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Y Geinisman

Publications and source records attributed to Y Geinisman.

At least 19 recordsLinked to original sources

Increase in the number of axospinous synapses with segmented postsynaptic densities following hippocampal kindling.

Kindling results from intermittent electrical stimulation of a local brain region and leads to a virtually permanent augmentation of synaptic responsiveness in the stimulated circuit. It has been hypothesized that an increase in the number of synapses may represent a structural basis for the enduring expression of synaptic plasticity following kindling, but such an alteration has not been demonstrated unequivocally. The present report provides evidence that hippocampal kindling is indeed accompanied by an increase in synaptic numbers. Young adult rats were kindled via medial perforant path stimulation and sacrificed 4 weeks after reaching a criterion of 5 generalized seizures. Stimulated but not kindled and implanted but not stimulated rats served as controls. Synapses were analyzed in the middle (MML) and inner (IML) molecular layer of the hippocampal dentate gyrus. Using the stereological disector technique, unbiased estimates of the number of synapses per neuron were differentially obtained for 3 morphological subtypes of perforated axospinous synapses characterized by a fenestrated, horseshoe-shaped or segmented postsynaptic density (PSD). A significant increase in synaptic numbers was found to selectively involve only those perforated synapses which are distinguished by a segmented PSD consisting of 2-5 discrete plates. This structural modification was restricted to the terminal synaptic field of stimulated axons (MML), but was not observed in an immediately adjacent synaptic field (IML) which was not directly stimulated during kindling. Since synapses distinguished by a segmented PSD may represent specialized synaptic contacts of an unusually high efficacy, a selective increase in their numbers is likely to provide a structural substrate of the augmented synaptic gain associated with kindling.

Animals

Age-related loss of axospinous synapses formed by two afferent systems in the rat dentate gyrus as revealed by the unbiased stereological dissector technique.

Previous attempts to elucidate whether a loss of hippocampal synapses occurs during aging provided conflicting results, possibly due to the unavailability, at the time, of unbiased methods for synapse quantitation. This study was designed to reexamine the issue by means of modern technical procedures that provide unbiased estimates of synaptic numbers. Groups of 14 young adult (5 months old) and 14 aged (28 months old) male Fischer-344 rats were compared. Synapses were examined in the middle (MML) and inner (IML) molecular layer of the hippocampal dentate gyrus, where synaptic contacts are predominantly formed by different systems of afferents, the entorhinal and commissural-associational fibers, respectively. The number of synapses per neuron was estimated with the aid of the stereological dissector technique. The results showed that the total number of synaptic contacts per neuron was significantly diminished in the MML (by 23.6%) and IML (by 22.7%) of aged rats relative to young adults. This age-related synaptic loss involved axospinous, but not axodendritic, junctions of the MML (-24.4%) and IML (-24.0%). Both perforated and nonperforated axospinous synapses (distinguished by a discontinuous or continuous postsynaptic density, respectively) exhibited an age-dependent decrease in numbers, though this decrease did not reach statistical significance in the case of perforated junctions of the IML. The observed age-related loss of axospinous synapses may underlie the reduction in the amplitude of excitatory postsynaptic potentials and the decline in functional synaptic plasticity detected in the dentate gyrus of senescent rats.

Afferent Pathways

Structural synaptic plasticity associated with the induction of long-term potentiation is preserved in the dentate gyrus of aged rats.

Changes in synaptic numbers were examined in the hippocampal dentate gyrus of aged (28 months old) rats following the induction of long-term potentiation (LTP) by high-frequency stimulation of the medial perforant path carried out on each of 4 consecutive days. Potentiated animals were sacrificed 1 hour after the fourth stimulation. Stimulated but not potentiated and implanted but not stimulated rats of the same chronological age served as controls. Synapses were analyzed in the middle (MML) and inner (IML) molecular layer of the dentate gyrus. Using the stereological dissector technique, unbiased estimates of the number per neuron were obtained for the following morphological varieties of synapses: axodendritic synaptic junctions involving dendritic shafts, nonperforated axospinous synapses having a continuous postsynaptic density (PSD), and perforated ones distinguished by a fenestrated, horseshoe-shaped, or segmented PSD. The induction of LTP resulted in a selective increase in the number of synapses with segmented PSDs. This change was detected only in the potentiated synaptic field (MML), but not in an immediately adjacent one (IML), which was not directly stimulated during the induction of LTP. Comparison of these data with the results of our previous LTP study in young adult rats (Geinisman, Y. et al., 1991, Brain Res. 566:77-88) showed that the only significant difference in the absolute number of synaptic contacts per neuron between potentiated animals of the two chronological ages was an age-related reduction in segmented synapses of the MML. Relative increases in the number of segmented synapses per neuron were, however, virtually of the same magnitude in potentiated rats of both ages as compared with their respective controls. This finding may explain why senescent rats can be potentiated to the same extent as young ones.

Acoustic Stimulation

Induction of long-term potentiation is associated with an increase in the number of axospinous synapses with segmented postsynaptic densities.

Long-term potentiation (LTP) is characterized by a long-lasting enhancement of synaptic efficacy which may be due to an increase in synaptic numbers. The present study was designed to verify the validity of this suggestion using recently developed unbiased methods for synapse quantitation. LTP was elicited in young adult rats by high-frequency stimulation of the medial perforant path carried out on each of 4 consecutive days. Potentiated animals were sacrificed 1 h after the fourth stimulation. Stimulated but not potentiated and implanted but not stimulated rats served as controls. Synapses were examined in the middle (MML) and inner (IML) molecular layer of the hippocampal dentate gyrus. Using the stereological disector technique, unbiased estimates of the number of synapses per neuron were differentially obtained for the following morphological synaptic types: axodendritic synapses involving dendritic shafts, non-perforated axospinous synapses exhibiting a continuous postsynaptic density (PSD) and perforated axospinous synapses distinguished by a fenestrated, horseshoe-shaped or segmented PSD. A major finding of this study is that the induction of LTP is accompanied by a selective increase in the number of synapses with segmented PSDs. This change was detected only in the potentiated synaptic field (MML), but not in an immediately adjacent one (IML) which was not directly stimulated during the induction of LTP. It is strongly suggested by the latter finding that the increase in the number of axospinous synapses exhibiting segmented PSDs is associated with LTP. Such a highly selective modification of connectivity, which involves only one particular subtype of synapses in the potentiated synaptic field, is likely to represent a structural substrate of the enduring augmentation of synaptic efficacy typical of LTP.

Animals

The brain's record of experience: kindling-induced enlargement of the active zone in hippocampal perforated synapses.

Kindling is a consequence of intermittent electrical stimulation of a local forebrain area leading to a durable augmentation of synaptic responsiveness in the stimulated circuit. The basis for this functional change is unknown, but there is evidence suggesting that it entails a structural modification of synapses. The present report demonstrates that hippocampal kindling induces a selective enlargement of active zones in perforated axospinous synapses formed by stimulated axons. Since the active zone is the site of intracellular transmission, its enlargement involving only a certain subpopulation of synapses provides a likely structural substrate of synaptic plasticity associated with kindling.

Animals

Increase in the relative proportion of perforated axospinous synapses following hippocampal kindling is specific for the synaptic field of stimulated axons.

A comparative analysis of axospinous synapses was performed in the middle (MML) and inner (IML) molecular layer of the hippocampal dentate gyrus of rats kindled via medial perforant path stimulation and sacrificed 4 weeks after reaching a criterion of 5 generalized seizures. The MML was a directly stimulated structure, while the IML was not. Both are immediately adjacent synaptic fields likely to be equally susceptible to any generalized effects of convulsions and hypoxia. In these two subdivisions of the molecular layer, the so-called perforated and non-perforated synapses, distinguished respectively by a discontinuous or continuous postsynaptic density, were differentially quantified. In the MML, the ratio of perforated to non-perforated synapses was found to be markedly increased in kindled rats relative to controls. In the IML, however, no change in this ratio was detected following kindling. Thus, the shift in the relative preponderance of perforated synapses over non-perforated ones is not a consequence of generalized phenomena accompanying the kindling process.

Animals

Perforated synapses on double-headed dendritic spines: a possible structural substrate of synaptic plasticity.

Examination of axospinous synapses in serial sections obtained from the middle molecular layer of the rat dentate gyrus has revealed that some of them involve double-headed dendritic spines. Each spine head is apposed by a separate axon terminal with which it always forms a perforated synaptic contact distinguished by a discontinuous postsynaptic density. The number of perforated synapses on double-headed spines was estimated as a synapse-to-neuron ratio with the aid of the disector technique and found to be significantly increased in rats kindled via medial perforant path stimulation. These results support the notion that perforated synapses involving double-headed dendritic spines represent a structural modification related to enhanced synaptic efficacy.

Animals

Remodeling of synaptic architecture during hippocampal "kindling".

The "kindling" phenomenon is associated with long-lasting facilitation of synaptic transmission. A possible mechanism of such facilitation could involve changes in the number of synaptic contacts. However, previous attempts to demonstrate a synaptic morphological alteration that could account for the long-term effects of kindling had failed, possibly due to the unavailability, at the time, of unbiased methods for synapse quantitation. Using the unbiased stereological disector technique, we estimated the number of synapses per neuron in the middle molecular layer of the hippocampal dentate gyrus in rats kindled by electrical stimulation of the medial perforant path with implanted electrodes. Unkindled but stimulated (coulombic control) and unstimulated but implanted rats served as controls. Animals were coded and killed 4 weeks after reaching the kindling criterion of five generalized seizures. The most important results were obtained when axospinous synapses with continuous or discontinuous postsynaptic densities ("nonperforated" or "perforated" synapses) were differentially analyzed. Kindling resulted in a selective loss of nonperforated synaptic contacts in contrast to preservation of perforated ones. Furthermore, the ratio of perforated to nonperforated synapses was increased by 45% or 40% in kindled rats relative to unstimulated or coulombic controls, respectively. These findings suggest that synaptic efficacy may depend on a balance of the two synaptic types; selective elimination of nonperforated synapses may augment the potency of remaining synaptic contacts, a process reminiscent of synaptic remodeling during development.

Algorithms

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

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

Aging

Synapses on dendritic shafts exhibit a perforated postsynaptic density.

Synapses on dendritic shafts were examined in electron micrographs of serial sections obtained from the molecular layer of the rat dentate gyrus. Some of these synapses have been found to exhibit profiles of a discontinuous postsynaptic density (PSD). PSD reconstructions from serial sections were performed in a plane perpendicular to that of the sections. The results obtained indicate that profiles of discontinuous PSDs observed in random sections of dendritic shaft synapses are generated by sectioning of PSD plates that contain 1-3 holes or perforations. Earlier serial section studies of osmicated material have demonstrated that a proportion of axospinous synapses also exhibit a perforated PSD. It appears, therefore, that the presence of PSD perforations is a general phenomenon shared by subpopulations of different types of synapses, both those involving dendritic shafts and those involving dendritic spines.

Aging

Aged rats need a preserved complement of perforated axospinous synapses per hippocampal neuron to maintain good spatial memory.

Spatial working memory, which crucially depends on the structural integrity of the hippocampal formation and its afferent connections, is impaired in the most, but not all, of aged rats. This study was designed to verify whether aged animals that do not exhibit the spatial memory deficit are the ones in which the hippocampal synaptic connectivity remains preserved with advancing chronological age. Young adult rats with good spatial memory, aged rats with impaired spatial memory and equally aged rats with intact spatial memory were compared. The number of synapses per neuron was estimated in the hippocampal dentate gyrus. The most important results were obtained when axospinous synapses were divided into perforated and non-perforated ones according to the appearance of their postsynaptic density. A significant decrease in the number of perforated synapses was found in memory-impaired aged rats as compared to either young adults or aged animals without memory deficits. The number of non-perforated synapses per neuron was diminished in memory-deficient aged rats relative to young adults, but not to memory-intact aged rats. However, it was only the loss of perforated synapses which correlated with the degree of spatial memory impairment. Thus, aged rats need a preserved complement of hippocampal perforated synapses to maintain good spatial memory.

Aging

Loss of perforated synapses in the dentate gyrus: morphological substrate of memory deficit in aged rats.

Most, but not all, aged rats exhibit a profound deficit in spatial memory when tested in a radial maze--a task known to depend on the integrity of the hippocampal formation. In this study, animals were divided into three groups based on their spatial memory capacity: young adult rats with good memory, aged rats with impaired memory, and aged rats with good memory. Memory-impaired aged animals showed a loss of perforated axospinous synapses in the dentate gyrus of the hippocampal formation in comparison with either young adults or aged rats with good memory. This finding suggests that the loss of perforated axospinous synapses in the hippocampal formation underlies the age-related deficit in spatial memory.

Aging

Loss of axosomatic synapses in the dentate gyrus of aged rats.

Axosomatic synapses involving granule cells of the dentate gyrus were studied by means of quantitative electron microscopic analysis in young adult (3-month-old) and aged (25-month-old) rats. The number of axosomatic synapses per unit length of neuronal soma membrane was found to be significantly lower (by 15%) in aged animals than in young adults. This decrease in synaptic numbers is not associated with age-related changes in the size of neuronal soma profiles or in the length of their plasma membranes. The ratio between the total length of synaptic appositions and the membrane length of a neuronal soma profile was diminished by 22% in aged rats, whereas the mean length of synaptic apposition was 10% less in these animals than in young adults. These data, taken together, suggest that an absolute loss of axosomatic synapses occurs with advanced age. It appears, therefore, than not only the loss of axodendritic synapses, described previously, but also the loss of axosomatic synapses, found here, contributes to the process of age-related partial deafferentation of neurons in the rat dentate gyrus.

Afferent Pathways

Interganglionic axonal transport of neural peptides within the nervous system of Aplysia.

Neurons of the circumesophageal ganglia of Aplysia synthesize 1--2000 dalton peptides and subject them to axonal transport in large quantities in the pleuro-visceral connective and pedal nerves. Most of the protein transported in the connective nerves accumulates in the abdominal ganglion, although some passes out its peripheral nerves. Autoradiography revealed no evidence for terminations of the transporting axons in possible neurohemal areas of this ganglion. It is suggested that these data reflect the existence of a pathway mediating the "directed delivery" of neural peptides in this nervous system.

Animals

Dendritic atrophy in the dentate gyrus of the senescent rat.

Quantitative electron microscopic analysis of the supragranular zone of the dentate gyrus molecular layer has shown that the number, volume fraction and surface area of dendritic shaft profiles are significantly decreased in senescent rats, relative to young adults. These modifications of dendritic morphology, which are not associated with age-related changes in dimensions of the molecular layer or in numbers of granule cells, may result from a decrease in the number and/or length of dendrites. In either case, the decreases in the number, volume fraction and surface area of dendritic shaft profiles found in the dentate gyrus of senescent rats signify an age-related atrophy of dendrites. Comparison of changes in the number and volume fraction of dendritic shaft profiles has demonstrated that age-related dendritic atrophy involves predominantly dendritic branches.

Aging

Hypertrophy of astroglial processes in the dentate gyrus of the senescent rat.

Quantitative electron microscopic analysis of the supragranular zone of the dentate gyrus molecular layer has shown that the number and volume fraction of profiles of astroglial processes are significantly increased in senescent rat relative to young adults. These ultrastructural modifications, which are not associated with significant age-related changes in the number of astrocytes or in the width of the molecular layer, may result from a formation of new astroglial processes and/or elongation of existing ones. In either case, the increase in the number and volume fraction of astroglial process profiles is an indicator of age-related astroglial hypertrophy. Hypertrophy of astroglial procecesses, which seems to develop with advanced age as a response to partial deafferentation of neurons, may compensate for a decrease in the dendritic volume fraction, thereby preventing changes in the dimensions of the dentate gyrus molecular layer in senescence.

Aging