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At least 19 recordsLinked to original sources
PubMed1991

Selective localization of polyribosomes beneath developing synapses: a quantitative analysis of the relationships between polyribosomes and developing synapses in the hippocampus and dentate gyrus.

Previous studies have revealed that polyribosomes are selectively localized beneath post-synaptic sites on central nervous system (CNS) neurons, and are particularly prominent during periods of synapse growth. The present study evaluates whether polyribosomes are most prominent at a consistent time in the developmental history of the synapse, or instead at a consistent time in the life of the organism regardless of the state of synaptic maturation (suggesting a globally acting factor). We compare the time course of synaptogenesis and the association between polyribosomes and developing synapses in three regions that develop at different rates: the external and internal blades of the dentate gyrus, and the CA1 region of the hippocampus proper. Each region was examined electron microscopically at 1, 4, 7, 10, 15, 20, 28 and over 120 days of age, evaluating: (1) synapse density (the number of synaptic profiles/area of neuropil), (2) the width of the neuropil layers, (3) the proportion of synapses with underlying polyribosomes, and (4) the number of polyribosome-containing synapses/area of neuropil. As anticipated on the basis of the differences in cytogenesis, the time course of synaptogenesis was different in the three regions. In the external blade of the dentate gyrus, synapse density increased in a nearly linear fashion between birth and 15 days of age, and then continued to increase at a somewhat slower rate until 28 days of age. Synapse development in the internal blade was delayed by several days in comparison to the external blade. In CA1, synapse density increased slowly between 1 and 7 days, and then at a rapid rate between 7 and 28 days of age. In all three regions, the proportion of synapses with underlying polyribosomes was highest between 1 and 7 days of age, and then decreased as synapse density increased. However, the peak in the number of polyribosome-containing synapses/unit area of neuropil occurred at different times in the three regions (4-7 days of age in the external blade of the dentate gyrus and in CA1, and 20 days of age in the internal blade). In addition to further defining the relationship between polyribosomes and developing synapses, the present study provides a data base on the time course of synapse development in the hippocampus and dentate gyrus, which will be useful for comparisons with other measures.

Aging↗
PubMed1977

Synapse turnover: the formation and termination of transient synapses.

Neurons dissociated from chick embryo retina form synapses with cultured rat striated muscle cells in 35-90 min when neurite extension is uncoupled from later steps in synapse formation. The results suggest that a reaction is required for synapse formation after neurons adhere to muscle cells. All synapses between retina neurons and muscle cells are terminated in 3-10 days depending on the developmental age of the neurons. The half-lives of synapses between muscle cells and retina neurons from 8-, 12-, or 13-day embryos are 36, 26, and 5 hr and mean synapse life-times are 53, 37, and 7.1 hr, respectively. The results show that synapses turn over and that the rate of turnover increases during development. The results suggest that both synapse formation and termination rates are regulated and that the specificity of synaptic connections can be increased by selective termination of synapses.

Animals↗
PubMed1990

Synapsins in the vertebrate retina: absence from ribbon synapses and heterogeneous distribution among conventional synapses.

The vertebrate retina contains two ultrastructurally distinct types of vesicle-containing synapses: conventional synapses, made predominantly by amacrine cells, and ribbon synapses, formed by photoreceptor and bipolar cells. To identify molecular differences between these synapse types, we have compared the distribution of the synapsins, a family of nerve terminal phosphoproteins, with that of synaptophysin (p38) and SV2, two intrinsic membrane proteins of synaptic vesicles. We report an absence of synapsin I and II immunoreactivity from all ribbon-containing nerve terminals. These include terminals of rod cells in developing and adult rat retina, rod and cone cells in monkey and salamander retinas, and rat bipolar cells. Furthermore, we show that synapsins I and II are differentially distributed among conventional synapses of amacrine cells. The absence of the synapsins from ribbon synapses suggests that vesicle clustering and mobilization in these terminals differ from that in conventional synapses.

Aging↗
PubMed1992

Morphological comparison by scanning electron microscopy of transient retina-muscle synapses and long-lived spinal cord-muscle synapses.

Retinal neurons will form cholinergic synapses on muscle cells in tissue culture, however, these inappropriate synapses are transient. Although within 24 hrs. myotubes are readily innervated, by 7 days of coculture no physiological response can be detected. In contrast, spinal cord neurons form long-lived synapses on muscle cells which can be detected for several weeks. In this study, we examined retina-muscle and spinal cord-muscle cocultures to determine whether retinal neurons withdrew their processes from muscle cells, and preferentially maintained contacts on other retinal neurons. Using scanning electron microscopy, we observed that during the first 24 hrs. of coculture both types of neurons extend processes along myotubes. The neurite outgrowth occurs concomitantly with the observed increase in physiologically detected synaptic muscle responses. Over the next 6 days, retinal neurite contacts on the muscle cells are withdrawn, while spinal cord contacts remain. Retinal neurons remain in contact with other retinal neurons at day 7 of coculture. Thus, retinal neurons form and maintain synapses on their appropriate target (other retinal neurons); whereas, they withdraw contacts from inappropriate targets (muscle cells). By contrasting retinal and spinal cord synapses on muscle cells, we hope to elucidate the mechanisms of synaptic recognition and maintenance.

Animals↗
PubMed1989

Normal numbers of retinotectal synapses during the activity-sensitive period of optic regeneration in goldfish: HRP-EM evidence implicating synapse rearrangement and collateral elimination during map refinement.

Optic and nonoptic fibers and synapses were counted in the primary optic innervation layer (S-SO-SFGS) in anteromedial tectum in normal goldfish and in fish 30, 60, and 240 d after the optic nerve was crushed. A newly developed "cold-fill" HRP-labeling protocol was used to label optic afferents for electron microscopy, and counts were then made on EM photomontages of columns through the HRP-labeled S-SO-SFGS. Normal numbers of retinotectal synapses were present at 30 d regeneration, at a time when activity-dependent refinement of the optic projection is incomplete. Normal numbers were also found at 60 and 240 d, when refinement is largely completed. In contrast to this constancy in optic synapse numbers, there was nearly 10 times the normal number of optic fibers in the SFGS at 30 d, and these were reduced by 50% at 60 d, remaining over 4 times normal at 240 d. These findings imply extensive rearrangement of optic synapses during map refinement. They also indicate that synapse rearrangement is associated with the elimination of optic collaterals.

Animals↗
PubMed1989

Commissural synapses, but not mossy fiber synapses, in hippocampal field CA3 exhibit associative long-term potentiation and depression.

When CA3 commissural afferents received low-frequency (weak) stimuli synchronized with a train of mossy fiber bursts (strong), associative long-term potentiation (LTP) was induced at mixed commissural and associational synapses on hippocampal CA3 pyramidal cells in vitro. In contrast, a weak mossy fiber input did not potentiate when given in phase with commissural/associational bursts. Furthermore, commissural/associational synapses receiving low-frequency stimuli out-of-phase with strong rhythmic mossy fiber input showed associative long-term depression (LTD), whereas mossy fiber synaptic strengths were not depressed when they received weak inputs out-of-phase with a strong commissural/associational input. Thus, both associative LTP and associative LTD can be induced at commissural/associational synapses, but not at mossy fiber synapses.

Action Potentials↗
PubMed1992

Freeze-etched postsynaptic membranes in the visual cortex reveal different types of synapses including mixed synapses.

The intramembranous structure of the postsynaptic membranes in the rat visual cortex was examined. Simple, complex and mixed synapses were differentiated according to the shape of the postsynaptic particle aggregations. The present data support the existence of all intermediate stages schematically presented in the hypothesis describing a synapse division. The advantage of the freeze-etching technique for the study of the shape of the active zones is emphasized.

Animals↗
PubMed1977

Monoaminergic synapses, including dendro-dendritic synapses in the rat substantia nigra.

Intraventricular administration of 1 or 2 mg of the osmiophilic "false transmitter" 5-hydroxydopamine (5-OHDA) was used to label monoamine storage and release sites in the rat substantia nigra. Vesicles containing unusually dense cores indicative of the presence of the marker were seen forming from the Golgi apparatus in the cell bodies of medium-sized neurons of the substantia nigra, pars compacta, and from smooth endoplasmic reticulum in the dendrites of those neurons and in small unmyelinated axons of unknown origin. In serial sections, both axons and dendrites containing synaptic vesicles marked with 5-OHDA were seen to form synapses "en passage" in pars compacta, and some presynaptic dendrites containing vesicles filled by the marker were also observed to form contacts with dendrites in pars reticulata. The only identified postsynaptic elements engaging in monoaminergic synapses in the substantia nigra were dendrites of medium-sized pars compacta neurons.

Animals↗
PubMed1989

Differential effects of phospholipase inhibitors in long-term potentiation in the rat hippocampal mossy fiber synapses and Schaffer/commissural synapses.

Bath application of the inhibitors of phospholipases, nordihydroguaiaretic acid (NDGA) and p-bromo-phenacyl bromide (BPB), to the rat hippocampal slices suppressed long-term potentiation (LTP) in Schaffer/commissural-CA1 pyramidal synapses. On the other hand, neither of the two inhibitors suppressed LTP in mossy fiber-CA3 pyramidal cell synapses. BPB did not suppress phosphatidylinositol-specific phospholipase C (PI-PLC) activity of the slices. These results suggested that the mechanisms of LTP were quite different in the CA1 and CA3 subfields of rat hippocampus: in CA1, the involvement of an arachidonate metabolism was strongly suggested, whereas in CA3, an arachidonic acid cascade may not be necessary for LTP.

Acetophenones↗
PubMed1990

Anti-GABA antibodies label a subpopulation of chemical synapses which modulate an electrical synapse in crayfish.

Antibodies raised against gamma-aminobutyric acid (GABA) were used to stain sections from the crayfish abdominal nervous system, and the sections were examined under the electron microscope using a protein-A/gold conjugate secondary label. Sections were taken through the third ganglionic root, and through the interganglionic connective at the base of the third root posterior to the ganglia. The third root contains two very large motor axons, a non-GABAergic excitor (Motor Giant; MoG), and a GABAergic inhibitor (Flexor Inhibitor; FI). Only one of the two large axons stained positively for GABA, confirming that the antibody has high specificity for GABAergic neurones. The MoG is driven by powerful electrical synapses from the giant fibres, but also receives inhibitory chemical synaptic input which can gate the excitatory input. There is no physiological evidence for any other form of chemical input. However, at the ultrastructural level, the MoG is postsynaptic to three types of chemical profiles; SE-type containing round agranular vesicles, SI-type containing pleomorphic vesicles, and SM-type containing a mixture of round agranular and dense-cored vesicles. There is a highly differentiated staining pattern of these three synaptic types. Only the SI-type profiles stain positively with the GABA antibody, while the SE- and SM-type do not show significant staining. This suggests that the MoG can under some circumstances receive chemical input other than GABAergic inhibitory input. These other types of input have yet to be physiologically identified.

Animals↗
PubMed1987

Saphenous has weak ineffective synapses in sciatic territory of rat spinal cord: electrical stimulation of the saphenous or application of drugs reveal these somatotopically inappropriate synapses.

In a previous paper, we showed that chronic denervation of the sciatic nerve for more than 21 days in adult rats caused expansion of the saphenous nerve into sciatic territory in the spinal cord (medial L4, L5 and L6). To try to explain this expansion in the present paper, we tested the hypothesis that weak ineffective synapses of saphenous terminals are always present in sciatic territory. For this purpose the sciatic nerve was acutely denervated, the cord mapped with microelectrodes and responses evoked in single cells with natural (mechanical cutaneous) or electrical (pulses to saphenous nerve) stimulation. In the sciatic territory, no natural responses occurred but electrically evoked responses from the saphenous were everywhere. When drugs were applied to potentiate synaptic activity, many of the silent neurons in the sciatic territory in L4, L5 and L6 responded to natural inputs mediated by the saphenous. Picrotoxin was more effective than 4-aminopyridine which was more effective than strychnine in expressing these weak somatotopically inappropriate saphenous inputs. All together, these results support the hypothesis that weak ineffective saphenous inputs exist in sciatic territory of the spinal cord. They can be artificially expressed with electrical volleys or chemical potentiation and may be naturally expressed several weeks after chronic lesions of the sciatic nerve.

4-Aminopyridine↗
PubMed1985

The human posterior tibial somatosensory evoked potential: synapse dependent and synapse independent spinal components.

Evidence has been obtained for the existence of two separate events occurring in the human spinal cord following posterior tibial nerve (PTN) stimulation. These events can be recorded on the surface in unanesthetized individuals. The first is an ascending wave which is conducted up to the cord at constant velocity and has a relatively short refractory period consistent with a compound nerve action potential. This represents the afferent volley traversing the lumbosacral plexus and the ascending dorsal columns. A second event, the N22/P22 complex, is surface negative on the back and surface positive anteriorly; its amplitude is maximal 5-15 cm above the level of the L4 spine and its peak latency remains constant at all levels. This activity has a relatively long refractory period. These characteristics of N22/P22 indicate that it is a localized synaptically dependent event conforming to a transverse dipole with dorsal negativity and a simultaneous anterior positivity. The N22/P22 is probably generated in the dorsal grey at the root entry zone. The N22/P22 is analogous to the stationary N13/P13 recorded over the neck following median nerve stimulation.

Adult↗
PubMed1976

A quantitative comparison of the formation of synapses in the rat superior cervical sympathetic ganglion by its own and by foreign nerve fibres.

The rat superior cervical sympathetic ganglion (SCG) has about 36,000 neurones in a volume of about 1 cu.mm. There are about 8.8 X 10(6) synapses, and 6000-9000 preganglionic axons. Section of the preganglionic chain causes a loss of 93% of the synapses. In the denervated SCG there are 0.6 X 10(6) remaining ('intrinsic') synapses, and a proportion of the synaptic sites are identifiable as vacated synaptic thickenings (3 X 10(6) per SCG, as compared with 0.5 X 10(6) in the normal intact SCG). After deducting the intrinsic synapses, this indicates that each preganglionic axon forms about 1100 (900-1400) synapses. After freezing the preganglionic chain, subsequent axonal regeneration restores synapse numbers to 85% of normal (7.5 X 10(6) synapses per SCG). After anastomotic repair by suture of the cut ends of the preganglionic chain (a necessary control for the foreign nerve anastomoses), the SCG contains only 60% of the normal complement of synapses (5.2 X 10(6) synapses per SCG). The results of this anastomosis are very variable. However, in individual ganglia the numbers of synapses are directly correlated with the numbers of axons which reach the SCG. After deducting the intrinsic synapses it can be calculated that each axon forms about 700 synapses. This is probably an underestimation of the numbers which would be achieved at longer survival times. After anastomosis of the vagal nerve into the denervated SCG there are about 4.4 X 10(6) synapses per SCG. Morphologically the majority have axon terminals with large dense cored vesicles, and it is likely that these belong to the axons of the parasympathetic preganglionic neurones in the dorsal motor nucleus of the vagus. A smaller population of axon terminals are devoid of large dense cored vesicles; their origin is unknown. The dorsal motor nucleus of the vagus has between 1000 and 2000 neurones. After deducting the intrinsic synapses, this indicates that each axon may form up to 1900-3800 synapses. To the extent that other, unidentified vagal fibres also contribute to the synapses found after this anastomosis, this figure is an overestimate. After anastomosis of the hypoglossal nerve into the denervated SCG, there are 1.5 X 10(6) synapses per SCG. A morphologically distinctive type of axon terminal is found, and it is argued that this may belong to a special category of skeletomotor neurones located in the caudoventral part of the hypoglossal nucleus and distinguished by pseudocholinesterase staining. There are about 600 of these neurones, which would indicate that they form about 1500 synapses per axon (after deducting the numbers of intrinsic synapses). The majority of the hypoglossal neurones do not form intraganglionic synapses; this suggests that although the possession of a cholinergic mechanism may be necessary for axons to be able to form ganglionic synapses, it is not in itself sufficient. For each of the types of anastomosis, the numbers of vacated thickenings are inversely proportional to the numbers of synapses...

Acetyltransferases↗
PubMed1991

Perforated and non-perforated synapses in rat neocortex: three-dimensional reconstructions.

Perforated and non-perforated synapses in the molecular layer of rat parietal cortex have been assessed morphologically and quantitatively using three-dimensional reconstructions of the postsynaptic terminal. Perforated synapses were analyzed at nine ages, ranging from 0.5 to 22 months of age, and non-perforated synapses at three ages--0.5, 12, and 22 months. Examination of the reconstructions shows that perforated synapses increase in size and complexity with increasing age. This increasing complexity is reflected in a break-up of the postsynaptic density, which is punctuated by larger, branched perforations. In the most extreme cases the result is the appearance of isolated islands of postsynaptic density separated by, and also surrounded by, a synaptic contact zone. Spinules are especially prominent at around 12 months of age in perforated synapses, and the overall negative curvature of the young junctions is replaced by positively curved junctions from 4 months onwards. The non-perforated synapses are relatively small and show few changes with increasing age. Using the measurement option in the reconstruction program, the following trends emerged. All parameters of perforated synapses increased in size with increasing age, whereas the corresponding parameters of non-perforated synapses remained relatively unchanged over this age range. In addition, the percentage of the synaptic contact zone surface area occupied by the postsynaptic density decreased with increasing age in perforated synapses, but increased in non-perforated synapses. The total postsynaptic density surface area of non-perforated synapses per unit volume of molecular layer was double that of perforated synapses at 0.5 months, but the situation was reversed at 12 months. This parameter was similar in the 2 populations at 22 months. This suggests that perforated synapses contribute more to the total surface area of the postsynaptic density in mid- to late-adulthood than do non-perforated synapses, despite non-perforated synapses outnumbering perforated by 2-3:1 at these ages. These data provide more specific evidence that perforated and non-perforated synapses constitute separate synaptic populations from early in development, and that perforated synapses are responsible for the maintenance of neuronal postsynaptic density surface area from mid-adulthood onwards.

Animals↗
PubMed1976

Dendroaxonic synapses in the substantia gelatinosa glomeruli of the spinal trigeminal nucleus of the cat.

The glomeruli in the substantia gelatinosa layer of the spinal trigeminal nucleus of the cat contain three kinds of dendritic processes. One of these, the type 2 dendrite, contains large synaptic vesicles in its spine heads and in its shafts. The type 2 dendrite receivers axodendritic synapses from primary trigeminal afferent (C) axons and an occasional axodendritic synapse from small axonal (P) endings with small synaptic vesicles. The type 2 dendrites in turn form dendroaxonic synapses on the C endings. The dendroaxonic synapse and the axodendritic synapse of the C ending typically occur in reciprocal pairs. The axodendritic synapse usually lies in the depths of scalloped depressions in the surface of the C ending while the dendroaxonic synapse is found on the rim of the depression. Type 1 spines, i.e., dendritic spines receiving axodendritic synapses from the primary ending and lacking synaptic vesicles, also receive dendrodentritic synapses from type 2 dendrites. The type 2 dendrite with its large, rounded synaptic vesicles is considered to be excitatory at its dendroaxonic and dendrodendritic synapses. The type 2 dendrites course from glomerulus to glomerulus receiving their excitatory input through the axodendritic synapses of C axons. A type 2 dendrite, in response to C axon excitation would activate type 1 spines directly through their dendrodendritic synapses (C leads to 2 leads to 1) and indirectly by increasing transmitter release at the axodendritic synapses of the C axonal endings through their dendroaxonic synapses (2 leads to C leads to 1). The type 2 dendrites could serve two functions. First, they may prolong transmitter release from the axodendritic synapses of C axonal endings beyond the time of arrival of incoming potentials because of the reciprocal pairing of dendroaxonic and axodendritic synapses (C in equilibrium 2). Second, they may extend the spatial range of the excitatory output of active primary afferent axons to type 1 spines of glomeruli whose primary afferent axons may be inactive (C leads to 2 leads to 1).

Animals↗
PubMed1976

Synapse formation in the mouse olfactory bulb. I. Quantitative studies.

A quantitative study of synapse formation in the mouse olfactory bulb has been carried out using serial sections. Volumetric synaptic density as well as absolute number of synapses per olfactory bulb for eight distinct synaptic types have been determined at 15 different ages, from the beginning of synapse formation at embryonic day 14 (E14) to postnatal day 44 (P44). Synapses are first found in appreciable numbers at E15 when both axo-dendritic and a few dendro-dendritic synapses occur in the presumptive glomerular layer. Initial synapse formation correlates closely with the reorientation of mitral cells from a primitive tangenital to a definitive radial direction. Synapse formation by mitral cell dendrites occurs after mitral cell axons have grown into the future olfactory cortical areas, either simultaneous with or before synapse formation by these axons. Virtually all synaptic types detected in adults have been found on the day of birth, consistent with the idea that olfaction is an important sensory modality for newborn mice. Volumeric density of a given synaptic type generally increases 50--100 times during development while the absolute number increases about 1,000 times. Synapses in glomeruli develop more precociously than those in the time of origin and differentiation of the principal postsynaptic elements of these two divisions (mitral cells and internal granule cells). Correlation of the time of synapse formation of various synaptic types with their putative excitary or inhibitory role determined in adult studies suggests that excitatory synapses generally form somewhat earlier, although throughout nearly all of synaptic development, both excitatory and inhibitory synapses are present. Reciprocal dendro-dendritic synapses in the external plexiform layer appear to have a special mode of formation. It is suggested that a granule-to-mitral dendro-dendritic synapse only forms next to an already existing mitral-to-granule synapse on the same gemmule.

Age Factors↗