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PubMed1999

The Drosophila NSF protein, dNSF1, plays a similar role at neuromuscular and some central synapses.

The N-ethylmaleimide sensitive fusion protein (NSF) was originally identified as a cytosolic factor required for constitutive vesicular transport and later implicated in synaptic vesicle trafficking as well. Our previous work at neuromuscular synapses in the temperature-sensitive NSF mutant, comatose (comt), has shown that the comt gene product, dNSF1, functions after synaptic vesicle docking in the priming of vesicles for fast calcium-triggered fusion. Here we investigate whether dNSF1 performs a similar function at central synapses associated with the well-characterized giant fiber neural pathway. These include a synapse within the giant fiber pathway, made by the peripherally synapsing interneuron (PSI), as well as synapses providing input to the giant fiber pathway. The latency (delay) between stimulation and a resulting muscle action potential was used to assess the function of each class of synapses. Repetitive stimulation of the giant fiber pathway in comt produced wild-type responses at both 20 and 36 degrees C, exhibiting a characteristic and constant latency between stimulation and the muscle response. In contrast, stimulation of presynaptic inputs to the giant fiber (referred to as the "long latency pathway") revealed a striking difference between wild type and comt at 36 degrees C. Repetitive stimulation of the long latency pathway led to a progressive, activity-dependent increase in the response latency in comt, but not in wild type. Thus the giant fiber pathway, including the PSI synapse, appears to function normally in comt, whereas the presynaptic inputs to the giant fiber pathway are disrupted. Several aspects of the progressive latency increase observed in the long latency pathway can be understood in the context of the activity-dependent reduction in neurotransmitter release we observed previously at neuromuscular synapses. These results suggest that repetitive stimulation causes a progressive reduction in neurotransmitter release by presynaptic inputs to the giant fiber neuron, resulting in an increased latency preceding a giant fiber action potential. Thus synapses presynaptic to the giant fiber appear to utilize dNSF1 in a manner similar to the neuromuscular synapse, whereas the PSI chemical synapse may differ with respect to the expression or activity of dNSF1.

Animals↗
PubMed1993

Expression of synaptotagmin in Drosophila reveals transport and localization of synaptic vesicles to the synapse.

Synaptotagmin is a synaptic vesicle-specific integral membrane protein that has been suggested to play a key role in synaptic vesicle docking and fusion. By monitoring Synaptotagmin's cellular and subcellular distribution during development, it is possible to study synaptic vesicle localization and transport, and synapse formation. We have initiated the study of Synaptotagmin's expression during Drosophila neurogenesis in order to follow synaptic vesicle movement prior to and during synapse formation, as well as to localize synaptic sites in Drosophila. In situ hybridizations to whole-mount embryos show that synaptotagmin (syt) message is present in the cell bodies of all peripheral nervous system neurons and many, if not all, central nervous system neurons during neurite outgrowth and synapse formation, and in mature neurons. Immunocytochemical staining with antisera specific to Synaptotagmin indicates that the protein is present at all stages of the Drosophila life cycle following germ band retraction. In embryos, Synaptotagmin is only transiently localized to the cell body of neurons and is transported rapidly along axons during axonogenesis. After synapse formation, Synaptotagmin accumulates in a punctate pattern at all identifiable synaptic contact sites, suggesting a general role for Synaptotagmin in synapse function. In embryos and larvae, the most intense staining is found along two broad longitudinal tracts on the dorsal side of the ventral nerve cord and the brain, and at neuromuscular junctions in the periphery. In the adult head, Synaptotagmin localizes the discrete regions of the neurophil where synapses are predicted to occur. These data indicate that synaptic vesicles are present in axons before synapse formation, and become restricted to synaptic contact sites after synapses are formed. Since a similar expression pattern of Synaptotagmin has been reported in mammals, we propose that the function of Synaptotagmin and the mechanisms governing localization of the synaptic vesicle before and after synapse formation are conserved in invertebrate and vertebrate species. The ability to mark synapses in Drosophila should facilitate the study of synapse formation and function, providing a new tool to dissect the molecular mechanisms underlying these processes.

Animals↗
PubMed2001

Three-dimensional comparison of ultrastructural characteristics at depressing and facilitating synapses onto cerebellar Purkinje cells.

Cerebellar Purkinje cells receive two distinctive types of excitatory inputs. Climbing fiber (CF) synapses have a high probability of release and show paired-pulse depression (PPD), whereas parallel fiber (PF) synapses facilitate and have a low probability of release. We examined both types of synapses using serial electron microscopic reconstructions in 15-d-old rats to look for anatomical correlates of these differences. PF and CF synapses were distinguishable by their overall ultrastructural organization. There were differences between PF and CF synapses in how many release sites were within 1 microm of a mitochondrion (67 vs 84%) and in the degree of astrocytic ensheathment (67 vs 94%). However, the postsynaptic density sizes for both types of synapses were similar (0.13-0.14 microm(2)). For both types of synapses, we counted the number of docked vesicles per release site to test whether this number determines the probability of release and synaptic plasticity. PF and CF synapses had the same number of anatomically docked vesicles (7-8). The number of docked vesicles at the CF does not support a simple model of PPD in which release of a single vesicle during the first pulse depletes the anatomically docked vesicle pool at a synapse. Alternatively, only a fraction of anatomically docked vesicles may be release ready, or PPD could result from multivesicular release at each site. Similarities in the number of docked vesicles for PF and CF synapses indicate that differences in probability of release are unrelated to the number of anatomically docked vesicles at these synapses.

Animals↗
PubMed1983

Quantitative features of synapse formation in the fly's visual system. I. The presynaptic photoreceptor terminal.

Photoreceptors of the adult fly's compound eye each form a population of stereotyped output synapses distributed over the surface of their terminal. The formation of this class of afferent synapses during development has been followed from serial electron microscopy of the same eye region in four pupal and several adult stages, all of female Musca domestica. These synapses, or tetrads, have an invariant postsynaptic composition of four members and so may provide a model for multiple-contact synapses in general. In the adult fly the four postsynaptic elements of each synapse are contributed by two interneurons, L1 and L2, and, usually, two alpha processes of an amacrine cell. These postsynaptic elements assemble at individual developing synapses by selective sequential addition. Assembly starts with L1 or L2, subsequent elements of the final tetrad adding in all conceivable permutations, at least as fast as one per 7 hr. They rarely (only once) incorporate incorrect or supernumerary elements, however. The synaptic population as a whole was also sampled during development to analyze the possible factors determining the normal precision of the size of the adult population. The number of synapses per terminal increases gradually until 74% pupal development. Thereafter it decreases so that the final number of synapses in each receptor's population is the consequence of a net loss. Synapses enlarge with age, chiefly by incorporating new elements, but the loss of synaptic sites is only partially offset by the increase in size of those that remain. Throughout all stages examined in pupal and adult life, total synaptic area is linearly proportional to the surface area of the axon terminal. Thus, from the 74% pupal development stage onward, a population of many small synapses closely spaced, on average, over the terminal's surface transforms into one characteristic of the adult with progressively fewer, larger, more widely spaced synapses.

Animals↗
PubMed2001

Localization of the presynaptic cytomatrix protein Piccolo at ribbon and conventional synapses in the rat retina: comparison with Bassoon.

In recent years significant progress has been made in the elucidation of the molecular assembly of the postsynaptic density at synapses, whereas little is known as yet about the components of the presynaptic active zone. Piccolo and Bassoon, two structurally related presynaptic cytomatrix proteins, are highly concentrated at the active zones of both excitatory and inhibitory synapses in rat brain. In this study we used immunocytochemistry to examine the cellular and ultrastructural localization of Piccolo at synapses in the rat retina and compared it with that of Bassoon. Both proteins showed strong punctate immunofluorescence in the outer and the inner plexiform layers of the retina. They were found presynaptically at glutamatergic ribbon synapses and at conventional GABAergic and glycinergic synapses. Although the two proteins were coexpressed at all photoreceptor ribbon synapses and at some conventional amacrine cell synapses, at bipolar cell ribbon synapses only Piccolo was present. Our data demonstrate similarities but also differences in the molecular composition of the presynaptic apparatuses of the synapses in the retina, differences that may account for the functional differences observed between the ribbon and the conventional amacrine cell synapses and between the photoreceptor and the bipolar cell ribbon synapses in the retina.

Animals↗
PubMed2005

GRIP1 in GABAergic synapses.

The glutamate receptor-interacting protein GRIP1 is present in glutamatergic synapses and interacts with the GluR2/3/4c subunits of the AMPA receptors. This interaction plays important roles in trafficking, synaptic targeting, and recycling of AMPA receptors as well as in the plasticity of glutamatergic synapses. Although GRIP1 has been shown to be present at GABAergic synapses in cultured neurons, the use of EM (electron microscopy) immunocytochemistry in the intact brain has failed to convincingly reveal the presence of GRIP1 in GABAergic synapses. Therefore, most studies on GRIP1 have focused on glutamatergic synapses. By using mild tissue fixation and embedding in EM, we show that in the intact brain the 7-PDZ domain GRIP1a/b is present not only in glutamatergic synapses but also in GABAergic synapses. In GABAergic synapses GRIP1a/b localizes both at the presynaptic terminals and postsynaptically, being frequently localized on the synaptic membranes or the synaptic junctional complex. Considerably higher density of GRIP1a/b is found in the presynaptic GABAergic terminals than in the glutamatergic terminals, while the density of GRIP1a/b in the postsynaptic complex is similar in both types of synapses. The results also show that the 7-PDZ and the shorter 4-PDZ domain splice forms of GRIP1 (GRIP1c 4-7) frequently colocalize with each other in individual GABAergic and glutamatergic synapses. The results suggest that GRIP1 splice forms might play important roles in brain GABAergic synapses.

Animals↗
PubMed1994

Distribution of synaptic markers in the retina: implications for synaptic vesicle traffic in ribbon synapses.

Synapses in the retina are present in two layers that can easily be distinguished morphologically: the thin outer plexiform layer (OPL) containing the photoreceptor ribbon synapses, and the more complex inner plexiform layer (IPL) containing mostly conventional synapses. In the current study we have used the exquisite spatial separation between ribbon and conventional synapses in the retina to investigate by immunocytochemistry the protein components of these two types of synapses. Our results show that all of the synaptic vesicle proteins tested are present in the ribbon synapses of photoreceptors except for the synapsins which were previously described to be absent from ribbon synapses. Thus, synaptic vesicles of ribbon and conventional synapses are likely to be very similar molecularly in spite of their different modes of trafficking. Furthermore, proteins with a likely function in synaptic vesicle docking and fusion (SNAP-25, munc-18) and endocytosis (dynamin) were also highly enriched in ribbon synapses, indicating that the basic machineries for synaptic membrane traffic are similar in ribbon and conventional synapses. Interestingly, photoreceptor cells contained only low concentrations of syntaxin I (which functions in the synaptic vesicle fusion complex) and GDI (which regulates the membrane association of rab-proteins as a function of GTP/GDP binding). These results raise the possibility that photoreceptors express other isoforms of these proteins, or that the functions of these proteins are not required for the tonical release mode of their synapses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

Non-NMDA glutamate receptor occupancy and open probability at a rat cerebellar synapse with single and multiple release sites.

1. Excitatory postsynaptic currents (EPSCs) were recorded under whole-cell voltage clamp from granule cells in slices of rat cerebellum. EPSCs from individual mossy fibre inputs were identified by their all-or-none appearance in response to a graded stimulus. Excitatory synaptic transmission was investigated at room temperature (approximately 24 degrees C) and at near-physiological temperature (approximately 34 degrees C) by analysing current fluctuations in the peak and decay of the non-N-methyl-D-aspartate (non-NMDA) component of EPSCs. 2. In a subset of synapses the mean EPSC amplitude remained unchanged as the probability of transmitter release was substantially lowered by raising the extracellular [Mg2+] and lowering [Ca2+]. These synapses were considered to have only one functional release site. Single-site synapses had small EPSCs (139 +/- 16 pS, n = 5, at 24 degrees C) with a large coefficient of variation (c.v. = 0.23 +/- 0.02, n = 5) and an amplitude distribution that was well fitted by a Gaussian distribution in four out of five cases. The EPSC latency had a unimodal distribution and its standard deviation had a temperature dependence with a temperature coefficient (Q10; range, 24-35 degrees C) of 2.4 +/- 0.4 (n = 4). 3. Peak-scaled non-stationary fluctuation analysis of single-site EPSCs indicated that the mean conductance of the underlying non-NMDA channels was 12 +/- 2 pS (n = 4) at 35 degrees C. Upper and lower limits for mean channel open probability (Po), calculated from fluctuations in the EPSC peak amplitude, were 0.51 and 0.38, respectively. These estimates, together with the open probability of the channel when bound by transmitter, suggest that only about 50% of the non-NMDA channels were occupied following the release of a quantum of transmitter. 4. At some multi-site synapses EPSCs had a low c.v. (0.4 +/- 0.01, n = 5) at 34 degrees C and non-stationary fluctuation analysis gave a parabolic variance-mean current relationship. This suggests that practically all of the non-NMDA receptors were occupied by glutamate at the peak of EPSC. The channel open probability (Po = 0.84 +/- 0.03, n = 5) at these 'saturated' multi-site synapses will therefore equal the open probability of the channel when bound by transmitter (Po,max). 5. Non-stationary fluctuation analysis of EPSCs from 'saturating' multi-site synapses indicated that 170 +/- 40 postsynaptic non-NMDA channels were exposed to transmitter at the peak of the EPSC. The mean conductance of the synaptic channels was 10 +/- 2 pS (n = 5) at 34 degrees C. 6. At synapses with multiple release sites the EPSC decay time became faster when release probability was lowered (by reducing the external [Ca2+]/[Mg2+] ratio), indicating that the transmitter concentration profile depended on release probability. No such speeding of the EPSC decay was observed at single-site synapses. 7. Our results suggest that release of a packet of transmitter from a single release site does not saturate postsynaptic non-NMDA receptors at cerebellar mossy fibre-granule cell synapses. However, at multi-site synapses transmitter released from neighbouring sites can overlap, changing the transmitter concentration profile in the synaptic cleft. We conclude that the level of postsynaptic receptor occupancy can depend on the probability of transmitter release at individual multi-site synapses.

Animals↗
PubMed1996

Estradiol increases the frequency of multiple synapse boutons in the hippocampal CA1 region of the adult female rat.

The effect of estradiol to increase the density of dendritic spines and axospinous synapses on hippocampal CA1 pyramidal cells in the adult female rat has been well-documented. However, presynaptic involvement in this process of synapse elimination and formation in the adult is unknown. To address this issue, we have reconstructed 410 complete presynaptic boutons through coded serial electron micrographs of CA1 stratum radiatum to determine the: (1) frequency of multiple (MSB) vs. single (SSB) synapse boutons; (2) number of synaptic contacts per MSB; (3) bouton volume and surface area; and (4) types of spines in synaptic contact with MSBs and SSBs in ovariectomized, estradiol-treated animals (OVX + E) versus ovariectomized oil-treated controls (OVX + O). Quantitative analysis of this tissue revealed that, in OVX + E animals, 45.0% of presynaptic boutons form multiple synaptic contacts with dendritic spines compared to 27.3% in controls (P < 0.01); the average number of synapses per dendritic spines compared to 27.3% in controls (P < 0.01); the average number of synapses per MSB was 2.7 in OVX + E animals compared to 2.3 in controls (P < 0.05). This represents a 25.5% increase in the number of synapses formed by a given number of presynaptic boutons in estradiol-treated animals (P < 0.01) which largely accounts for the previously observed estradiol-induced increase in axospinous synapse density. There was no treatment effect on bouton size; however, because MSBs are larger than SSBs, the increased frequency of MSBs in estradiol-treated tissue results in a trend toward an estradiol-induced increase in average bouton size. Additionally, MSBS were found to be more irregular in shape, i.e., significantly less spherical, than SSBs. Our results indicate that estradiol-induced dendritic spines form synapses primarily with preexisting boutons in stratum radiatum and that these boutons enlarge and change shape as they accommodate new synapses. Such findings suggest a relatively active role for dendrites in the process of adult synapse formation.

Animals↗
PubMed2000

Synapse formation during neuron differentiation: an in situ study of the myenteric plexus during murine embryonic life.

Ultrastructural steps characterizing synapse formation in vivo and appearance in neuroblasts of properties suggestive of synaptic function acquisition have scarcely been studied. Synapse formation and proteosynthetic apparatus organization were thus studied under transmission electron microscope in mouse myenteric neurons from embryonic day 12.5 (E12.5) until birth. Expression of Ret and p75(NTR), markers of neural crest cells, as well as that of neuron-specific enolase (NSE), synaptophysin (SY), and synaptosomal-associated protein (SNAP), markers of synaptic function acquisition, were immunohistochemically evaluated. At E12.5 many cells were Ret- and p75(NTR)-immunoreactive (IR), whereas a few were NSE-IR and had neuronal ultrastructural characteristics. Two types of contacts between poorly or nondifferentiated cells and axons of presumed extrinsic (synapse-like contacts) or local (immature synapses) origin were identified, along with SY-IR elements. By E16. 5, many cells had developed a proteosynthetic apparatus, synapse-like contacts were no longer present, and immature synapses were gradually differentiating. Concurrently, there was an increase in NSE-IR cells, some of which were also SNAP-IR, and in SY-IR varicosities. At E18.5, ultrastructurally mature neurons and synapses had increased in number as had NSE-IR and SNAP-IR cells and SY-IR varicosities. These data indicate that 1) one type of contact (synapse-like) is present at E12.5 between very immature cells and presumed vagal fibers, with a possible transient role for the onset of the differentiative process of these cells; and 2) another type of contact (typical synapses) lasts until E18.5, with a similar but long-lasting role that progressively shifts to the classical function (neurotransmission) as the synapse matures and the embryo reaches the day of birth.

Animals↗
PubMed1990

Synapse loss in frontal cortex biopsies in Alzheimer's disease: correlation with cognitive severity.

Ultrastructural studies of biopsied cortical tissue from the right frontal lobe of 8 patients with mild to moderate Alzheimer's disease (AD) revealed that the number of synapses in lamina III of Brodmann's area 9 was significantly decreased when compared with the number in age-matched control brains (n = 9; postmortem time, less than 13 hours). Further decline in synaptic number was seen in age-matched autopsied AD specimens. In the AD brains there was significant enlargement of the mean apposition length, which correlated with degree of synapse loss; as synapse density declined, synapse size increased. The enlargement of synapses, coupled with the decrease in synaptic number, allowed the total synaptic contact area per unit volume to remain stable in the patients who underwent biopsy. In autopsied subjects who had AD, there was no further enlargement of mean synaptic contact area. There was a significant correlation between synapse counts and scores on the Mini-Mental State examination in the patients who underwent biopsy. Lower mental status scores were associated with greater loss of synapses. Choline acetyltransferase activity was significantly decreased in the biopsied group and declined further in the autopsied specimens of AD. There was no relationship between choline acetyltransferase activity and scores on the Mini-Mental State examination or synapse number. There is evidence of neural plasticity in the AD neuropil; synaptic contact size increased in patients who had biopsy and possibly compensated for the numerical loss of synapses. But by end stage of the disease, the ability of the cortex to compensate was exceeded and both synapse number and synaptic contact area declined.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed2003

Organization of postsynaptic density proteins and glutamate receptors in axodendritic and dendrodendritic synapses of the rat olfactory bulb.

Glutamate neurotransmission in the olfactory bulb involves both axodendritic synapses and dendrodendritic reciprocal synapses and possibly also extrasynaptic receptors. By using a sensitive immunogold procedure, we have investigated the organization of two synaptic scaffolding molecules, PSD-95 and PSD-93, as well as N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) receptors, at these heterogeneous glutamate signaling sites. Immunolabeling for PSD-95 and PSD-93 was present in all major types of putative glutamatergic synapse, suggesting that these proteins are essential components of the synaptic signaling apparatus. The linear density and the subsynaptic distribution of PSD-95/PSD-93 gold particles did not differ significantly between axodendritic and dendrodendritic synapses. Antibodies recognizing NMDA and AMPA receptor subunits also labeled asymmetric synapses throughout the olfactory bulb. Immunolabeling for the AMPA receptor subunits GluR2/3 was similar in all types of synapse. In contrast, immunogold signals for the NR1 subunit of NMDA receptors varied significantly among different synapse populations, with olfactory nerve synapses in the glomerular layer showing the lowest labeling intensity. Although the lateral dendrites of mitral and tufted cells have been reported to respond to glutamate, they did not display significant plasma membrane labeling for the NR1 subunit or for PSD-95, suggesting that the physiological effects of glutamate at these sites are mediated by NMDA autoreceptors that are not clustered and occur only at a low density on the dendritic surface. Our quantitative analysis of olfactory bulb synapses indicates that the density of NMDA receptors is not determined by the complement of PSD-95/PSD-93. The latter molecules appear to be expressed in an all-or-none fashion and may form a standard lattice common to different types of glutamatergic synapse.

Animals↗
PubMed2004

Differences in the expression of AMPA and NMDA receptors between axospinous perforated and nonperforated synapses are related to the configuration and size of postsynaptic densities.

Axospinous synapses are traditionally divided according to postsynaptic density (PSD) configuration into a perforated subtype characterized by a complex-shaped PSD and nonperforated subtype exhibiting a simple-shaped, disc-like PSD. It has been hypothesized that perforated synapses are especially important for synaptic plasticity because they have a higher efficacy of impulse transmission. The aim of the present study was to test this hypothesis. The number of postsynaptic AMPA receptors (AMPARs) is widely regarded as the major determinant of synaptic efficacy. Therefore, the expression of AMPARs was evaluated in the two synaptic subtypes and compared with that of NMDA receptors (NMDARs). Postembedding immunogold electron microscopy was used to quantify the immunoreactivity following single labeling of AMPARs or NMDARs in serial sections through the CA1 stratum radiatum of adult rats. The results showed that all perforated synapses examined were immunopositive for AMPARs. In contrast, only a proportion of nonperforated synapses (64% on average) contained immunogold particles for AMPARs. The number of immunogold particles for AMPARs was markedly and significantly higher in perforated synapses than in immunopositive nonperforated synapses. Although all synapses of both subtypes were NMDAR immunopositive perforated synapses contained significantly more immunogold particles for NMDARs than nonperforated ones. Multivariate analysis of variance revealed that the mode of AMPAR and NMDAR expression is related to the complexity of PSD configuration, not only to PSD size. These findings support the notion that perforated synapses may evoke larger postsynaptic responses relative to nonperforated synapses and, hence, contribute to an enhancement of synaptic transmission associated with some forms of synaptic plasticity.

Animals↗
PubMed2006

Development of gamma-aminobutyric acidergic synapses in cultured hippocampal neurons.

The formation and maturation of gamma-aminobutyric acid (GABA)-ergic synapses was studied in cultured hippocampal pyramidal neurons by both performing immunocytochemistry for GABAergic markers and recording miniature inhibitory postsynaptic currents (mIPSCs). Nascent GABAergic synapses appeared between 3 and 8 days in vitro (DIV), with GABAA receptor subunit clusters appearing first, followed by GAD-65 puncta, then functional synapses. The number of GABAergic synapses increased from 7 to 14 DIV, with a corresponding increase in frequency of mIPSCs. Moreover, these new GABAergic synapses formed on neuronal processes farther from the soma, contributing to decreased mIPSC amplitude and slowed mIPSC 19-90% rise time. The mIPSC decay quickened from 7 to 14 DIV, with a parallel change in the distribution of the alpha5 subunit from diffuse expression at 7 DIV to clustered expression at 14 DIV. These alpha5 clusters were mostly extrasynaptic. The alpha1 subunit was expressed as clusters in none of the neurons at 7 DIV, in 20% at 14 DIV, and in 80% at 21 DIV. Most of these alpha1 clusters were expressed at GABAergic synapses. In addition, puncta of GABA transporter 1 (GAT-1) were localized to GABAergic synapses at 14 DIV but were not expressed at 7 DIV. These studies demonstrate that mIPSCs appear after pre- and postsynaptic elements are in place. Furthermore, the process of maturation of GABAergic synapses involves increased synapse formation at distal processes, expression of new GABAA receptor subunits, and GAT-1 expression at synapses; these changes are reflected in altered frequency, kinetics, and drug sensitivity of mIPSCs.

Animals↗
PubMed1976

Synapse formation in the mouse olfactory bulb. II. Morphogenesis.

Serial thin sections of the mouse olfactory bulb from the fourteenth day of gestation (E14) to postnatal to 44 (P44) have been examined in order to study morphogenesis of individual synaptic junctions. At the initiation of synapse formation structures are found that resemble postsynaptic densities but are facing extracellular space or unmodified processes. Transition forms between these isolated postsynaptic densities and undoubted synapses have been found. These observations as well as quantitative studies support the hypothesis that isolated postsynaptic densities can form independently and be converted to synapses when a presynaptic specialization develops opposite them. Detailed studies of olfactory axodendritic synaptogenesis throughout the entire developmental period suggests strongly that these asymmetrical synapses pass through an immature symmetrical phase: (1) symmetrical olfactory axodendritic synapses are found in significantly higher concentration on axonal and dendritic growth cones than on more common processes; (2) the number of symmetrical synapses is correlated with the rate of formation of new synapses determined previously. The time for a recognizable symmetrical synapse to be transformed into a recognizable asymmetrical one has been calculated to be 9--10 hours. A scheme of synapse formation in the CNS has been proposed in which a post-synaptic structure forms independently followed by aggregation of pre-existing presynaptic components into a presynaptic specialization. Different morphogenetic sequences of synapse formation from region to region are attributed simply to different relative rates in the development of the postsynaptic density and the presynaptic specialization.

Age Factors↗
PubMed1982

Regulation in the number of fly photoreceptor synapses: the effects of alterations in the number of presynaptic cells.

At the equator of the fly's eye, between dorsal and ventral eye halves, a systematic, natural addition of photoreceptor terminal input occurs at each of the fixed populations of uniquely identifiable postsynaptic interneurons in each cartridge of the first optic neuropile, or lamina. The equatorial cartridges are identical in composition except in having seven and eight receptor terminals (7R and 8R, respectively), compared with six elsewhere (6R cartridges). The effects of this augmented presynaptic input upon the frequency of the chief afferent class of photoreceptor tetrad synapse were studied compared with control data for 6R cartridges (Nicol and Meinertzhagen, '82). The synapse population size and distribution within five depth levels of the lamina is, on average, approximately constant for all receptor terminals whether from 6R, 7R, or 8R cartridges. The overall determinant of synapse frequency is therefore presynaptic. Small (5-6%) average decreases in synapse frequency per receptor in 7R and 8R cartridges compared with 6R co-vary with similar decreases in membrane area, each synapse occupying a patch of membrane of similar area in all cases. The tetradic postsynaptic composition of synapses was also similar in all cases. Because of the augmented synaptic input to the postsynaptic neurons, a morphometric analysis was undertaken of two (L1 and L2), which receive input as a pair from every synapse. There is the same dendrite number (about 180) in 8R L1/L2 as in 6R L1/L2 but they have different branching patterns, conforming to the different number and configuration of receptor terminals. Thus in an 8R cartridge each terminal is serviced by a comb of fewer dendrites, but each dendrite is longer, fatter, and services more synapses. The area of L1/L2 dendritic membrane exposed is increased, compared with 6R cartridges, in proportion with the number of synapses it participates at postsynaptically, so that all dendrites (6R and 8R) allocate the same mean area (about 0.55 micrometer2) of postsynaptic membrane per synapse.

Animals↗
PubMed1995

Inhibitory axoaxonal and neuromuscular synapses in the crayfish opener muscle: membrane definition and ultrastructure.

The specific inhibitory motoneuron to the crayfish (Procambarus clarkii) opener muscle provides neuromuscular synapses to the muscle fibers and axoaxonal synapses to the excitatory motor nerve terminals. Freeze fracture of the membrane in both types of synapses show that the presynaptic active zone consists of clusters of large particles (putative calcium channels), which are often encircled by large depressions representing fused synaptic vesicles on the internal leaflet or P face of the presynaptic membrane. Corresponding pits and protrusions mark the external leaflet or E face of the presynaptic membrane. The postsynaptic receptor-bearing surface, characterized for neuromuscular synapses only, consists of rows of particles on both leaflets of the muscle membrane. The organization differs from that seen at excitatory synapses where particles occur only on the E-face leaflet. Serial thin sections of nerve terminals reveal that neuromuscular synapses are significantly larger in proximal fibers than in their central counterparts and support a greater number of presynaptic dense bars (active zones). Axoaxonal synapses also show regional differences; almost three times as many occur in the proximal region compared with the central region. Most synapses possess a single dense bar. The majority of synapses formed by the inhibitory axon are neuromuscular; a minority are axoaxonal. The latter occur in various locations along the excitatory nerve terminals as well as on branches of the axon itself. This preterminal or "off-shore" location could act to cut off entire populations of excitatory synapses or reduce the amplitude of the preterminal action potential.

Animals↗
PubMed2005

Multifocal structure of the T cell - dendritic cell synapse.

The structure of immunological synapses formed between murine naive T cells and mature dendritic cells has been subjected to a quantitative analysis. Immunofluorescence images of synapses formed in the absence of antigen show a diffuse synaptic accumulation of CD3 and LFA-1. In electron microscopy, these antigen-free synapses present a number of tight appositions (cleft size approximately 15 nm), all along the synapse. These tight appositions cover a significantly larger surface fraction of antigen-dependent synapses. In immunofluorescence, antigen-dependent synapses show multiple patches of CD3 and LFA-1 with a variable overlap. A similar distribution is observed for PKCtheta and talin. A concentric organization characteristic of prototypical synapses is rarely observed, even when dendritic cells are paralyzed by cytoskeletal poisons. In T-DC synapses, the interaction surface is composed of several tens of submicronic contact spots, with no large-scale segregation of CD3 and LFA-1. As a comparison, in T-B synapses, a central cluster of CD3 is frequently observed by immunofluorescence, and electron microscopy reveals a central tight apposition. Our data show that it is inappropriate to consider the concentric structure as a "mature synapse" and multifocal structures as immature.

Animals↗