fibres projecting to the cerebellar vermis. Electrophysiological studies have shown that harmaline-induced climbing fibre activity completely blocks the responses of the Purkinje cell to parallel fibre input. Morphometric analysis of the ultrastructure of climbing and parallel fibre synapses revealed no significant differences in morphology between vermis (experimental) and hemisphere (control). These findings indicate that the decreased responsiveness of Purkinje cells to parallel fibre inputs induced by increased climbing fibre activity over 24 or 48 h is not accompanied by any observable structural changes in the cerebellar cortex.

Ultrastructure of synapses from the A-laminae of the lateral geniculate nucleus in layer IV of the cat striate cortex.

The morphology of synapses in layer IV of the cat striate cortex was studied by electron microscope (EM) autoradiography of serial sections following injection of tritiated amino acids into the lateral geniculate nucleus. Of the terminals in the neuropil, 22% had 2 or more silver grains in 10 successive sections and were labeled at 8-80 times the background level. These terminals were considered to be specifically labeled and to be derived from the lateral geniculate. Two forms of geniculate synapse were observed. One had medium-size, round vesicles and a modest postsynaptic asymmetry (RA); the other had smaller, pleomorphic vesicles and hardly any postsynaptic opacity; that is, it appeared symmetrical (PS). The geniculate RA terminals were presynaptic to dendritic spines, fine processes, and cell bodies; the geniculate PS terminals were presynaptic to dendrites and cell bodies but not to spines. The possible sources of geniculate PS terminals are discussed.

Changes in synaptic morphology associated with presynaptic and postsynaptic activity: an in vitro study of the electrosensory organ of the thornback ray.

The influence of synaptic activity on synaptic structure was studied by selectively stimulating the presynaptic or postsynaptic membranes of ribbon synapses in an in vitro preparation, and examining the ultrastructure of synapses with conventional electron microscopic methods. Functionally significant changes in synaptic morphology were observed after direct depolarization of the presynaptic membrane or incubation with the neurotransmitter glutamate to depolarize the postsynaptic membrane. After depolarizing the presynaptic membrane for 30 seconds, the depth of the postsynaptic trough was reduced, and other morphological changes correlated with decreased sensitivity and spontaneous activity were evident. Depolarizing the postsynaptic membrane by incubating synapses with the neurotransmitter glutamate, produced opposite effects. These results suggest that synapses can undergo functionally significant morphological changes in response to certain patterns of activity. The mechanism for these changes might include synaptic vesicle recycling processes, changes in ion concentration, or cytoskeletal alterations in the presynaptic, postsynaptic, or support cells. These mechanisms could operate in association with long-term changes in synaptic efficacy or account for some physiological phenomena such as synaptic fatigue or accommodation.

Distribution and ultrastructure of synapses on a premotor local nonspiking interneuron of the crayfish.

Many premotor local nonspiking interneurons are involved in the control of the uropod movements of a crayfish. One of these interneurons was impaled intracellularly, characterized physiologically, and then labeled by intracellular horseradish peroxidase (HRP) injection to examine the distribution and ultrastructure of synapses. Depolarization of this interneuron by a current injection excited the closer motoneurons of the uropod and inhibited its opener motoneurons, but hyperpolarization had no effect. Input and output synapses are distributed all over the major branches and the finer neurites except for the main neurite (7-10 micron in diameter), which runs near the dorsal surface of the neuropil. Both types of synapse are located on the same neurite and are often intermingled in close proximity, often less than 1 micron apart. Presynaptic terminals of the interneuron contain round, clear vesicles that are densely packed in fine branches and spines. The number of synaptic vesicles associated with a particular output synapse was estimated to be about 2,000. No dense-cored granules are observed in the labeled neurites. Our results support the proposal that synaptic transmission in this class of interneurons of the crayfish can sometimes be restricted to a very small region of the branches and that, therefore, different regions of the interneuron can function independently.

Ultrastructure of synapses with different transmitter-releasing characteristics on motor axon terminals of a crab, Hyas areneas.

Synaptic terminals on branches of an excitatory motor axon in a spider crab (Hyas areneas) were examined by electron microscopy to determine whether differences in size, structure, and number of synapses could be correlated with differences in transmitter release. Terminals releasing relatively large amounts of transmitter during low frequencies of nerve impulses ("high-output" terminals) had larger synapses, more prominent presynaptic dense bodies (active zones), and fewer synapses per unit length than terminals releasing relatively small amounts of transmitter ("low-output" terminals). Neither the difference in synaptic area, nor the quantitative differences in the active zones, were sufficient in themselves to explain the difference in synaptic efficacy, and it is postulated that a non-linear relationship may exist between structural features of the synapse and release of transmitter by a nerve impulse, and that differences other than those apparent from the ultrastructure could be involved. Greater facilitation at low-output terminals with high frequencies of nerve impulses may be due to greater reserves of "immediately available" transmitter, and to recruitment or activation of more individual synaptic contacts.

An analysis of the association between various synaptic parameters during cortical development

The ultrastructure of synapses from the molecular layer of parietal cortex was examined in male rats aged between 7 and 75 days postnatal. Two groups were compared, one consisting of rats anaesthetized with 50mg/kg pentobarbitone, and the other of rats killed by stunning across the back of the neck. Synaptic parameters were measured on electron micrographs, and the interrelationships of various parameters were analyzed during synaptogenesis and comparing anaesthetized and unanaesthetized material. Terminal area was greatest in positively-curved synapses in anaesthetized and unanaesthetized terminals at all age groups, although unanaesthetized terminals had smaller areas overall for the same range of curvatures. Synaptic vesicle density was either constant over the range of synaptic curvatures, or was lower in negatively-curved than in positively-curved terminals. The latter trend was especially marked in the 7-, 21- and 75-day unanaesthetized terminals. When synaptic length was plotted against synaptic curvature, the highly curved junctions were frequently the shortest. Synaptic vesicle numbers increased as the terminal area increased while, for any given terminal area, there were more vesicles in older than in younger terminals and also in the larger unanaesthetized terminals. No clear trends emerged from the relationship between synaptic vesicle density and synaptic length.

Ultrastructure of synapses in the lateral line canal organ.

The ultrastructure of afferent and efferent synapses on hair cells in the lateral line canal organ of hair cells in the lateral line canal organ of the fish Lota lota was studied, utilizing various fixation and staining techniques. New information was obtained about membrane-associated material, such as the presynaptic body and postsynaptic densities, by examining glutaral-dehyde-fixed material not subjected to osmication. Contrast was instead obtained either by section staining with uranyl acetate and lead citrate or by block impregnation with phosphotungstic acid (PTA). PTA-staining enhances the postsynaptic membrane of both the afferent and efferent synapses. It also stains the presynaptic dense projections at the efferent synapse and in a differential fashion, the afferent synaptic body. Secretion staining reveals a substructure in the feed of the afferent synaptic body, faintly seen but masked in osmicated tissue.

Ultrastructure of synapses and cellular relationships in the oculomotor nucleus of the rhesus monkey.

The fine structure of synapses and of cellular relations was examined in the somatic efferent portion of the oculomotor nucleus of the adult rhesus monkey. Axosomatic and axodendritic synapses are characterized by distinct synaptic clefts which usually measure 20-30 nm between pre- and postsynaptic membranes. Cytoplasmic "thickenings" of pre- and postsynaptic membranes are often observed. Subjunctional bodies are present at both axosomatic and axodendritic synapses. Somatic and dendritic spine synapses are present. Serial synapses are also found, suggesting the operation of presynaptic inhibition in this nucleus. At some synapses the extracellular gap between pre- and postsynpatic membranes is reduced to 5-9 nm. However, junctions similar to the latter are also present between neurons and glia, and at the junctions between adjacent glial elements. The present results provide no evidence for a clear morphological substrate for electrotonic transmission in the somatic efferent portion of the primate oculomotor nucleus.

Ultrastructural effects of 4-aminopyridine on the presynaptic membrane in the rat spinal cord

The effects of 4-aminopyridine (4-AP, 1 mg/kg, i.v.) on the ultrastructure of synapses in the ventral horn of the spinal cord were examined in rats anesthetized with 50 and 100 mg/kg, i.p., pentobarbital sodium and alpha-chloralose respectively. The presynaptic membrane of the 4-AP-treated animals, in both S- and F-type synapses, was wrinkled and gave frequently rise to omega-shaped profiles. However, it was not prominently lifted in comparison with the controls. In both extracellular (EF) and protoplasmic fracture faces (PF) of freeze-etched replicas, the frequency of the presynaptic membrane modulations (PMM) per unit area rose significantly under the influence of 4-AP. The ratio of open (crater-like) to total PMM in EF increased almost twice under the experimental condition. No differential 4-AP effects were seen between pentobarbital- and chloralose-treated animals. The morphological evidence is consistent with electrophysiological data showing that 4-AP facilitates the transmitter release at synaptic endings.

Changes in ultrastructural synaptoarchitectonics caused by endotoxin

The authors studied the ultrastructure of synapses of the dog sensory-motor cortex in response to intravenous injection of typhoid endotoxin. The most pronounced shifts were noted in the dendrite neuron apparatus. Activation in the cortical structures was connected with an increase in the number of functioning synapses and reconstruction of interneuronal connections. There was an increase in the length of the contacting membranes, and of the quantity of synaptic vesicles; the content of dense core vesicles is released. Depression is associated with dystrophic changes in the synapses.

An ultrastructural study into the effects of pentobarbitone on synaptic organization

A series of adult male rats was analyzed to test the effects of varying doses of pentobarbitone sodium on the ultrastructure of synapses in the molecular layer of the parietal cortex. The rats were divided into the following categories: unanaesthetized stunned, unanaesthetized cannulated and those subjected to 40, 80, 160, 300, or 400 mg/kg pentobarbitone. All material was examined both qualitatively and quantitatively after aldehyde-OsO4 or ethanolic phosphotungstic acid (E-PTA) treatment. The principal qualitative observations were: the preponderance in the unanaesthetized stunned and 160-400 mg/kg material of a variety of intraterminal profiles including synaptic vesicles, mitochondria, coated vesicles, tubular profiles, vacuoles, cisterns and double membrane profiles; the presence of exocytotic sites along the presynaptic membrane in the unanaesthetized stunned and cannulated material; the presence of endocytotic sites over the limiting membrane of the terminal away from the cleft in the unanaesthetized stunned and 160-400 mg/kg material; the prominence of the presynaptic network in the unanaesthetized and 40 mg/kg E-PTA material; discontinuity of the cleft material in the 40-160 mg/kg material. Findings to emerge from the quantitative aspect of the study show that pentobarbitone influences synaptic curvature, with a marked increase in curvature negativity over the 0-80 mg/kg dose range and a decrease in negativity at higher dose levels. The increase in curvature negativity is accompanied by an increase in synaptic length and dense projection numbers, with a consonant increase in the perimeter and area of the presynaptic terminal. Reversal of the negativity trend at higher dose levels is parallelled by reversal of these accompanying trends. Both sets of findings can be accounted for by membrane recycling within the terminal, supporting a membrane redistribution hypothesis.

The nervous system of ctenophores. III. Ultrastructure of synapses.

The ultrastructure of synapses from the nervous systems of seven species of ctenophores has been studied. All synaptic contacts so far observed show a peculiar organization characteristic of this phylum: the pre-synaptic neurite contains in sequence from the plasma membrane: a row of vesicles lining the synaptic membrane, a sac of endoplasmic reticulum which is connected with the rough reticulum of the neuron, and one or several mitochondria. The arrangement of these closely associated organelles is constant, forming a complex referred to as thepre-synaptic triad. The pre-synaptic triad is found both in interneural synapses—which may be polarized, symmetrical or reciprocal — and in various neuro-receptor and neuro-effector junctions. The possible functional implications of these features are discussed.

The ultrastructure of giant fibre and serial synapses in crayfish.

The ultrastructure of synapses between the cord giant fibres (lateral and medial) and the motor giant fibres in crayfish, Astacus pallipes, third abdominal ganglia have been examined. These electrotonic synapses are asymmetrical, they have synaptic vesicles only in the presynaptic fibre, and they have synaptic cleft widths normally of about 100 A but narrowed to about 50 A in restricted areas. Localized increases in density of the synaptic cleft and adjacent membranes also occur within a synapse, and synaptic vesicles are most tightly grouped at the membrane in such areas. Tight or gap junctions with 30 A or narrower widths have not been found, but the junctions probably function in a similar way to gap junctions.

Effect of direct electrical stimulation on synapse ultrastructure in the cerebral cortex

Effect of direct electrical stimulation on synapse ultrastructure in the cerebral cortex

Synapses on neurosecretory cells of the supra-optic nucleus in white mice.

FEW observations have been reported on the ultrastructure of synapses between nerve fibres and the perikarya of neurosecretory cells. Electron microscope observations on synapses on perikarya and on branches of neurosecretory cells of the pre-optic nucleus in teleosts—perch and trout—have been published1,2, and recently short preliminary reports on the ultrastructure of synapses on cells of the supra-optic nucleus of white mice3 and rats4 have appeared. Further details of synapses on the neurosecretory cells of the supra-optic nucleus of white mice are reported here.