Synaptic Contact Zones Research Articles

Synaptic Relations of GABAergic Neurons in the Area Postrema

gamma-Aminobutyric acid (GABA)-like immunoreactive neuronal profiles and their synaptic relations in the area postrema of the rat were studied by ultrastructural immunocytochemistry using an antibody directed against GABA. GABA-like immunoreactive (GABA-LI) perikarya and dendrites usually received synaptic inputs from nonimmunoreactive axon terminals. These synaptic contact zones were mostly asymmetrical. Conversely, GABA-LI axon terminals were found to make synapses with nonimmunoreactive perikarya and dendrites, usually of the symmetrical type. Furthermore, GABA-LI axon terminals in synaptic contact with GABA-LI perikarya and dendrites were sometimes found. Although some GABA-LI axon terminals were in close vicinity of other nonimmunoreactive axon terminals, no clear synaptic contacts could be found. On the other hand, GABA-LI profiles could be found close to the capillaries, although they were always separated by a thin layer of glial processes. The above results suggest that the GABAergic neuron receives information from both the circulating blood and other neurons and then performs its depressor function through other neurons.

Morphological plasticity of synaptic mitochondria during aging

A morphometric investigation has been carried out on the synaptic mitochondria of cerebellar glomeruli in young, adult and old rats by means of a computer-assisted image analysis technique. Mitochondrial volume density ( V v), numerical density ( N v), average volume ( V) and average length (Skeleton= S k) were investigated in tissue samples fixed, embedded and sectioned according to conventional electron microscopic methods. V v was unchanged in the three groups of age taken into account. N v was significantly increased in adult vs. young animals, whereas it was decreased in the old group as compared to both the other two groups investigated. V and S k showed the same age-dependent changes: they significantly decreased in the adult vs. the young and the old groups of rats while increased significantly in the old rats vs. both the adult and young animals. A percentage distribution of S k demonstrated that in the old group 20.6% of the population of synaptic mitochondria account for elongated organelles ( 5 μm) as compared to 8.6% and 5.3% in young and adult animals, respectively. The present findings match the changes previously reported by us on the ultrastructure of synaptic contact zones both in rats and human beings, and support the idea of an age-dependent dynamic adaptation in the morphology of synaptic mitochondria to cope with the metabolic needs of the pattern of synaptic connectivity they subserve.

Effects of differential rearing on the structure of perforated synapses in the granule cell layer of the rat's accessory olfactory bulb

The effects of differential rearing on synaptic morphology in the granule cell layer of the accessory olfactory bulb (AOB) were examined in adult rats. Forty-day-old male rats were housed in one of three ways: individually (isolated condition, IC); with four males per cage (unisexual condition, UC); or with two males and two females per cage (social condition, SC). After 2 months, the animals were killed for electron microscopy. Two types of synapses were classified: (1) perforated synapses, which are characterized by discontinuities in their postsynaptic thickenings, and (2) non-perforated synapses. The length of the synaptic contact zone as well as the area and the length of the perimeter of both the pre- and postsynaptic terminals were measured in each observed synapse. For perforated synapses, the length of the synaptic contact zone was significantly greater in the UC and the SC than in the IC. For the presynaptic terminals of perforated synapses, the area was greater in the UC and the SC than in the IC, and the length of the perimeter was greater in the UC than in the IC. In contrast, there was no difference in the area and the length of the perimeter among the three groups for postsynaptic terminals. For non-perforated synapses, there was no statistically significant difference in either the area or the length of the perimeter of pre- and postsynaptic terminals among the three experimental groups, although the length of the synaptic contact zone was greater in the SC than in the IC. These results demonstrated that exposure to different rearing conditions, in which the pheromonal environment may be substantially different, can induce striking morphological changes in the perforated synapses of the AOB in adult rats.

Morphological characteristics of perforated synapses in the latter stages of synaptogenesis in rat neocortex: stereological and three-dimensional approaches.

Over recent years attention has been focused on perforated synapses (PSs), on account of their possible involvement in synaptic plasticity in the nervous system. The mechanism invoked has involved the conversion of conventional (non-perforated) synapses into perforated ones, with the latter subsequently splitting to form new daughter synapses. Data challenging this mechanism have emerged from studies using unbiased stereological and three-dimensional reconstruction procedures in early synaptogenesis and also in early- to mid-adulthood. The present study is an attempt to complement these earlier studies by concentrating on the latter part of synaptogenesis and early adulthood in rats (7-60 days postnatal). Using the disector method, the frequency of perforated synapses increases with age from 12% at seven days to 33% at 60 days. Reconstruction of the perforated synapses has led to the description of three sub-types, while quantitation of the reconstructions has highlighted major differences between perforated and non-perforated synapses over this developmental period. For instance, the postsynaptic density of perforated synapses increases in size with age, but remains static in the non-perforated variety; in addition, it is 2-3 times larger in perforated synapses. The proportion of the synaptic contact zone occupied by the postsynaptic density increases in perforated synapses with increasing age, but is static in non-perforated synapses. No evidence has been found to support a perforated synapse splitting model, since perforated synapses are present from early in synaptogenesis, the frequency of non-perforated synapses reaches a peak prior to, but not following, that of perforated synapses, and the size of the postsynaptic density of non-perforated synapses remains constant throughout the period of the study.

Immunohistochemical localization of gaba in the mammillary complex of the rat

The distribution and synaptic organization of GABAergic elements in the mammillary nuclei of rats have been examined by the immunocytochemical localization of GABA at the light and electron microscope levels. The distribution of GABA-immunoreactive fibres and terminals in the mammillary body is non-homogeneous. By light microscopy, small scattered immunoreactive terminals are observed in the pars medianus, pars posterior and ventral region of the pars medialis of the medial mammillary nucleus. Larger labelled terminals are found in the pars lateralis, the dorsal region of the pars medialis of the medial mammillary nucleus and the lateral mammillary nucleus. At the ultrastructural level, GABA-immunoreactive synaptic endings in the different subdivisions of the medial mammillary nucleus exhibit a widespread somadendritic distribution. By contrast, GABA-immunoreactive terminals within the lateral mammillary nucleus are located predominantly in the neuropil and less frequently on neuronal somata. GABA-immunoreactive synaptic endings contain pleiomorphic synaptic vesicles and have symmetrical synaptic contact zones with the somata and dendrites in the lateral and medial mammillary nuclei. After in vivo inhibition of GABA metabolism with amino-oxyacetic acid, light microscopic examination of the mammillary nuclei reveals numerous small GABA-immunoreactive cells in various subdivisions of the medial mammillary nucleus. No immunoreactive cells are observed, however, in the lateral mammillary nucleus. Electron microscopic examination demonstrates that the GABA-immunoreactive cells are astrocytes. In the labelled astrocytes, immunohistochemical reaction product is localized throughout the nucleus and cytoplasm of the cells, in thin sheet-like processes surrounding neuronal elements and in end-feet lining the basal lamina of capillaries. The results indicate that the mammillary nuclei in the rat receive a strong GABAergic innervation. Most if not all, of the GABA-immunoreactive synaptic endings in the mammillary nuclei probably arise from extrinsic inhibitory sources. The possible sources of the GABA-immunoreactive input to the mammillary complex are discussed.

Formation and maturation of synapses in primary cultures of rat cerebral cortical cells: an electron microscopic study

Cerebral cortical cells from fetal rats (18 days) were cultured for 3, 7, 14, 21, 28, 35 days in vitro (DIV) and the development of synapses was examined morphologically by electron microscopy. At 3 DIV, no synapses could be recognized. An immature type of synapse was found at 7 DIV which thereafter developed morphologically. The length of the synaptic contact zone (SCZ) increased with DIV from 271 ± 11.4 nm (mean ± SEM) at 7 DIV to 410 ± 11.4 nm at 35 DIV. The number of synaptic vesicles per terminal also increased with DIV: 10.0 ± 1.2 at 7 DIV, 35.7 ± 3.4 at 21 DIV, and 53.3 ± 4.5 at 35 DIV. The time course of numerical density of synapses was examined quantitatively by electron microscopy. Synaptic density was very low at 7 DIV. It was significantly increased at 14 DIV and thereafter showed variable changes. Four culture series showed decreases after 14 DIV, but one series showed a further increase at 21 DIV followed by a decrease at 28 DIV. The mean density of synapses at each DIV was as follows: 1780 ± 86 10 6 μ m 3 at 7 DIV, 4244 ± 595 10 6 μ m 3 at 14 DIV, 2285 ± 674 10 6 μ m 3 at 21 DIV, 2552 ± 646 10 6 μ m 3 at 28 DIV, and 2080 ± 532 10 6 μ m 3 at 35 DIV. Neuronal cell density was counted in each culture to calculate the relative number of synapses per neuron. The cell density decreased with age from 301 ± 51 10 6 μ m 3 at 7 DIV to 39 ± 9 10 6 μ m 3 at 35 DIV. The number of synapse per neuron increased with DIV to the end of the 4th week (from 64.1 ± 9.8 at 7 DIV to 1130.1 ± 254.3 at 28 DIV). The time course of synapse formation in culture resembled that in the cerebral cortex in vivo.

Effect of differential rearing on synapses and soma size in rat medial amygdaloid nucleus

The effects of differential rearing on synaptic morphology and neuronal size were examined in the medial amygdaloid nucleus (MAN) of adult rats. Forty-day-old male rats were housed in one of three ways: individually (isolated condition, IC); with four males per cage (unisexual condition, UC); or with two males and two females per cage (social condition, SC). After 2 months, the animals were prepared for electron and light microscopy. Although there was no statistically significant difference in number of synapses per unit volume in MAN, the number of perforated (P) synapses, which are characterized by discontinuities in the postsynaptic density, were significantly greater in the UC and the SC than in the IC. The length of synaptic contact zone of P synapses was also longer in both the UC and the SC compared with the IC, whereas the length of nonperforated synapses was longer only in the SC. Soma area was also larger in the SC compared with the IC. These results demonstrate that exposure to different rearing conditions, in which the pheromonal environment can be substantially different, can induce striking morphological changes in both synapses and neurons in the MAN of adult rats.

Enlargement of synaptic size as a compensative reaction in aging and dementia

A quantitative investigation has been carried out on synaptic contact zones of dentate gyrus supragranular layer and cerebellar glomeruli in autoptic samples from adult, old and demented patients. During physiological aging and senile dementia, the synaptic average area was significantly increased as compared to adult values in both the CNS areas investigated. Conversely, the number of contacts and their total surface contact area per unit volume of tissue were decreased. Current literature reports that, in animal models, enlarged synapses undergo perforations and splitting to modify synaptic connectivity. As against these assumptions, the increased synaptic size observed in our study appears to represent a compensative reaction of old and demented CNS to counteract the reduction in number and in total contact area of the synaptic junctions.

Naturally occurring degrading events in axon terminals of the dentate gyrus and stratum lucidum in the spiny mouse (Acomys cahirinus) during maturation, adulthood and aging.

The naturally occurring dynamics of presynaptic axon terminals were investigated in the dentate gyrus and stratum lucidum of the spiny mouse (Acomys cahirinus) during maturation, adulthood and aging. A sensitive and selective silver-staining technique was applied to analyze neuronal lysosome accumulation (LA), indicating synaptic degradation during development. LA was quantified by counting silver grains in the inner third and outer two thirds of the molecular layer, granular layer, and the infragranular layer of the dentate gyrus, and in the strata oriens, pyramidale, lucidum and radiatum of the medial and distal regio inferior on postnatal days 21, 28, 95, 730, and 1,460. In young and adult animals, LA was most abundant within the inner molecular layer. When animals grew older, LA densities obviously decreased in the inner molecular layer but increased in the outer molecular layer. Within the stratum lucidum only the distal regio inferior showed an extremely high LA density on postnatal day 21, dramatically decreasing thereafter and reaching adult low values during the first postnatal month. By electron microscopy in the inner molecular layer we found LA in large synaptic boutons and small terminals both with distinct synaptic contact zones. Degrading presynaptic profiles may further accumulate dense bodies, zones with completely disorganized cytoplasm, and lamellarly organized whorled membrane debris. In the distal regio inferior comparable phenomena were observed in typical mossy fiber boutons. Despite these degrading events, no electron-dense degenerating terminals were found. These results on naturally occurring nondegenerative synaptic degradation are discussed with current concepts of synaptic turnover and remodelling in the developing, adult and aging brain.

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

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

Structural plasticity of synapses in Alzheimer's disease

Plasticity of the synaptic contact zone was previously observed following loss of synapses in the cerebral cortex of normal aging humans. The present study was undertaken to determine if there was quantitative evidence of synapse loss and synapse plasticity in the inferior temporal, superior parietal, parieto-occipital, and superior frontal cortical regions in Alzheimer's disease (AD), and how such changes related to the neurofibrillary tangles and amyloid plaques. The results showed that age at autopsy did not correlate with the numbers of synapses, plaques, or tangles. However, the numbers of synapses strongly reflected the pathology of AD; in all four brain regions, there were fewer synapses as the numbers of plaques and tangles increased. In the inferior temporal and superior parietal cortices, the loss of synapses was accompanied by an increase in the synaptic contact length. The results suggest that, in some cerebral cortical brain regions, synapses are capable of plasticity changes, even when the pathology of AD and loss of synapses are severe.

Electron microscopic morphometric studies on the effects of idebenone on the synaptic remodelling activity in the hippocampus and cerebellum in normal old as well as in vitamin E-deficient adult rats

Electron microscopic morphometric investigation has been carried out on the synaptic junctions of the hippocampal dentate gyri and cerebellar glomeruli of normal, old female Wistar rats (29 months of age), and vitamin E-deficient, female adult rats (11 months of age) of the same strain. The vitamin E-deficient diet was maintained from the age of 1 month for the subsequent 10-month period. Both the normal old and the vitamin E-deficient rats were treated with a daily dose of 50 mg oxidized idebenone/kg body w/day or with its solvent (5% gum arabic) through a gastric tube during the last month before killing them. The following morphometric parameters were evaluated in the hippocampal dentate gyrus and cerebellar glomerulus: the average length of the synapses (L) the surface density (S v) and the numerical density (N v) of the synaptic contact zones. Although the idebenone treatment caused a tendency to improve these parameters in both brain compartments studied, these improvements did not reach statistical significance in the cerebellum, but did so in the case of hippocampal N v. Vitamin E deprivation caused the usual, known alterations of the synaptic parameters. Idebenone treatment during the last month of this experiment compensated the decrease of S v in both the hippocampus and the cerebellum; however, its protective effect was significant only in the case of hippocampus. Idebenone effect manifests itself in the increase of L, contributing mainly to the increase of S v, since N v remained practically invariate. Placebo treatments did not result in any significant alterations in the vitamin E-deficient group.

Morphological adaptive response of the synaptic junctional zones in the human dentate gyrus during aging and Alzheimer's disease

A computer-assisted morphometric study has been carried out on ethanol phosphotungstic acid (E-PTA) stained synaptic junctions in the human dentate gyrus supragranular layer from adult, old and Alzheimer's disease (AD)-affected patients. The number of synapses per unit volume of tissue (Nv = numerical density), the average area of the single junction (S) and the total area of the synaptic contact zones in a unit volume of tissue (Sv = surface density) were the 3 parameters taken into account. The synapse to neurone ration was also calculated for each patient. During physiological aging, Nv and Sv significantly decreased and S increased, respectively. In the AD hippocampi, Nv and Sv underwent a further decrease which was in the range of more than 40% with reference to the adult values. S was the same as the old control group. In comparison with the adult values, the number of synapse/neurone decreased by 15.6 and 48% in old and AD patients, respectively. Nv, S and Sv, while reporting on discrete ultrastructural features of the synaptic junctional zones, are closely related to each other and, taken together per group of patients, may represent a reliable index of the morphological adaptive changes taking place at the synapses. Thus, the significant increase of S both in old and AD hippocampi may be regarded as a CNS plastic response to aging and disease, although the marked decrease of Nv and Sv supports that in AD synaptic ultrastructural alterations proceed beyond a critical threshold for functional recovery.

Monocular deprivation alters the development of synaptic structure in the ectostiatum of the zebra finch

The effects of monocular deprivation, beginning at hatching, were examined in the neuropil of ectostriatum, a visual telencephalic projection area in birds. The volume of ectostriatum, the number of synapses and subsynaptic features like the presynaptic terminal size and the length of the postsynaptic contact zone were quantified in juvenile (20 d) and adult (100 d) zebra finches. Monocular deprivation affects almost all of the parameters mentioned above in juvenile birds, but only one (i.e., the size of presynaptic terminals) is permanently altered in adulthood. Both hemispheres are affected in juvenile birds with respect to the volume of ectostriatum, the length of synaptic contact zones and the presynaptic terminal size when compared to normal values. In normal birds the number of synaptic contacts is established at 20 days and remains fairly constant at 100 days. In experimental birds there is an increase in synapse number during this time period. However, no interhemispheric differences or differences compared to normal animals could be identified. The presynaptic terminals in experimental birds are smaller compared to normal values in young (25% for the deprived side; 19% for the non-deprived side) and adult (13% for the deprived side; 11% for the non-deprived side) animals. The only permanent effect caused by monocular deprivation in the ectostriatum is characterized by smaller presynaptic terminals. It is surprising that the tectofugal pathway that is believed to be mostly ipsilateral is not very vulnerable to monocular deprivation in adult animals. It is even more surprising that the deprivation effects are seen on both sides of the brain. The implications of this plasticity will be discussed in this paper.

Synaptic remodelling of perforated synapses during development and maturation in a visual projection area in birds

Perforated synapses are characterized by the appearance of one or more discontinuities in the postsynaptic density (PSD). These synapses are thought to represent intermediate stages in synaptic remodelling and turnover. To determine the dynamic level of these processes, the development of perforated synapses at different ages was examined in the neuropil of the ectostriatum, a visual projection area in birds. The overall number of perforated synapses per unit volume increases during development. Single and multiple perforated synapses, however, show a different developmental trend. Between 20 and 100 days, when the number of multiple perforated synapses decreases by 46%, single perforated synapses increase by 83% in number per unit volume. No significant changes in single or multiple perforated synapses can be observed at younger ages (i.e., 5 or 10 days). Various parameters increase between 10 and 20 days, followed by a reduction at 100 days: The relative frequency of perforations per synaptic contact, the length of the postsynaptic density including the size of the perforation, the length of the synaptic contact zone in perforated synapses excluding the size of the perforation, and the size of the perforation follow the same trend.

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.

Computer-Assisted Morphometry of Synaptic Plasticity during Aging and Dementia

A computer assisted morphometric study has been carried out on synaptic membranes in the dentate gyrus supragranular layer and cerebellar glomerulus from adult, old and demented patients. Numerical (Nv) and surface (Sv) densities as well as average area (S) of the synaptic contact zones were calculated directly on electron microscopic negatives by means of an ASBA (Wild Leitz, AG) image analyzer properly programmed. The results showed a decrease of Nv in both the CNS areas investigated during aging and, to a higher extent, in senile dementia. S was found to be significantly increased in old and demented CNS as compared with adult values. In the old hippocampus Sv was decreased by 40% whereas no significant difference was present between old and adult cerebellum; in senile dementia this parameter underwent a significant decrease in both areas investigated. We interpret the present findings in terms of morphological remodelling capability of the synaptic junctional zones during aging and disease.

The cholinergic innervation of the rat substantia nigra: a light and electron microscopic immunohistochemical study.

Putative cholinergic axons and synaptic endings were demonstrated in the substantia nigra (SN) of the rat by light and electron microscopy on the basis of the localization of choline acetyltransferase (ChAT) immunoreactivity. The distribution of ChAT immunoreactivity in the SN as demonstrated by light microscopy revealed a modest network of ChAT-immunoreactive beaded axons in the SNc, in comparison to a relatively sparse distribution in the SNr. These axonal profiles were most dense in the middle of the rostral-caudal extent of the SNc and appeared to be concentrated in the middle third of the medial-lateral extent. By electron microscopy, unmyelinated, small diameter (0.25 micron) ChAT-immuno-reactive axons were observed interspersed among numerous other non-immunoreactive axons in the SNc. ChAT-immunoreactive synaptic endings were observed in juxtaposition to small caliber (0.5 micron) non-immunoreactive dendrites, and contained numerous spheroidal synaptic vesicles and occasional mitochondria. Synaptic contact zones were characterized by an accumulation of synaptic vesicles along the presynaptic membrane, and a prominent postsynaptic densification producing an asymmetrical pre-/postsynaptic membrane profile typical of excitatory synapses. These findings provide direct evidence for a cholinergic innervation of the SN, and suggest that this input may have an excitatory effect on neuronal elements in the SNc.

Alterations in synaptic structure in the paleostriatal complex of the domestic chick, Gallus domesticus, following passive avoidance training

A morphometric study was made of synapses in both left and right hemispheres of two regions of the chick paleostriatal complex, the paleostriatum augmentatum (PA) and the lobus parolfactorius (LPO), 24 h after passive avoidance training (methyl anthranilate, M-chicks), and in water-trained controls (W-chicks). The synaptic features examined were D, the mean length of the postsynaptic thickening; Nv.syn, the numerical density of synapses; Vv.syn, the volume density of the presynaptic bouton; V, the mean volume of the presynaptic bouton; Nv.ves, the numerical density of synaptic vesicles per bouton volume; ves.syn, the number of synaptic vesicles per presynaptic bouton; and K, the curvature of the synaptic contact zone. In the LPO there is a significant increase in the numerical density of synapses (Nv.syn) in both left and right hemispheres of M-compared with W-chicks (up to 59%, depending on the method of calculation used). A hemispheric asymmetry of postsynaptic thickening length (D) which is present in W-chicks (R greater than L by 10%) is reversed in M-chicks. There is no difference in the volume density of the presynaptic bouton (Vv.syn) or the mean bouton volume (V) either between W- and M-chicks, or between left and right hemispheres. Significant changes are found after avoidance training in both of the synaptic vesicle parameters measured. There is an increase of approximately 50%, both in the numerical density of synaptic vesicles (Nv.ves) and the number of vesicles per synaptic bouton (ves.syn), in the left hemisphere of M-chicks. No changes in the mean synaptic contact curvature (K) were observed after training, either of presynaptically concave, or presynaptically convex synapses, in either left or right hemispheres, nor did the percentage distribution of these different curvature classes vary greatly. In the PA there were no significant changes in D, Nv.syn or Vv.syn, either between M- and W-chicks, or between left and right hemispheres, 24 h after passive avoidance training. However, when the differences between the mean bouton volume (V) are examined, there is a significant increase in size of the boutons in the left hemisphere of M- compared to W-chicks. There is also a hemispheric asymmetry in both Nv.ves and ves.syn in W-chicks (R greater than L by approximately 15%) and this disappears on M-training. No changes in the mean synaptic contact curvature were observed after training, either of presynaptically concave, or presynaptically convex synapses, in either left or right hemispheres. However, the percentage distribution of these different curvature classes showed some variation.(ABSTRACT TRUNCATED AT 400 WORDS)

Plasticity of the synaptic contact zone following loss of synapses in the cerebral cortex of aging humans

Quantitative ultrastructural analyses of ethanolic phosphotungstic acid-stained human layer 1 precentral mortor cortex (Brodmann's area 4) and layer 1 postcentral somatosensory cortex (Brodmann's area 3) were undertaken to determine the nature of synaptic changes occurring over a series of ages (45–84 years) of a normal aging human population. In the precentral cortex, a significant decrease in the number of synapses was accompanied by an increase in mean length of the postsynaptic contact zone and a decrease in the mean width of the presynaptic paramembranous density. The frequency of mature type A and immature type E synaptic profiles decreased with age. There were no changes in the width of the postsynaptic paramembranous density, cleft width or the number of presynaptic dense projections per synapse. In the postcentral cortex there were no significant changes in synaptic number or in any of the synaptic parameters measured. The present study demonstrates that age-related synapse loss in the human cerebral cortex may be confined to specific cortical regions. The data suggest that in the precentral cortex the plasticity of the synaptic contact zone may be a compensatory response by the remaining synapses to age-related synapse loss.