PubMed Health⌕ Search

Biomedical subjects

K E Sorra

Publications and source records attributed to K E Sorra.

7 recordsLinked to original sources

Dense core vesicles resemble active-zone transport vesicles and are diminished following synaptogenesis in mature hippocampal slices.

Large dense core vesicles (approximately 100 nm) contain neuroactive peptides and other co-transmitters. Smaller dense core vesicles (approximately 80 nm) are known to contain components of the presynaptic active zone and thought to transport and deliver these components during developmental synaptogenesis. It is not known whether excitatory axons in area CA1 contain such dense core vesicles, and whether they contribute to synaptic plasticity of mature hippocampus. Serial section electron microscopy was used to identify dense core vesicles in presynaptic axons in s. radiatum of area CA1 in adult rat hippocampus. Comparisons were made among perfusion-fixed hippocampus and hippocampal slices that undergo synaptogenesis during recovery in vitro. Dense core vesicles occurred in 26.1+/-3.6% of axonal boutons in perfusion fixed hippocampus, and in only 17.6+/-4.5% of axonal boutons in hippocampal slices (P<0.01). Most of the dense core vesicle positive boutons contained only one dense core vesicle, and no reconstructed axonal bouton had more than a total of 10 dense core vesicles in either condition. Overall the dense core vesicles had average diameters of 79+/-11 nm. These small dense core vesicles were usually located near nonsynaptic membranes and rarely occurred near the edge of a presynaptic active zone. Their size, low frequency, locations, and decrease following recuperative synaptogenesis in slices are novel findings that merit further study with respect to small dense core vesicle content and possible contributions to synapse assembly and plasticity in the mature hippocampus.

Animals↗

Overview on the structure, composition, function, development, and plasticity of hippocampal dendritic spines.

There has been an explosion of new information on the neurobiology of dendritic spines in synaptic signaling, integration, and plasticity. Novel imaging and analytical techniques have provided important new insights into dendritic spine structure and function. Results are accumulating across many disciplines, and a step toward consolidating some of this work has resulted in Dendritic Spines of the Hippocampus. Leaders in the field provide a discussion at the level of advanced under-graduates, with sufficient detail to be a contemporary resource for research scientists. Critical reviews are presented on topics ranging from spine structure, formation, and maintenance, to molecular composition, plasticity, and the role of spines in learning and memory. Dendritic Spines of the Hippocampus provides a timely discussion of our current understanding of form and function at these excitatory synapses. We asked authors to include areas of controversy in their papers so as to distinguish results that are generally agreed upon from those where multiple interpretations are possible. We thank the contributors for their insights and thoughtful discussions. In this paper we provide background on the structure, composition, function, development, plasticity, and pathology of hippocampal dendritic spines. In addition, we highlight where each of these subjects will be elaborated upon in subsequent papers of this special issue of Hippocampus.

Animals↗

Slices have more synapses than perfusion-fixed hippocampus from both young and mature rats.

Hippocampal slices have long been used to investigate properties of synaptic transmission and plasticity. Here, for the first time, synapses in slices have been compared quantitatively with synapses occurring in perfusion-fixed hippocampus, which is presumed to represent the natural in vivo state. Relative to perfusion-fixed hippocampus, a remarkable 40-50% increase in spine number occurs in adult hippocampal slices, and a 90% increase occurs in slices from postnatal day 21 rats. Serial EM shows that all of the dendritic spines have normal synapses with presynaptic and postsynaptic elements; however, not all spine types are affected uniformly. Stubby and mushroom spines increase in the adult slices, and thin, mushroom, and branched spines increase in the immature slices. More axonal boutons with multiple synapses occur in the slices, suggesting that the new synapses form on preexisting axonal boutons. The increase in spine and synapse number is evident within a couple of hours after preparing the slices. Once the initial spine induction has occurred, no further change occurs for up to 13 hr in vitro, the longest time investigated. Thus, the spine increase is occurring during a period when there is little or no synaptic activity during the first hour, and the subsequent stabilization in spine synapse numbers is occurring after synaptic activity returns in the slice. These findings suggest that spines form in response to the loss of synaptic activity when slices are removed from the rest of the brain and during the subsequent 1 hr recovery period.

Animals↗

Critical assessment of the involvement of perforations, spinules, and spine branching in hippocampal synapse formation.

Several studies propose that long-term enhancement of synaptic transmission between neurons results from the enlargement, perforation, and splitting of synapses and dendritic spines. Unbiased analyses through serial electron microscopy were used to assess the morphological basis for synapse spilitting in hippocampal area CA1. Few perforated synapses and almost no split (i.e., branched) spines occurred at postnatal day 15, an age of high synaptogenesis; thus, synapse splitting is unlikely to be important during development. The synapse splitting hypothesis predicts an intermediate stage of branched spines with both heads sharing the same presynaptic bouton. Ninety-one branched dendritic spines were traced through serial sections, and the different branches never synapsed with the same presynaptic bouton. Projections from spines, called "spinules," have been thought to extend from perforations in the postsynaptic density (PSD), thereby dividing the presynaptic bouton. Forty-six spinules were traced, and only 13% emerged from perforations in the PSD. Most spinules emerged from the edges of nonperforated PSDs, or from spine necks, where they extended into boutons that were not presynaptic to the spine. In summary, these morphological characteristics are inconsistent with synapse and spine splitting. An alternative is discussed whereby perforated synapses and spinules are transient components of synaptic activation, and branched spines appear from synapses forming in close proximity to one another.

Animals↗

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↗

Occurrence and three-dimensional structure of multiple synapses between individual radiatum axons and their target pyramidal cells in hippocampal area CA1.

Recent physiological work has used quantal analysis to investigate the properties of synaptic transmission and long-term potentiation in hippocampal area CA1. These analyses have revealed changes in the strength of excitatory post-synaptic responses following long-term potentiation that could be mediated by cellular mechanisms in the presynaptic element, in the postsynaptic element, or in both elements. In these studies, either minimal stimulation, presumably involving a single presynaptic axon, or recordings from pairs of CA3 and CA1 cells have been used. Interpretation of these quantal analyses requires knowledge about whether single or multiple synapses occur between the presynaptic axon and its target CA1 pyramidal cells. Here, light and serial electron microscopy was used to begin to examine this question and a related question concerning the ultrastructure of spines on multiple-synapse boutons. Light microscopic analyses of Golgi preparations revealed that about 20% of the axons occurring in stratum radiatum come into close apposition with two to four different dendrites of a target CA1 cell. An "apposition" was defined as a point where the axons and dendrites crossed in the same focal plane and therefore were sufficiently close to allow a dendritic spine to reach the axon and possibly establish a synaptic contact. An additional 4% of the axons wound back and forth across individual dendrites, possibly forming multiple synapses closely spaced along the dendrites. Serial electron microscopy revealed that 24% of the individual axonal boutons in stratum radiatum make synapses with multiple dendritic spines arising from either the same or different dendritic segments. Two adjacent boutons of the same axon could also be found to synapse with different spines of the same dendrite. Together with the light microscopic analysis, these observations suggest that multiple synapses occur between single axons in stratum radiatum and their target CA1 cells, and that at least some of these synapses may occur at different electronic distances. If these multiple synapses have different physiological strengths, then they may obscure or smooth peaks in the frequency histograms that are used for quantal analyses. A three-dimensional analysis was done to compare the dimensions of pairs of dendritic spines synapsing with individual axonal boutons. When the pairs of spines associated with a single bouton arose from different dendrites, at least some of which were likely to have come from different cells, the differences between their volumes and the areas of the postsynaptic densities were on average 100% and ranged up to 650%.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗