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At least 19 recordsLinked to original sources

Thin-section and freeze-fracture studies of crayfish stretch receptor synapses including the reciprocal inhibitory synapse.

The crayfish slow-adapting abdominal stretch receptor organ is innervated by three inhibitory and several excitatory axons. A previous study by Tisdale and Nakajima ('76) showed that under certain fixation conditions inhibitory and excitatory synapses can be distinguished on the basis of synaptic vesicle structure. Using this morphological criterion we describe six types of synapses in the receptor: (1) the inhibitory axo-dendritic synapse, (2) the excitatory neuromuscular synapse, (3) the inhibitory neuromuscular synapse, (4) the axo-axonic synapse which suggests presynaptic inhibition of the excitatory synapse, (5) the axo-axonic synapse which suggests presynaptic inhibition on the inhibitory synapse, (6) the reciprocal inhibitory axo-axonic synapse, which is a new type of synapse. The presence of these six types of synapse suggest that inhibitory and excitatory axons interact synaptically in a complicated manner, resulting in a delicate control of receptor function. In freeze fracture we have observed the presynaptic membrane structures of inhibitory and excitatory synapses. The active zone of the inhibitory synapse has ridges with loosely aggregated particles on the tops of the ridges and indentations (vesicle attachment sites) along their sides. The active zone of the excitatory neuromuscular synapse consists of bands of particle aggregates which are situated on slightly elevated membrane regions and surrounded by wide, relatively particle-free, flat membrane areas.

Animals↗

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↗

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↗

Axospinous synapses with segmented postsynaptic densities: a morphologically distinct synaptic subtype contributing to the number of profiles of 'perforated' synapses visualized in random sections.

Axospinous synapses were examined in the molecular layer of the rat dentate gyrus. Serial section analysis of synapses, which exhibited a discontinuity of the postsynaptic density (PSD) in at least one consecutive section, was performed. Reconstruction of each discontinuous PSD was made in a plane perpendicular to that of serial sections. The results obtained confirm earlier observations that profiles of 'perforated' synapses visualized in random sections of osmicated material are produced by sectioning of synapses with perforated and horseshoe-shaped PSDs. Additionally, it has been found that two other synaptic subtypes, namely synapses with notched and segmented PSD, contribute to the number of profiles of 'perforated' synapses. Synaptic contacts with notched PSD are characterized by an indentation of an otherwise continuous PSD, relatively small dimensions and simple shape. They appear to be unrelated to the category of synapses with discontinuous PSD. Synaptic contacts with segmented PSD are distinguished by the presence of 2-5 discrete PSD segments at the interface between a presynaptic axon terminal and a postsynaptic dendritic spine. Some PSD segments exhibit 1-3 perforations, while others are horseshoe-shaped. It is postulated that the segmented PSD may evolve through the stages of perforated and horseshoe-shaped PSD to form a specialized synaptic contact of an unusually high efficacy. Every PSD segment is a component of a separate synaptic complex, each one comparable to that of a small, simple-shaped synapse. A concerted activation of several synaptic complexes belonging to a single synaptic junction may provide a mechanism for an amplification of synaptic transmission.

Aging↗

Molecular organization of a type of peripheral glutamate synapse: the afferent synapses of hair cells in the inner ear.

The synapses between sensory cells in the inner ear and the afferent dendrites of ganglion cells are well suited to investigations of fundamental mechanisms of fast synaptic signalling. The presynaptic elements can be isolated for electrophysiological and functional studies while the synapses can be easily recognized in the electron microscope due to their distinct morphological features. This allows for a broader range of correlative functional and structural analyses than can be applied to synapses in the central nervous system (CNS). As in most fast excitatory synapses in the CNS the transmitter in the afferent hair cell synapses appears to be glutamate or a closely related compound. Recent studies have revealed many of the key molecular players at this type of synapse and how they are spatially and functionally coupled. By use of high resolution immunogold cytochemistry it has been shown that AMPA glutamate receptors are specifically expressed in the postsynaptic specialization of afferent hair cell synapses (except at those established by outer hair cells in the organ of Corti) and that their density varies as a function of the distance from the release sites (demonstrated for the afferent contacts of inner hair cells). The glutamate transporter GLAST is localized in supporting cell membranes and concentrated in those membrane domains that face the synaptic regions. Glutamine synthetase and phosphate-activated glutaminase--which are responsible for the interconversion of glutamate and glutamine--are selectively localized in non-neuronal and neuronal elements, respectively. Taken together with quantitative immunogold data on the cellular compartmentation of glutamate and glutamine the above findings suggest that the sensory epithelia in the inner ear sustain a cycling of glutamate carbon skeletons. In this process, the supporting cells may carry out functions analogous to those of glial cells in the CNS. Functional and morphological analyses of the presynaptic membrane indicate that L-type Ca(2+)-channels and Ca(2+)-activated K(+)-channels are colocalized and clustered at the active zone. Influx through the L-type channels triggers synaptic release and their close spatial association with Ca(2+)-activated K(+)-channels appears to be critical for frequency tuning. The focal expression of different Ca(2+)-channels combined with a high intracellular buffering capacity permits several Ca(2+)-signalling pathways to operate in parallel without undue interference. The molecular organization of the afferent hair cell synapses reflects the functional demand for speed and precision and attests to the ability of the pre- and postsynaptic elements to target and anchor key proteins at specific membrane domains.

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Correlation of a dynamic model for immunological synapse formation with effector functions: two pathways to synapse formation.

During antigen recognition by T cells different receptors and ligands form a pattern in the intercellular junction called the immunological synapse, which might be involved in T-cell activation. Recently, a synapse assembly model has been proposed, which enables the calculation of the propensity for synapse assembly driven by membrane-constrained protein binding interactions. We bring together model predictions of mature synapse assembly with data on the dependence of T-cell responses on T-cell receptor (TCR)-MHC-peptide (pMHC) binding kinetics. Predictions of mature synapse assembly, based on TCR-pMHC binding kinetics, correlate well with observed cytokine responses by T cells bearing the relevant TCR but not with cytotoxic T lymphocyte-mediated killing. We discuss the suggested different role for the synapse in pre- and post-nuclear activation events in T cells. The view of immunological synapse assembly given here emphasizes the importance of both the on and off rates for the TCR-pMHC interaction and in this context recent data on a positive role for analogs of self-peptides in synapse assembly is considered.

Animals↗

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↗

[Immunological synapses and neuronal synapses].

The interface between two cells from the immune system has recently been coined "immunological synapse". The authors review recent findings concerning the structure of the synapse formed between T lymphocytes and antigen-presenting cells. T cells can be part of different synapses, depending on the antigen-presenting cell (B cell hybridoma, proteo-lipid bilayer, macrophage, dendritic cell). The synapse formed with dendritic cells is discussed in more details. A comparison is made with the synapses from the nervous system. Several parallel questions are discussed: how receptors can be clustered, what is the influence of synapse functioning on the structure of the synapse. It is suggested that in both cases two modes of communication exist in parallel: direct cell-cell contacts and soluble mediators, neurotransmitters in one case, putative immunotransmitters in the other.

Antigen-Presenting Cells↗

Rab3 proteins and SNAP-25, essential components of the exocytosis machinery in conventional synapses, are absent from ribbon synapses of the mouse retina.

GTP-binding rab proteins, present in synaptic vesicles and endocrine secretory granules, have been shown to be involved in the control of regulated exocytosis. We found rab3 proteins in immunoblots of diverse areas of the mouse central nervous system (spinal cord, olfactory bulb, hippocampus, cerebellum and neocortex). Immunohistochemical observations at light- and electron-microscopical levels in the hippocampus and other areas revealed rab3 proteins in virtually all synaptic fields and terminals of the areas investigated. In the retina, rab3A immunoreactivity was confined to the inner and outer plexiform layers. Ultrastructural examination revealed that rab3A was present in conventional terminals in the inner plexiform layer and in horizontal cell processes of the outer plexiform layer. In contrast ribbon synapses, which play a key role in transferring information from the photoreceptor cells to the central nervous system, were immunonegative. We also tested whether other proteins of the rab3 family are present in ribbon synapses. However, using an antibody recognizing rab3B and rab3C in addition to rab3A, we found no immunoreactivity in these synapses. Interestingly, we observed also no immunoreactivity for synaptosomal-associated protein 25 (SNAP-25) in ribbon synapses, but conventional synapses and horizontal cell processes were heavily stained. Our data show that the known rab3 and SNAP-25 isoforms, which are components of the secretory apparatus of conventional synapses, are absent from ribbon synapses of the retina. Our observations suggest different mechanisms of transmitter exocytosis in conventional and ribbon terminals.

Animals↗

Protein synthesis at synapse versus cell body: enhanced but transient expression of long-term facilitation at isolated synapses.

Protein synthesis at synaptic terminals contributes to LTP in hippocampus and to the formation of new synaptic connections by sensory neurons (SNs) of Aplysia. Here we report that after removal of the SN cell body, isolated SN synapses of Aplysia in culture express protein-synthesis dependent long-term facilitation (LTF) produced by 5-HT that decays rapidly. Changes in expression of a SN-specific neuropeptide sensorin in isolated SN varicosities parallel the changes in synaptic efficacy. At 24 h after 5-HT the magnitude of LTF produced at isolated SN synapses was significantly greater than that produced when SN cell bodies were present. LTF was maintained at 48 h at connections with SN cell bodies, but not at isolated SN synapses. The increase in synaptic efficacy at isolated SN synapses at 24 h was blocked by the protein synthesis inhibitor anisomycin. LTF was accompanied by changes in expression of sensorin. The increase in sensorin level at isolated SN varicosities with 5-HT was blocked by anisomycin or was reversed 48 h after 5-HT treatment alone. The results suggest that, as is the case for initial synapse formation between SNs and L7, changes in protein synthesis at synaptic terminals may contribute directly to LTF of stable synapses. Changes in expression within the cell body provide additional contributions for long-term maintenance of the new level of synaptic efficacy that was initiated directly by local changes in protein synthesis at or near synaptic terminals.

Animals↗

Plasticity of the parallel fiber-Purkinje cell synapse by spine takeover and new synapse formation in the adult rat.

Alteration in synaptic connectivity between Purkinje cell spines and parallel fibers of the cerebellum were studied following partial deafferentation of Purkinje cells in the the adult rat. Transection of parallel fibers by two lesions placed at a 1 mm interval on the folial crest were used to produce degeneration of these afferents. Ultrastructural analysis of synapses on Purkinje cell spines revealed degeneration with vacating of postsynaptic sites within 6 h. Reactive synaptogenesis as takeover of Purkinje cell spines by formation of new synapses from remaining parallel fibers occurred even before degenerating parallel fibers had vacated postsynaptic sites. This was accompanied by a marked increase in the number of dual innervations by reactive parallel fibers within one day. Some vacated postsynaptic sites were lost as indicated by a reduction in the number of synapses and others may have been taken over by newly formed synapses on spines. In addition, new synapses formed between the shafts of Purkinje cell branchlets and parallel fibers. Sprouting of parallel fibers occurred as small extensions without tubules while Purkinje cell spines reacted by forming elongated and multiple heads which contacted different parallel fibers. After 5 days degenerating boutons were rarely found. Enlarged spine heads were each capped by a proportionally enlarged parallel fiber bouton and joined by an elongated synaptic junction to parallel fibers. Some parallel fiber boutons were greatly enlarged and capped numerous profiles of spines. This study shows that formation of new pre- and postsynaptic sites takes precedence over reoccupation of original contacts and that multiple synapses on individual spines are being eliminated to give rise to single contacts with boutons. This elimination resulted in enlargement of synaptic contact areas between Purkinje cell spines and parallel fibers by taking over postsynaptic sites from some vacated and eliminated boutons.

Animals↗

Differential rearing effects on rat visual cortex synapses. I. Synaptic and neuronal density and synapses per neuron.

The bulk of the evidence indicating that different experiences can lead to differences in synapse numbers involves inference from measures of postsynaptic surface (spines and dendrites) in Golgi impregnated tissue. The capriciousness of Golgi impregnation and the absence of direct evidence regarding changes in afferents mandate confirmation of synapse changes by electron microscopy. We calculated the ratio of synapses per neuron in layers I-IV of occipital cortex of rats reared in complex (EC), social (SC), or isolated (IC) environments. Synaptic density estimates were derived from electron micrographs of osmium-uranyl-lead stained tissue and neuronal density estimates were derived from toluidine blue stained semithin sections using stereological methods which correct for group differences in the sizes of synapses and neuronal nuclei. The ratio of these densities, synapses per neuron, was highest in complex environment rats, intermediate in socially reared rats and lowest in isolates, in accordance with predictions from prior Golgi studies. The bulk of the differences were attributable to neuronal density, which was highest in IC rats and lowest in ECs. Synaptic density did not differ statistically across groups. These results indicate, at least within this area and paradigm, that differences in dendritic measures in Golgi impregnated tissue reflect differences in the number of synapses per neuron.

Animals↗

Differential localization of delta glutamate receptors in the rat cerebellum: coexpression with AMPA receptors in parallel fiber-spine synapses and absence from climbing fiber-spine synapses.

The delta 2 glutamate receptors are prominently expressed in Purkinje cells and are thought to play a key role in the induction of cerebellar long-term depression. The synaptic and subsynaptic localization of delta receptors in rat cerebellar cortex was investigated with sensitive and high-resolution immunogold procedures. After postembedding incubation with an antibody raised to a C-terminal peptide of delta 2, high gold particle densities occurred in all parallel fiber synapses with Purkinje cell dendritic spines, whereas other synapses were consistently devoid of labeling. Among the types of immunonegative synapse were climbing fiber synapses with spines and parallel fiber synapses with dendritic stems of interneurons. At the parallel fiber-spine synapse, gold particles signaling delta receptors were restricted to the postsynaptic specialization. By the use of double labeling with two different gold particle sizes, it was shown that delta and AMPA GluR2/3 receptors were colocalized along the entire extent of the postsynaptic specialization without forming separate domains. The distribution of gold particles representing delta receptors was consistent with a cytoplasmic localization of the C terminus and an absence of a significant presynaptic pool of receptor molecules. The present data suggest that the delta 2 receptors are targeted selectively to a subset of Purkinje cell spines and that they are coexpressed with ionotropic receptors in the postsynaptic specialization. This arrangement could allow for a direct interaction between the two classes of receptor.

Animals↗

Development of axosomatic synapses of the Xenopus spinal cord with special reference to subsurface cisterns and C-type synapses.

The relationships of highly flattened subsurface cisterns (SCCs) were investigated electron microscopically in the spinal cord at various developmental stages of tadpoles and adult toads, Xenopus laevis. In medial ventral motor cells (MVCs) of the adult, more than 90% of 156 SSCs examined were situated postsynaptically. Similarly, more than 90% of 540 SSCs in lateral motor column cells (LMCs) were postsynaptic. By contrast, in early developmental stages, the SSCs were initially formed by regional flattening of cisterns of rough-surfaced endoplasmic reticulum just beneath the cell surfaces opposite to glial processes. Then, the glial processes were displaced by nerve endings with an elongated bouton, and thus the C-type synapses were formed. The ratio of postsynaptic SSCs to the total SSCs reached the adult level at around Stage 60. This finding suggests that the SSCs in the MVCs and LMCs draw a certain type of nerve ending to form C-type synapses. Such a mechanism is totally lacking in the dorsal and lateral small nerve cells, since the SSCs in these cells were always situated under the surface opposite to glial processes throughout the developmental stages and in the adult. In mature C-type synapses, an aggregate of synaptic vesicles and a structural specialization of presynaptic membrane occurred only at the region where the postsynaptic membrane was associated with the SSC. The postsynaptic membrane itself of the C-type synapse showed no marked structural specialization at any stage of development or in the adult. The postsynaptic SSC In the mature C-type synapse seems to be involved in some way in the reception of synaptic transmission.

Animals↗

Synaptic plasticity at thalamocortical synapses in developing rat somatosensory cortex: LTP, LTD, and silent synapses.

Thalamocortical synaptic transmission in the rat's primary somatosensory (S1) cortex is modified by sensory experience during a critical period early in life. Despite the importance of such plasticity for the maturation of thalamocortical circuits, the synaptic basis of this plasticity is unknown. Here, we review evidence suggesting that long-term potentiation and depression (LTP and LTD) of thalamocortical synaptic transmission may be involved in this plasticity. In an in vitro slice preparation, thalamocortical synaptic responses exhibit N-methyl-D-aspartate (NMDA) receptor-dependent LTP and LTD during a developmental period similar to the critical period in vivo. The inability to induce LTP and LTD after the critical period may result in part from a developmental reduction in the duration of NMDA receptor currents. In addition, during the critical period many thalamocortical synapses exhibit NMDA receptor currents but no detectable AMPA receptor currents, and thus may be functionally silent at resting membrane potentials. LTP converts silent synapses to functional ones by causing the rapid appearance of AMPA currents. These observations suggest that thalamocortical synapses may be formed as silent synapses which are subsequently made functional by LTP. LTP and LTD may then regulate the efficacy of these functional synapses and thereby contribute to experience-dependent changes in S1 thalamocortical circuits.

Animals↗

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↗

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↗