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PubMed1983

The formation and maturation of synapses in the visual cortex of the rat. II. Quantitative analysis.

We have examined quantitatively the formation and maturation of synapses in the visual cortex of the rat. The density of the total number of synapses (synapses per 100 micron2 neuropil) as well as the densities of Gray's type I and type II contacts were estimated from photographic montages of coronal strips of visual cortex from rats of various postnatal ages. Histograms of synaptic density as a function of depth were prepared, and the mean values of the postsynaptic density length and vesicle number per terminal were estimated for the two synapse types at each age examined. During the first few days of life, synapses were concentrated in the subplate region. By the latter part of the second postnatal week they were present throughout the cortex and an adult-like distribution, in which the highest densities were present in the superficial layers, was achieved by day 14. The postsynaptic density length of the type I synapses remained relatively unchanged during development but that of the type II synapses was more variable. Specifically, it was significantly longer during the second and third postnatal weeks compared to earlier ages and to adult values. The mean number of vesicles per terminal for the two synapse types increased with age until day 28. Subsequently, it only increased slightly between days 28 and 90 for the type I synapses but decreased significantly for the type II synaptic contacts. At all ages examined, type I synapses formed the majority of synaptic contacts. The developmental pattern appeared to differ for the two synapse types. The density of type I synapses increased continuously during the first three weeks and achieved a mean value close to that of adult animals by day 20. In contrast, the density of type II synapses did not increase significantly until day 6, increased dramatically in the second and third postnatal weeks, and then declined markedly between days 20 and 90. The observed decrease in the density of type II synaptic contacts is a clear example of synapse elimination in the visual cortex.

Age Factors↗
PubMed1985

Synapse elimination in the developing visual cortex: a morphometric analysis in normal and dark-reared cats.

The elimination of synapses from developing visual cortex, occurring after day 70 in cat, is thought to result from competition among redundant axons innervating area 17. The dependence of this elimination on visual experience was tested by comparing normal cats at 70 and 220 days of age with littermates dark-reared from day 70 to day 220. Thickness of all cortical laminae, numerical density (NV) of neurons in layers I-III and NV of synapses in layers I-III were measured in two regions of area 17, corresponding to central (0-5 degrees) and peripheral (15-20 degrees) representations of the binocular visual field. In the central region, normal development was characterized by a 25% decrease in thickness of layers I-III with a corresponding increase in the NV of neurons. The NV of synapses in layer I decreased by 29%, with a 52% decrease in the number of synapses under one mm2 of pial surface. In layers II-III the NV of synapses decreased by 31%, with a 46% decrease in the number of synapses under 1 mm2 of pial surface. These developmental changes were unaffected by dark-rearing. In the peripheral region, normal cats exhibited no significant changes in laminar thickness or in NV of synapses, although the number of synapses under 1 mm2 of pial surface decreased by 25% in layer I and by 18% in layers II-III. In dark-reared cats the thickness of layers I-III decreased by 26% with a corresponding increase in the NV of neurons. The NV of synapses in layer I decreased by 18% and the number of synapses under 1 mm2 of pial surface by 51%. In layers II-III the NV of synapses decreased by 22% and the number of synapses under 1 mm2 of pial surface by 39%. Thus, in normal development the loss of synapses is greater from central than from peripheral representations of area 17. Dark-rearing does not alter the elimination of synapses in central cortex, but accelerates this loss in peripheral cortex.

Animals↗
PubMed1994

5-hydroxydopamine-labeled dopaminergic axons: three-dimensional reconstructions of axons, synapses and postsynaptic targets in rat neostriatum.

Previous studies employing 5-hydroxydopamine to identify nigrostriatal dopaminergic axons and their synapses found that labeled axons made few synapses or that asymmetric contacts predominated. In contrast, recent studies using tyrosine hydroxylase or dopamine antibody techniques indicate that presumed dopaminergic axons form small symmetric contacts. We re-examined 5-hydroxydopamine-labeled material from the rat neostriatum using serial three-dimensional reconstruction techniques to characterize the morphology of labeled axons, synapses and postsynaptic targets. This ultrastructural analysis revealed a class of heavily labeled axons that are small (0.06-1.5 microns in diameter) and lack large varicosities. These axons form small (0.011-0.09 microns 2), en passant, symmetric synapses, mainly onto dendritic spines and spiny dendritic shafts and, in some cases, onto aspiny dendritic segments near branch points. The sites of these synapses along the axon appeared unrelated to the locations of axonal enlargements, suggesting that counting varicosities may not be an accurate indication of the extent of dopaminergic innervation in the neostriatum. The characteristics of these 5-hydroxydopamine-labeled elements correspond in all respects to axons and synapses identified as dopaminergic by immunohistochemistry in previous studies. In tissue in which all labeled and unlabeled synapses were classified, approximately 9% of all synapses were identified as dopaminergic by this type of label. Three-dimensional reconstructions provided additional insight concerning the interaction of dopaminergic afferents with postsynaptic striatal targets and their relation to other afferents to these neurons. They reveal that a short, unbranched dopaminergic axonal segment can make multiple synapses onto dendritic spines, shafts and branch points of one or more dendrites. In addition, one dendrite can receive contacts from several labeled axons. Dopamine synapses onto spines are always associated with unlabeled, asymmetric synapses onto the same spine. Synapses of various morphologies with a distinctly different, lighter form of labeling were much rarer, and may represent other aminergic afferents to the neostriatum. The presence of this second form of label in earlier 5-hydroxydopamine studies may have contributed to the long-standing controversy over the appearance of dopaminergic synapses examined by different techniques. Our results help to resolve this controversy and confirm that the nigrostriatal projection makes small symmetric synapses with a variety of striatal targets.

Animals↗
PubMed2004

Quantification of synapse formation and maintenance in vivo in the absence of synaptic release.

Outgrowing axons in the developing nervous system secrete neurotransmitters and neuromodulatory substances, which is considered to stimulate synaptogenesis. However, some synapses develop independent of presynaptic secretion. To investigate the role of secretion in synapse formation and maintenance in vivo, we quantified synapses and their morphology in the neocortical marginal zone of munc18-1 deficient mice which lack both evoked and spontaneous secretion [Science 287 (2000) 864]. Histochemical analyses at embryonic day 18 (E18) showed that the overall organization of the neocortex and the number of cells were similar in mutants and controls. Western blot analysis revealed equal concentrations of pre- and post-synaptic marker proteins in mutants and controls and immunocytochemical analyses indicated that these markers were targeted to the neuropil of the synaptic layer in the mutant neocortex. Electron microscopy revealed that at E16 immature synapses had formed both in mutants and controls. These synapses had a similar synapse diameter, active zone length and contained similar amounts of synaptic vesicles, which were immuno-positive for two synaptic vesicle markers. However, these synapses were three times less abundant in the mutant. Two days later, E18, synapses in the controls had more total and docked vesicles, but not in the mutant. Furthermore, synapses were now five times less abundant in the mutant. In both mutant and controls, synapse-like structures were observed with irregular shaped vesicles on both sides of the synaptic cleft. These 'multivesicular structures' were immuno-positive for synaptic vesicle markers and were four times more abundant in the mutant. We conclude that in the absence of presynaptic secretion immature synapses with a normal morphology form, but fewer in number. These secretion-deficient synapses might fail to mature and instead give rise to multivesicular structures. These two observations suggest that secretion of neurotransmitters and neuromodulatory substances is required for synapse maintenance, not for synaptogenesis. Multivesicular structures may develop out of unstable synapses.

Animals↗
PubMed2001

Postnatal differentiation of unipolar brush cells and mossy fiber-unipolar brush cell synapses in rat cerebellum.

The unipolar brush cells are excitatory, cerebellar granular layer interneurons that receive mossy fiber input on their dendritic brushes in the form of a giant glutamatergic synapse. We investigated the postnatal development of the brush of the unipolar brush cell in lobules IX and X by light microscopy and defined the maturation of mossy fiber-unipolar brush cell synapses and mossy fiber-granule cell synapses by electron microscopy using calretinin immunocytochemistry to identify unipolar brush cells. During the first postnatal week, unipolar brush cells possessed one or two short, branched dendrites. The brush differentiated primarily during the successive 21 postnatal (P) days, during which it underwent progressive maturation. This developmental process was subdivided into stages 1-4, which were descriptively termed protodendritic unipolar brush cell (P2-12), filopodial brush (P12-16), intermediate brush (P16-21), and dendriolar brush (P21-28) stages. Electron microscopic measurements of individual mossy fiber-unipolar brush cell and mossy fiber-granule cell synaptic junctions were made at P12, 16, 21, and 28. While the average length of mossy fiber-unipolar brush cell synapses increased during development, that of mossy fiber-granule cell synapses decreased. Comparisons of the lengths of mossy fiber-unipolar brush cell and mossy fiber-granule cell synapses demonstrated that mossy fiber-unipolar brush cell synapses were longer on average than mossy fiber-granule cell synapses for all ages. Frequency distribution histograms also showed that the percentage of mossy fiber-unipolar brush cell synapses longer than 0.5 microm was lower in the pooled P12-P16 groups than in the pooled P21-P28 groups (8 versus 20%). In contrast, mossy fiber-granule cell synapses longer than 0.5 microm were a small minority at P12, 16, and 21, and occurred rarely at P28. The present study indicates that mossy fiber-unipolar brush cell synapses increase in length with the differentiation of the brush dendrioles, while that of mossy fiber-granule cell synapses decrease with differentiation of the granule cell dendritic claws. The finding that mossy fiber-unipolar brush cell synapses were generally longer than mossy fiber-granule cell synapses may indicate that the properties of the postsynaptic targets play a major role in shaping synaptic appositions within cerebellar glomeruli.

Aging↗
PubMed1977

The formation and regression of synapses during the re-innervation of axolotl striated muscles.

1. A study has been made of the formation and regression of synapses formed by spinal nerves 16 and 17 in axolotl hind-limb flexor muscles following the severing of nerve 16, using histological, ultrastructural and electrophysiological techniques. 2. Axolotl hind-limb flexor myofibres possessed 'en plaque' end-plates from either spinal nerve 16 or 17 or both at intervals of about 1000 micronm along their length; the myofibre's length constant was about 700 micronm allowing electrophysiological observations of at least two of these synapses during a single impalement; transmitter release at these synapses could be described by binomial statistics and in a given set of ionic conditions the binomial statistic parameter n was directly proportional to the size of the nerve terminals whilst the binomial statistic parameter p was invariant to changes in nerve terminal size. 3. The distribution of synapses formed by spinal nerves 16 and 17 in different sectors of the axolotl hind-limb flexor muscles was determined from a study of evoked end-plate potentials; the middle and proximal sectors of the flexor muscles contained myofibres which received an innervation from nerve 16 only, whereas the sectors surrounding these contained myofibres innervated either by nerve 16 or nerve 17 or by both nerves. 4. Six days following the severing of spinal nerve 16, evoked transmitter release from the synapses formed by this nerve had failed; transmission was subsequently recorded at a few synapses formed by nerve 17 in the middle and proximal sectors of the flexor muscles which are not normally innervated by this nerve and these synapses had a low n; during the succeeding four weeks the value of n at the synapses increased to a size about 70% that of the terminals normally formed by nerve 16 at these sites. 5. Four weeks after severing nerve 16, myofibres which possessed synapses formed by nerve 17 also possessed synapses from re-innervating nerve 16 and these were sometimes formed at the same synaptic sites as those occupied by nerve 17. 6. In the subsequent sixteen weeks, the n value of synapses formed by nerve 17 declined whilst the n values of synapses formed by re-innervating nerve 16 on the same myofibres matured to their control size. 7. It is suggested that on severing nerve 16 collateral sprouting of nearby intact nerve 17 occurs and these collateral sprouts innervate the denervated synaptic sites, although the sprouts arenot as well matched to the denervated synaptic sites as are the original nerve terminals; thus if nerve 16 returns it preferentially forms synapses at its original synaptic sites, and the collateral synapses formed by nerve 17 regress.

Ambystoma↗
PubMed2005

Mechanisms of target-cell specific short-term plasticity at Schaffer collateral synapses onto interneurones versus pyramidal cells in juvenile rats.

Although it is presynaptic, short-term plasticity has been shown at some synapses to depend upon the postsynaptic cell type. Previous studies have reported conflicting results as to whether Schaffer collateral axons have target-cell specific short-term plasticity. Here we investigate in detail the short-term dynamics of Schaffer collateral excitatory synapses onto CA1 stratum radiatum interneurones versus pyramidal cells in acute hippocampal slices from juvenile rats. In response to three stimulus protocols that invoke different forms of short-term plasticity, we find differences in some but not all forms of presynaptic short-term plasticity, and heterogeneity in the short term plasticity of synapses onto interneurones. Excitatory synapses onto the majority of interneurones had less paired-pulse facilitation than synapses onto pyramidal cells across a range of interpulse intervals (20-200 ms). Unlike synapses onto pyramidal cells, synapses onto most interneurones had very little facilitation in response to short high-frequency trains of five pulses at 5, 10 and 20 Hz, and depressed during trains at 50 Hz. However, the amount of high-frequency depression was not different between synapses onto pyramidal cells versus the majority of interneurones at steady state during 2-10 Hz trains. In addition, a small subset of interneurones (approximately 15%) had paired-pulse depression rather than paired-pulse facilitation, showed only depression in response to the high-frequency five pulse trains, and had more steady-state high-frequency depression than synapses onto pyramidal cells or the majority of interneurones. To investigate possible mechanisms for these differences in short-term plasticity, we developed a mechanistic mathematical model of neurotransmitter release that explicitly explores the contributions to different forms of short-term plasticity of the readily releasable vesicle pool size, release probability per vesicle, calcium-dependent facilitation, synapse inactivation following release, and calcium-dependent recovery from inactivation. Our model fits the responses of each of the three cell groups to the three different stimulus protocols with only two parameters that differ with cell group. The model predicts that the differences in short-term plasticity between synapses onto CA1 pyramidal cells and stratum radiatum interneurones are due to a higher initial release probability per vesicle and larger readily releasable vesicle pool size at synapses onto interneurones, resulting in a higher initial release probability. By measuring the rate of block of NMDA receptors by the open channel blocker MK-801, we confirmed that the initial release probability is greater at synapses onto interneurones versus pyramidal cells. This provides a mechanism by which both the initial strength and the short-term dynamics of Schaffer collateral excitatory synapses are regulated by their postsynaptic target cell.

Action Potentials↗
PubMed1998

Stability in synapse number and size at 2 hr after long-term potentiation in hippocampal area CA1.

Long-term potentiation (LTP) is an important model for examining synaptic mechanisms of learning and memory. A key question is whether the enhanced synaptic transmission occurring with LTP involves the addition of new synapses, the enlargement of existing synapses, or a redistribution in synaptic weight among synapses. Two experimental designs were used to address this question. In the first experimental design three conditions were evaluated across hippocampal slices maintained in vitro, including slices with LTP analyzed at 2 hr post-tetanus, slices tetanized in the presence of APV, and control slices receiving test stimulation only. In the second experimental design independent LTP and control (low-frequency stimulation) sites were examined. Synapse density was estimated by an unbiased volume sampling procedure. Synapse size was computed by three-dimensional reconstruction from serial electron microscopy (EM). Serial EM also was used to compute synapse number per unit length of dendrite. In both experimental designs there were no significant effects of LTP on total synapse number, on the distribution of different types of synapses (thin, mushroom, stubby, or branched dendritic spines and macular, perforated, or segmented postsynaptic densities), on the frequency of shaft synapses, nor on the relative proportion of single or multiple synapse axonal boutons. There was also no increase in synapse size. These results suggest that LTP does not cause an overall formation of new synapses nor an enlargement of synapses at 2 hr post-tetanus in hippocampal area CA1, and these results support the hypothesis that LTP could involve a redistribution of synaptic weights among existing synapses.

Animals↗
PubMed1999

Distribution of synaptic vesicle proteins in the mammalian retina identifies obligatory and facultative components of ribbon synapses.

The mammalian retina contains two synaptic layers. The outer plexiform layer (OPL) is primarily composed of ribbon synapses while the inner plexiform layer (IPL) comprises largely conventional synapses. In presynaptic terminals of ribbon synapses, electron-dense projections called ribbons are present at the synaptic plasma membranes. Ribbons bind synaptic vesicles and guide them to the synaptic membrane for fusion. In this manner, ribbons are thought to accelerate the delivery of vesicles for continuous exocytosis. In recent years, a large number of synaptic proteins has been described but it is not known if these protein colocalize in the same types of synapses. In previous studies, several proteins essential for synaptic function were not detected in ribbon synapses, suggesting that the mechanism of synaptic vesicle exocytosis may be very different in ribbon and conventional synapses. Using confocal laser scanning microscopy, we have now systematically investigated the protein composition of ribbon synapses. Our results show that, of the 19 synaptic proteins investigated, all except synapsin and rabphilin are obligatorily present in ribbon synapses. For example, rab3 which was reported to be absent from ribbon synapses, was found in bovine, rat and mouse ribbon synapses using multiple independent antibodies. In addition, we found staining in these synapses for PSD-95 and NMDA receptors, which suggested a similar design for the postsynaptic component in ribbon and conventional synapses. Our data show that ribbon synapses are more conventional in composition than reported, that most synaptic proteins are colocalized to the same type of synapse, and that synapsin and rabphilin are likely to be dispensible for basic synaptic functions.

Animals↗
PubMed1975

The development of synapses in the visual system of the cat.

Synapses have been counted by electron microscopy and neurones by light microscopy through the depth of the visual cortex in a series of cats from 37 days gestation to adulthood. A few definite synapses are present as early as three weeks before birth, but there is then a latent period of four weeks before synapses increase rapidly in number 8-37 days after birth. The synapses occur just above and just below the cell plate at first, but in the adult cat they become evenly distributed in the depth of the cortex. The gradual separation of neurones by neuropil during development precedes a parallel increase in the density of synapses by about one week. The average number of synapses associated with one neurone rises to a peak of about 13,000 at seven weeks after birth. The densities of synapses and of neurones subsequently fall to slightly lower values in adult cats as the glial cells continue to develop. The timing of synaptic development in the visual cortex has been compared quantitatively with that in the L. G. N. and qualitatively with synaptogenesis in the retina. Synapses develop in the L. G. N. and cortex in a parallel fashion, and the L. G. N. precedes the cortex by a short interval of about two days. In the cell plate of the retina a few receptor synapses are present nine days before birth. Inner plexiform synapses are aslo present at this time, but ribbon-containing synapses do not appear until birth. Very few receptors possess outer segments with discs at birth, but five days later disc-bearing outer segments have developed. Thus synaptic development starts before afferent impulses can enter the visual system, but the main increase in synapses in the L. G. N. and cortex takes place four weeks after the start of synapse formation while the visual system is being used.

Age Factors↗
PubMed1985

The distribution of synapses on the two fields of neurites of spiking local interneurones in the locust.

Spiking local interneurones in the metathoracic ganglion of the locust have two fields of neuropilar branches linked by a single process. One, with numerous fine neurites of relatively uniform diameter, is in a ventral area of neuropile where the afferents from hairs on a hind leg also terminate. The other, with sparser and varicose neurites, is in a more dorsal area of neuropile where the motor neurones of the leg muscles have many neurites. Physiological studies have shown that these interneurones receive direct inputs from some hair afferents and in turn synapse directly upon some leg motor neurones (Burrows and Siegler, '82; Siegler and Burrows, '83). The distribution of synapses in these two fields was revealed by injecting HRP intracellularly into an interneurone following its physiological characterization. In the ventral field, the majority of synapses are input synapses. Many are from profiles with round agranular vesicles of similar diameter to those of known afferents. Other presynaptic profiles contain pleomorphic agranular, or large round granular, vesicles. There are also some output synapses, each with only a small population of vesicles. Most input synapses are made onto small-diameter neurites, whereas the majority of outputs are made from the larger-diameter neurites. In the dorsal field, the majority of synapses are output synapses. They are made from vesicle-filled varicosities onto postsynaptic profiles of small diameter. A single varicosity can be the site of many output synapses. Input synapses are few in number, but occur close to the output synapses. The absence of varicosities in the ventral field cannot therefore be correlated with a lack of output synapses and while the dorsal varicosities can be the sites of output, they can also receive input synapses.

Action Potentials↗
PubMed1988

Ultrastructural characterization of the synapses of the crossed temporodentate pathway in rats.

The present study was undertaken to define the ultrastructure of synapses of the crossed temporodentate pathway from the entorhinal cortex to the contralateral dentate gyrus and to compare the synapses of the sparse crossed pathway with those of the massive ipsilateral temporodentate pathway. The synapses of the crossed pathway were identified by using EM degeneration and EM autoradiographic techniques. For the degeneration studies, adult male Sprague-Dawley rats were killed 1, 2, or 4 days following a unilateral entorhinal cortex lesion and prepared for electron microscopy. To identify the synapses by using autoradiographic techniques, four animals received injections of 3H-proline into the entorhinal cortex, were allowed to survive for 3 days, and were prepared for EM autoradiography. Degenerating synapses of the crossed pathway that were found in the molecular layer of the dentate gyrus contralateral to a lesion formed asymmetric synapses on spines and possessed presynaptic organelles indistinguishable from synapses of the ipsilateral temporodentate pathway. The number of degenerating synapses was very low at all survival intervals (14.80 degenerating synapses/10,000 microns2 at 1 day postlesion and 1.95 degenerating synapses/10,000 microns2 at 2 days postlesion); no degenerating synapses were found at 4 days postlesion. Ninety-eight percent of the degenerating synapses found at 1 day postlesion exhibited electron-lucent degeneration. At 2 days postlesion 83% of the degenerating synapses in the dorsal blade and 18% of those in the ventral blade showed lucent degeneration; the remainder were electron dense. EM autoradiography confirmed the degeneration studies in terms of the type of terminals that were labeled and suggested that the density of the crossed pathway was higher than the degeneration results implied. We conclude that synapses of the crossed temporodentate pathway have a similar ultrastructure to synapses of the ipsilateral temporodentate pathway but exhibit a rapid form of degeneration such that they disappear very rapidly following the lesion.

Animals↗
PubMed1989

Ultrastructural analysis of the development and maturation of synapses and subsynaptic structures in the ectostriatum of the zebra finch.

The development of synapses and subsynaptic features in the neuropil of the ectostriatum, a visual projection area in birds, was examined ultrastructurally at 5, 10, 20, and 100 days posthatching. The maturation of the synaptic complex is accompanied by a variety of different dynamic processes. The number of synapses in ectostriatum and the number of specific synaptic types vary with age as does the constellation of subsynaptic structures. At day 5, before eye opening, the total number of synapses is 16% of the adult value. These synapses, unlike synapses seen at maturity, have indistinct synaptic contact zones and generally are associated with few synaptic vesicles. Synapse number increases continuously until 20 days of age, paralleled by a steady increase of the observed brain volume. The largest increase in synapse number takes place during the time of eye opening (i.e., between 5 and 10 days). This increase is mainly due to an increase of asymmetric synapses, the most common type in the neuropil of ectostriatum (90% of the synapse population). At day 20 the number of synapses has reached its maximum and remains high in adulthood. Synapses on spines are more prominent in younger animals than in adults. The percentage of presynaptic terminals involved in synaptic contact with more than one postsynaptic element (multiple synapses) shows a significant reduction from 12% to 4% early in development (between days 10 and 20). Presynaptic terminal size and postsynaptic density (PSD) length increase until 20 days of age. From day 20 to adulthood the PSD shows a 10% reduction in contact length, and the presynaptic terminal further increases in size by 27%. Therefore, the pre- and postsynaptic structures described above continue to develop after the number of synapses remains constant.

Animals↗
PubMed1979

Development of neocortical circuitry: quantitative ultrastructural analysis of putative monoaminergic synapses.

The distribution, numbers and morphology of presumed monoaminergic (MA) synapses were examined in somatosensory cortex of neonatal rats and mice (newborn to 16 days of age). MA synapses were identified using an ultrastructural cytochemical marker, 5-hydroxydopamine (5-OHDA), which results in the appearance of small granular vesicles (SGV) in their presynaptic terminals. From birth to 7 days of age, 20--30% of all synapses sampled in somatosensory cortex contain SGVs. However, few SGV synapses are seen in 8-day-old cortex and by 12 days of age, SGVs are no longer detectable in cortex. A specific laminar distribution for these SGV synapses -- which is distinct from the overall synaptic distribution -- is first seen at 3 days of age and is essentially unchanged until 7 days postnatally. During this entire period, the SGV synapses predominate in the primordium of layer IV, where they account for 50--70% of all synapses. Morphometric analysis of SGV synapses indicates that there are differences in junctional symmetry, vesicle shape and configuration of the contact zone between SGV and non-SGV synapses, as well as between SGV synapses themselves in the various cortical layers. The laminar distribution and morphological characteristics of SGV synapses suggest that the MA projection to neocortex exhibits a high degree of spatial specificity during its ingrowth. Also, the relatively high proportion of SGV synapses in the first postnatal week may reflect a potent influence exerted by the MA inputs on immature neocortex. The decreased numerical density of SGV synapses after 7 days of age is probably due to the development of the blood-brain barrier to 5-OHDA.

Aging↗
PubMed1986

Outgoing synapses of small granule-containing cells in the rat superior cervical ganglion after post-ganglionic axotomy.

Small granule-containing cells are intrinsic and interneurone-like in the rat superior cervical ganglion, being innervated by preganglionic axons and giving outgoing synapses of asymmetrical type to the principal neurones. A quantitative ultrastructural investigation has been made of the effect on these outgoing synapses of axotomy of the major post-ganglionic nerve trunks 18.5 h-390 days previously. Cutting, or cutting and ligating, the internal and external carotid nerves 2-3 mm from the ganglion in rats aged 1.5-5.5 months resulted in a statistically significant mean loss of up to 85% of the asymmetrical synapses given by small granule-containing cells in the injured ganglion. The reduction of synapses was maximal 5-9 days post-operatively, and thereafter the incidence of synapses showed significant signs of progressive recovery. The time course and magnitude of the change in incidence of these synapses resembled those found earlier (Matthews & Nelson, 1975) for the loss of preganglionic synapses to principal neurones in the same ganglia, and after an identical post-ganglionic lesion. Control experiments showed that there was no loss of outgoing synapses from the small granule-containing cells as a result of surgical stress or of simple ageing. Older rats (5.5 and 13 months) showed a small but significant increase in the incidence of these synapses. Unilateral post-ganglionic axotomy produced the same reaction in the injured ganglia as did bilateral lesions. Uninjured ganglia contralateral to unilateral axotomies, however, also showed some deficit of outgoing synapses from small granule-containing cells, but this was slight, amounting to 9.9% over-all in comparison to normal values in young rats, and this difference did not reach statistical significance. Cutting the cervical sympathetic trunk to produce preganglionic denervation 2 days before surgical removal of ganglia for analysis did not alter the incidence of outgoing synapses of the small granule-containing cells, either in ganglia post-ganglionically axotomized 5-128 days earlier or in contralateral ganglia, indicating that at no stage was any significant proportion of these synapses given to preganglionic axons. These findings suggest that most of the outgoing synapses from the intra-ganglionic small granule-containing cells are directed to principal neurones whose axons leave with the injured branches, the internal and external carotid nerves.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2006

Distinct transmitter release properties determine differences in short-term plasticity at functional and silent synapses.

Recent evidence suggests that functional and silent synapses are not only postsynaptically different but also presynaptically distinct. The presynaptic differences may be of functional importance in memory formation because a proposed mechanism for long-term potentiation is the conversion of silent synapses into functional ones. However, there is little direct experimentally evidence of these differences. We have investigated the transmitter release properties of functional and silent Schaffer collateral synapses and show that on the average functional synapses displayed a lower percentage of failures and higher excitatory postsynaptic current (EPSC) amplitudes than silent synapses at +60 mV. Moreover, functional but not silent synapses show paired-pulse facilitation (PPF) at +60 mV and thus presynaptic short-term plasticity will be distinct in the two types of synapse. We examined whether intraterminal endoplasmic reticulum Ca2+ stores influenced the release properties of these synapses. Ryanodine (100 microM) and thapsigargin (1 microM) increased the percentage of failures and decreased both the EPSC amplitude and PPF in functional synapses. Caffeine (10 mM) had the opposite effects. In contrast, silent synapses were insensitive to both ryanodine and caffeine. Hence we have identified differences in the release properties of functional and silent synapses, suggesting that synaptic terminals of functional synapses express regulatory molecular mechanisms that are absent in silent synapses.

Animals↗
PubMed2000

Stability and variability of synapses in the adult molluskan CNS.

Synaptic transmission was examined between identified neurons in the central nervous system (CNS) of the freshwater mollusk, Lymnaea stagnalis. Four identified neurons were used: Right Pedal Dorsal one (RPeD1; a dopaminergic respiratory interneuron), Visceral Dorsal two and three (VD2/3), and Visceral Dorsal four (VD4; a cardiorespiratory interneuron). Neuron RPeD1 synapses onto both VD2/3 and VD4, while VD4 makes a reciprocal synapse onto RPeD1. When compared from animal to animal, the connections were variable in sign. Previously, we demonstrated that, in a given animal, the RPeD1 --> VD4 synapse could be either inhibitory, biphasic, or undetectable. The present study now expands this concept of variability by showing that the RPeD1 --> VD2/3 synapse was either excitatory or undetectable from animal to animal, while the synapse from VD4 to RPeD1 was observed as inhibitory, biphasic, depolarizing, excitatory, or undetectable. Next, we used 1-day organ culture to determine if the variability observed between animals is a product of ongoing change to the sign of these identified synapses and whether or not the extent of change could be influenced by the culture conditions. Changes to the sign of transmission occurred within minutes and, more commonly, after 24-h organ culture. All three synapses were investigated before and after 1-day organ culture, in either defined medium (DM) or brain-conditioned medium (CM). Regardless of culture conditions, the RPeD1 --> VD2/3 synapse showed no change of sign, i.e., it was relatively stable. However, the synapses between RPeD1 and VD4 did change sign, and when cultured in CM, the VD4 --> RPeD1 synapse changed significantly more than in DM. These data indicate that variability of some synapses reflects changes at these synapses. This is the first report that specific synapses in an adult CNS can change sign, and that the sign of transmission can be modulated by environmental conditions.

Animals↗
PubMed2000

Different extrinsic trophic factors regulate neurite outgrowth and synapse formation between identified Lymnaea neurons.

The requirement for trophic factors in neurite outgrowth is well established, though their role in synapse formation is yet to be determined. Moreover, the issue of whether the trophic factors mediating neurite outgrowth are also responsible for synapse specification has not yet been resolved. To test whether trophic factors mediating neurite outgrowth and synapse formation between identified neurons are conserved in two molluscan species and whether these developmental processes are differentially regulated by different trophic factors, we used soma-soma and neurite-neurite synapses between identified Lymnaea neurons. We demonstrate here that the trophic factors present in Aplysia hemolymph, although sufficient to induce neurite outgrowth from Lymnaea neurons, do not promote specific synapse formation between excitatory partners. Specifically, the identified presynaptic neuron visceral dorsal 4 (VD4) and postsynaptic neuron left pedal dorsal 1 (LPeD1) were either paired in a soma-soma configuration or plated individually to allow neuritic contacts. Cells were cultured in either Lymnaea brain-conditioned medium (CM) or on poly-L-lysine dishes that were pretreated with Aplysia hemolymph (ApHM), but contained only Lymnaea defined medium (DM; does not promote neurite outgrowth). In ApHM-coated dishes containing DM, Lymnaea neurons exhibited extensive neurite outgrowth, but appropriate excitatory synapses failed to develop between the cells. Instead, inappropriate reciprocal inhibitory synapses formed between VD4 and LPeD1. Similar inappropriate inhibitory synapses were observed in Aplysia hemolymph-pretreated dishes that contained dialyzed Aplysia hemolymph. These inhibitory synapses were novel and inappropriate, because they do not exist in vivo. A receptor tyrosine kinase inhibitor (Lavendustin A) blocked neurite outgrowth induced by both Lymnaea CM and ApHM. However, it did not affect inappropriate inhibitory synapse formation between the neurons. These data demonstrate that neurite outgrowth but not inappropriate inhibitory synapse formation involves receptor tyrosine kinases. Together, our data provide direct evidence that trophic factors required for neurite outgrowth are conserved among two different molluscan species, and that neurite extension and synapse specification between excitatory partners are likely mediated by different trophic factors.

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