Biomedical subjects

O Steward

Publications and source records attributed to O Steward.

At least 91 records · Page 5Linked to original sources

PubMed1990

Differential subcellular localization of particular mRNAs in hippocampal neurons in culture.

In situ hybridization was used to assess the subcellular distribution of mRNAs encoding several important neuronal proteins in hippocampal neurons in culture. mRNA encoding GAP-43, a protein that is largely excluded from dendrites, was restricted to nerve cell bodies, as were mRNAs encoding neurofilament-68 and beta-tubulin, which are prominent constituents of dendrites and of axons. In contrast, mRNA encoding MAP-2, a protein that is selectively distributed in dendrites and cell bodies, was present in both dendrites and cell bodies. These results demonstrate that different mRNAs are differentially distributed within individual hippocampal neurons. Taken together with previous findings from other laboratories, our results suggest that only a limited set of mRNAs are available for local translation within dendrites.

Animals↗

PubMed1990

Spatial overlap between populations of synapses determines the extent of their associative interaction during the induction of long-term potentiation and depression.

1. This study evaluates the associative interactions between inputs that lead to long-term potentiation (LTP) and long-term depression (LTD) in the dentate gyrus (DG). Previous studies have revealed that when two inputs are coconditioned, the extent of LTP is greater than when each input is conditioned alone. Moreover, for a weak input that does not show LTP when conditioned alone, LTP can be induced in that weak input if it is coconditioned with a strong input. LTD results when one input is silent when another is conditioned. In the present study, we evaluate whether these associative interactions depend on the extent of overlap of the terminal fields of the different inputs. 2. The experiment took advantage of the topographical organization of the temporodentate pathway from the entorhinal cortex (EC) to the DG. Four stimulating electrodes were placed so as to activate ipsilateral and crossed components of the projections from medial and lateral portions of the EC. Recording electrodes were positioned unilaterally in the DG so as to record field potentials. The localization of the synaptic field that was activated by each electrode was determined by current source density (CSD) analysis. The extent of overlap between the terminal fields of ipsi- and contralateral pathways was assessed, and the pathways were divided into groups where the overlap between current sinks was 0-50 or 51-100%. 3. Conditioning stimulation (400-Hz trains of 8 pulses delivered 8 times) was delivered to pathways alone or in combination with other pathways. The extent of LTP was evaluated after coactivation of pathways that overlapped substantially (51-100%) or minimally (0-50%). The extent of LTD was evaluated in pathways that were silent during conditioning of other overlapping or nonoverlapping pathways. 4. The extent of associative LTP or LTD depended on the extent of overlap between the terminal fields of pathways. Coactivation of two pathways that overlapped by 51-100% led to LTP; coactivation of pathways that overlapped by 0-50% did not. Moreover, LTD was induced in a crossed pathway when an ipsilateral pathway that overlapped by 51-100% was activated, but not when a nonoverlapping (0-50% overlap) ipsilateral pathway was activated. The degree of associative LTP or LTD that was induced in crossed pathways was correlated with the percent overlap with the terminal field of the active ipsilateral pathway. 5. Evaluation of whether LTD was induced when one division (medial or lateral) of the ipsilateral pathway was silent when the other division was conditioned revealed similar relationships.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1990

Dendritic transport: quantitative analysis of the time course of somatodendritic transport of recently synthesized RNA.

We have previously reported that recently synthesized RNA is selectively transported into the dendrites of hippocampal neurons grown in culture (Davis et al., 1987). The present study provides further details about this transport process, focusing especially on the velocity of transport, by comparing the velocity of dendritic transport of RNA in neurons of different ages and in the branched and unbranched dendrites of individual neurons. In our previous study, we recognized that calculations of transport velocity could be compromised because transport was being evaluated in a population of dendrites of varying lengths. The present study uses a mathematical modeling approach to determine how the morphology of the population of dendrites would affect the analysis of transport velocity. Focusing first on a simple model, we compared the distribution of transported material at various times when all dendrites were of the same length and when the population included dendrites of different lengths. We found that the distance of labeling increased linearly over time when all dendrites were of the same length, but increased with a negatively accelerating curve when dendrites were of different lengths. We then determined the actual distribution of dendritic lengths in cultured hippocampal neurons, based on immunostaining with an antibody directed against the selective dendritic marker, microtubule-associated protein 2 (MAP2). Using a computer model, we calculated the mean distance of transport as a function of time in this population of dendrites, assuming different velocities of transport. The velocity that best fit the measured distances of RNA transport in both 7- and 15-d-old neurons was 11 microns/hr (0.26 mm/d). However, for the dendrites exhibiting the longest distance of labeling, the best-fitting curve assumed a velocity of 21 microns/hr in both 7- and 15-d-old neurons (0.50 mm/d). Comparisons of transport in branched and unbranched dendrites revealed that the distance of labeling over branched dendrites was consistently longer than over unbranched dendrites of individual neurons. However, neurons with a larger proportion of branched dendrites did not exhibit a greater mean distance of transport. The density of silver grains was higher over branched than over unbranched dendrites, suggesting that a greater amount of recently synthesized RNA may be transported into branched dendrites. Taken together, these results suggest that RNA transport into dendrites is regulated differentially in the dendrites of individual neurons.

Animals↗

PubMed1990

The process of reinnervation in the dentate gyrus of adult rats: time course of increases in mRNA for glial fibrillary acidic protein.

The present study evaluates the time course of increased expression of the mRNA for glial fibrillary acidic protein (GFAP) within the dentate gyrus and hippocampus after unilateral lesions of the entorhinal cortex. Levels of GFAP mRNA were evaluated by dot blot hybridization of mRNA isolated from the hippocampus and quantitative in situ hybridization. For dot blot hybridization, RNA was isolated from pooled hippocampi obtained from animals killed at 12 hr, 1, 2, 4, 6, 8, 10, 14, and 30 d postlesion. A separate set of animals killed at 2, 4, 6, 8, 10, 12, 14, and 32 d were prepared for in situ hybridization. The dot blot analyses of mRNA isolated from the hippocampus revealed that on the side ipsilateral to the lesion, the levels of GFAP mRNA increased rapidly, reaching a peak at 2 d postlesion. The increases were not evident by 12 hr postlesion, but by 24 hr, levels of GFAP mRNA were 5-fold higher than control, and by 48 hr, the levels were over 6-fold higher than control. The levels of GFAP mRNA decreased after 2 d postlesion. At 4 and 6 d postlesion the levels were about 2-fold higher than control. At later postlesion intervals, mRNA levels were comparable to the control. At 2 d postlesion, the levels of GFAP mRNA were also increased about 2-fold over control levels on the contralateral side. After 2 d, the levels of GFAP mRNA on the contralateral side were comparable to the control. In situ hybridization revealed a complex pattern of changes in the levels of GFAP. At 2 d postlesion, the levels of GFAP mRNA increased dramatically throughout the hippocampus bilaterally. The increases were most pronounced in the denervated portions of the neuropil; however, the levels of GFAP mRNA were also substantially elevated in laminae that do not receive direct projections from the entorhinal cortex. GFAP mRNA levels were also increased in other areas that receive projections from the entorhinal cortex, including the septum, lateral-dorsal thalamus, and entorhinal cortex contralateral to the lesion. In addition, GFAP mRNA levels were increased in regions bordering the ventricles throughout the brain, and over the surface of the tectum. After 2 d postlesion, the increases in the levels of GFAP mRNA were for the most part restricted to areas containing terminal degeneration. The generalized increases throughout the hippocampus were no longer apparent. Areas bordering the ventricles continued to exhibit higher labeling than in control animals, but this effect was not as prominent as at 2 d postlesion.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1989

Decreases in excitatory synaptic transmission and increases in recurrent inhibition in the rat dentate gyrus after transient cerebral ischemia.

Excitatory transmission along the perforant path from the entorhinal cortex to the granule cells of the dentate gyrus was evaluated two days after 10 min of transient cerebral ischemia in the rat. The amplitude of the population spike, and the amplitude and the initial slope of the population excitatory postsynaptic potential (EPSP) evoked by the perforant path stimulation were measured across a range of stimulus intensities, and were compared with control values. Inhibitory interactions were evaluated using the paradigm of paired pulse stimulation, comparing the amplitude of the population spike evoked by the second pulse of a pair to the initial spike. The maximal values of the initial slope of the population EPSP and the population spike were reduced in the ischemic group. Also, the extent of paired pulse inhibition was greater in the ischemic group. These results suggest that: (1) excitatory synaptic transmission along the perforant path is impaired in the postischemic period, (2) inhibition of the dentate granule cells is enhanced in this period. These results are not consistent with the hypothesis that there is a hyperactivation of the tri-synaptic circuit in the chronic postischemic period that accounts for the excitotoxic death of CA1 neurons.

Action Potentials↗

PubMed1989

Comparison of the neurotoxic effects of colchicine, the vinca alkaloids, and other microtubule poisons.

Previous studies have revealed that colchicine is selectively toxic to certain neuronal populations in the CNS, particularly granule cells of the dentate gyrus. The present study evaluates whether other microtubule poisons exhibit similar neurotoxic effects. Equimolar solutions of colchicine, colcemid, podophyllotoxin, vinblastine, vincristine and lumicolchine, the non-binding analog of colchicine, were injected into the dentate gyrus. Neurotoxicity was evaluated histologically. As previously reported, colchicine selectively destroyed dentate granule cells with minimal damage to other neurons including hippocampal pyramidal cells. Vincristine was very toxic and was not selective for granule cells. Vinblastine was relatively selective in destroying granule cells, but was not as potent as colchine. Colcemid and podophyllotoxin had minimal toxic effects. Lumicolchine injections caused no more damage than injections of vehicle. This ordering appears to correlate with the reversibility of binding tubulin.

Animals↗

PubMed1989

Reorganization of neuronal connections following CNS trauma: principles and experimental paradigms.

The present review summarizes how the nervous system responds to trauma. The goal is to provide an introduction to the problems, techniques, experimental paradigms, current issues, and future promise. The review is especially designed for basic scientists and clinicians who are not currently involved in research on CNS reorganization, and for students just entering the field. The review characterizes the secondary degenerative events that occur after trauma, and the types of growth that commonly occur. A standard terminology is set forth with criteria for differentiating between related phenomena. Experimental methods are described that can be used documenting reorganization of circuitry. The principles that determine whether a given process will or will not occur are summarized, and some of the factors that may regulate the nature and extent of growth are considered. Research strategies are outlined that have been used to evaluate whether reorganization of circuitry is functionally significant. Finally, future directions in research and clinical application are discussed, focusing especially on the efforts to facilitate regeneration, and the work on transplants of CNS tissue to facilitate growth of surviving connections, and to replace tissue destroyed by trauma.

Animals↗

PubMed1989

Synaptic reorganization within the human central nervous system following injury.

Behavioral recovery following brain injury in humans is well recognized; however, the anatomical basis for such recovery has not been demonstrated. Two cases are presented that show reorganization of synaptic connections (plasticity) in the dentate gyrus of human brain following uncal herniation. The neurohistological appearance of these cases is very similar to a well-described animal model of anatomical, physiological, and behavioral recovery following experimental surgical injury.

Acetylcholinesterase↗

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↗

PubMed1988

The process of reinnervation in the dentate gyrus of adult rats: an ultrastructural study of changes in presynaptic terminals as a result of sprouting.

The present study was undertaken to define the ultrastructure of synapses of the crossed temporodentate pathway after they had sprouted to reinnervate the dentate gyrus following the destruction of the normal ipsilateral temporodentate pathway. The synapses of the sprouted crossed temporodentate pathway were identified at the EM level by using autoradiographic techniques and by evaluating the degeneration of the pathway following secondary lesions. Both EM autoradiography and EM degeneration revealed that the terminals of the sprouted crossed temporodentate pathway formed asymmetric synapses on spines; individual terminals appeared to make more synaptic contacts per terminal (multiple synapses) than in the case of the normal crossed pathway. In the two lesioned animals exhibiting the best labeling, labeled terminals made an average of 3.0 +/- 2.2 and 2.0 +/- 1.3 contacts per terminal. In contrast, labeled terminals in normal animals exhibited only one contact per terminal. The terminals of the sprouted pathway were also larger than those of the normal crossed pathway. The synapses of the crossed temporodentate pathway that degenerated after a secondary lesion of the entorhinal cortex exhibited both electron-lucent and electron-dense forms of degeneration at 2 days postlesion. In two animals that were quantitatively analyzed, the density of degenerating synaptic terminals was 281 and 218/10,000 microns2 in the terminal field of the sprouted crossed pathway. These values are much higher than in normal animals, where the density of degenerating synaptic terminals was only 2.12/10,000 microns2 at 2 days postlesion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Protein synthesis by rat hippocampal slices maintained in vitro.

The present study evaluates protein synthesis in rat hippocampal slices maintained in vitro. Transverse slices of hippocampus were prepared from both adult rats and rat pups during postnatal development and incubated in a gassed (95% O2/5% CO2) balanced salt medium containing 5 nM 3H-leucine. The time course of 3H-leucine incorporation into TCA-precipitable protein was determined using slices removed from the media after 5, 10, 20, 30, 40, 60, and 120 min of incubation. The pattern of 3H-amino acid incorporation was evaluated by fixing slices with paraformaldehyde, embedding the slices in plastic, and sectioning the slices end on and en face for autoradiographic analysis. Biochemical analysis of 300 and 400 micron slices revealed that incorporation of leucine into protein proceeds at a constant rate. The autoradiographic analysis revealed that in adult hippocampal slices of 300-600 micron thickness there was complete penetration of 3H-leucine with no indication of a gradient in the extent of incorporation throughout the slice. The pattern of grain density within 300-600 micron slices matches that previously reported after in vivo injections of radiolabeled amino acid, where grain density is highest over neuronal cell bodies and lower over the laminae that contain dendritic processes and axons (Phillips et al: Mol Brain Res 2:251-261, 1987). Hippocampal slices of 200, 800, and 1,000 micron thickness showed irregular labeling. Slices of 200 micron were filled with pyknotic nuclei and vacuoles and exhibited patchy labeling. In 800 micron slices there were isolated areas of good preservation within the slice core, but these areas exhibited little incorporation. Relative to the 300-600 micron slices, there was a higher number of pyknotic nuclei and a much deeper layer of necrosis along the cut edges. Slices of 1,000 micron thickness showed poor preservation throughout and low levels of incorporation. Biochemical studies revealed a much higher rate of incorporation in the slices prepared from postnatal animals. Autoradiography of the slices from developing rats revealed that penetration was excellent and incorporation appeared to be greater as judged by an overall higher grain density. We believe that rat hippocampal slices provide a good in vitro model of protein metabolism that will be useful for studies of protein synthesis in isolated cell body and dendritic laminae and for the evaluation of whether protein synthesis in particular laminae is regulated by synaptic activity.

Amino Acids↗

PubMed1988

Protein synthesis and processing in cytoplasmic microdomains beneath postsynaptic sites on CNS neurons. A mechanism for establishing and maintaining a mosaic postsynaptic receptive surface.

Recent studies have shown that protein synthetic machinery consisting of polyribosomes and associated membranous cisterns is selectively localized beneath synaptic sites on neurons. In the present paper, the role of this machinery in neuronal function will be considered. We will: 1. Summarize the studies that characterize the polyribosomes and define their associations with membranous cisterns. Taken together, these observations suggest the existence of a system for the synthesis and posttranslational processing of proteins at individual synaptic sites; 2. Review the evidence that the protein synthetic machinery is particularly prominent during the initial formation of synaptic contacts (during early development), and during lesion-induced synaptogenesis in mature animals. These observations have led to the hypothesis that the polyribosomes produce proteins that play a role in the formation of the synaptic junction; 3. Review evidence that supports the hypothesis that there is a local synthesis of protein within dendrites, as well as local glycosylation; 4. Describe the evidence suggesting that at least some of the protein constituents of the synaptic junction itself are synthesized locally; and 5. Describe our studies that reveal a mechanism for selective dendritic transport of RNA; this transport mechanism permits the delivery of RNA to postsynaptic sites throughout the dendritic arbor. We will advance the hypothesis that neurons position protein synthetic machinery together with the mRNA's that are appropriate for particular synapses beneath synaptic contact regions. At the synaptic site, this machinery could then direct the synthesis of particular proteins that are critical for synapse formation or maintenance. The positioning of protein synthetic machinery at postsynaptic sites permits a rapid local regulation of the production of key proteins by events at individual synapses.

Animals↗

PubMed1988

Changes in the firing properties of neurons in the dentate gyrus with denervation and reinnervation: implications for behavioral recovery.

The present study evaluates how the activity of neurons in the dentate gyrus of adult rats is affected by removal of the projection from the ipsilateral entorhinal cortex (EC) and by the reinnervation which follows this injury. We evaluated the average firing rate and characterized interstimulus interval (ISI) parameters for single units in the granule cell layer of the dentate gyrus in two ways: (I) by recording the activity of single neurons prior to and at 15 min and 2, 4, 6, and 8 h. following a unilateral EC lesion; and (II) by calculating average rates for samples of neurons at 2, 4, 6, 8, and 14 days postlesion. Of a sample of 31 neurons whose activity was recorded before and after an EC lesion, 27 (87%) showed decreased activity, and 4 (13%) showed increased activity. The average prelesion firing rate for all cells was 6.5 spikes/s, and the average rate decreased to 2.5 spikes/s at 15 min postlesion. The average firing rate remained depressed for the 8-h recording session, although it was not possible to maintain the recordings for all cells. Evaluations of ISI histograms revealed three general types: (a) a skewed distribution with a single peak; (b) a bimodal distribution with an early peak at intervals of a few ms and a later peak at approximately the same interval as the distributions with single peaks; (c) cells with low firing rates and more or less rectangular distributions. Cells producing each type of ISI histogram exhibited decreases in firing after EC lesions. However, the 4 neurons that exhibited increases in firing had relatively low firing rates prior to the lesion. There were no significant changes in the coefficient of variation or skewness of the ISI histograms following the lesions. The statistical dependency of successive ISIs as revealed by serial correlograms was relatively low in the prelesion sample, and showed no consistent change following the lesion. Comparison of the average firing rates of different samples of neurons at 2-14 days postlesion revealed that the average activity of neurons in the granule cell layer remained depressed at 2 and 4 days postlesion. However, the activity recovered to a level comparable to the prelesion control by 8 days postlesion. The time course of recovery of unit activity was comparable to the time course of sprouting as revealed by previous electrophysiological studies.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1988

An immunocytochemical and biochemical study of the microtubule-associated protein MAP-2 during post-lesion dendritic remodeling in the central nervous system of adult rats.

A monoclonal antibody against the microtubule-associated protein MAP-2 was used to examine the fate of this molecule during post-lesion dendritic remodeling in the hippocampus and septum of adult rats. Qualitative and quantitative immunocytochemical analyses were carried out in the dentate gyrus after unilateral destruction of the entorhinal cortex (EC). An increase in MAP-2 immunoreactivity was detected in dendritic processes located in the outer 2/3 of the ipsilateral molecular layer (ML) 2 days after the lesion. whereas dendritic staining decreased considerably in the inner 1/3 of the same ML. The increase of staining was also detected 4, 6 and 8 days after the lesion; it was accompanied by an increase in the immunoreactivity in the inner 1/3 of the ML. After that period, a progressive decrease in anti-MAP-2 staining toward control levels was detected along the whole extent of the ipsilateral ML. This was concurrent with alterations in dendritic orientation, and a decrease in stained dendrites in the inner 1/3 of the ML. By 30 days post-lesion anti-MAP-2 staining was almost identical to that of the contralateral ML, although the alterations in dendritic morphology were still present in the ipsilateral ML. Changes in MAP-2 levels were also evaluated by densitometry of Western blots or dot immunobinding of hippocampal extracts obtained at different post-lesion intervals. The results obtained revealed a pattern of change in MAP-2 levels identical to that observed with the immunohistochemical stain. A similar, immunocytochemical and biochemical, analysis conducted in the lateral septal nucleus after unilateral transection of the fimbria showed no changes in the distribution and/or content of MAP-2 at any post-lesion interval analyzed (2, 10 and 20 days post-lesion). The present observations show that post-lesion dendritic remodeling is concurrent with modifications in the levels and distribution of MAP-2. These modifications suggest that the dendritic cytoskeleton is dynamically changing in response to perturbation of the synaptic environment. In addition, our results indicate that these changes may only occur in those neurons which have the capability to remodel their post-synaptic surface in response to deafferentation.

Animals↗

PubMed1988

Evidence that associative interactions between synapses during the induction of long-term potentiation occur within local dendritic domains.

The present study evaluates whether the associative interactions between synapses that lead to long-term potentiation and depression (LTP and LTD) can occur between spatially segregated synapses of the medial and lateral temporodentate pathway of the rat. Coconditioning of crossed and ipsilateral pathways resulted in LTP of the crossed system only when the current sinks of the two conditioned pathways overlapped sufficiently. Likewise, conditioning of an ipsilateral pathway alone resulted in LTD of the crossed pathway only when those current sinks overlapped sufficiently. These observations support the idea that associative events that lead to LTP or LTD can be restricted to a local dendritic domain. The postsynaptic cell can therefore serve as more than one unit of integration for synaptic modification.

Animals↗

PubMed1988

Protein-synthetic machinery beneath postsynaptic sites on CNS neurons: association between polyribosomes and other organelles at the synaptic site.

Previous studies have demonstrated that polyribosomes are selectively positioned beneath postsynaptic sites on CNS neurons. In spine-bearing neurons, these polyribosomes are selectively localized at the base of the spines, and occasionally within spine heads. The present study evaluates whether there are relationships between the polyribosomes and other organelles of the postsynaptic cytoplasm, including membranous cisterns and spine apparatuses. Dendritic spines from the dentate gyrus and hippocampus of the rat were analyzed at the electron-microscopic level in 2 ways. First, relatively thick sections were prepared for electron microscopy, and spines were photographed in stereo using a goniometer stage. Second, conventional serial thin sections were taken, and spines were reconstructed. From the stereo photographs and serial reconstructions, we determined the proportion of polyribosomes that was associated with membranous cisterns. We also counted the number of ribosomes per cluster to determine whether there were differences between polyribosomes in different intradendritic locations, or between free polyribosomes and polyribosomes on cisternal membranes. From the serially reconstructed spines we determined the incidence of polyribosomes, membranous cisterns, and spine apparatuses, and evaluated the relationships between these organelles. We found that in both the dentate gyrus and hippocampus, about 50% of the polyribosomes that were present beneath the base of spines were associated with membranous cisterns. Polyribosomes that were present in the head of the spine were rarely associated with a cistern, however. The overall incidence of polyribosomes was similar in spines with spine apparatuses and spines without a spine apparatus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Facilitation of kindling by prior induction of long-term potentiation in the perforant path.

Previous studies have revealed that a form of synaptic potentiation resembling long-term potentiation (LTP) occurs at various sites as a result of stimulation that leads to kindling. The present study evaluates what role this synaptic potentiation plays in the development of kindling following periodic stimulation of the entorhinal cortex of the rat. LTP was repetitively induced in the pathway from the entorhinal cortex (EC) to the dentate gyrus (DG) by daily stimulation with high frequency trains that led to LTP, but did not evoke afterdischarge (AD). Subsequently, animals received stimulation designed to induce kindling (that led to AD), and this stimulation was delivered once per day until kindled seizures were induced. While repetitive induction of LTP was not sufficient to produce kindling, prior induction of LTP significantly increased the rate of subsequent kindling as evidenced by a decrease in the number of kindling stimulations required to induce the kindled state. As a group, animals that had received stimulation designed to induce LTP developed kindled seizures after an average of 10 AD's, whereas a control group that had received non-potentiating stimulation required 25 AD's. These results indicate that LTP at EC-DG synapses cannot represent the mechanism of kindling following EC stimulation. However, synaptic potentiation at this site can facilitate the development of epileptogenesis in response to subsequent activation of the perforant path.

Action Potentials↗

PubMed1987

An immunocytochemical and biochemical study of the microtubule-associated protein Tau during post-lesion afferent reorganization in the hippocampus of adult rats.

A monoclonal antibody against the microtubule-associated protein (MAP) Tau was used to examine the fate of this molecule during post-lesion afferent reorganization in the hippocampus of adult rats. An immunocytochemical analysis was carried out in the dentate gyrus after unilateral destruction of the entorhinal cortex (EC). In the non-denervated hippocampus, Tau immunoreactivity was detected in parallel axons and mossy fibers; no staining was present in neuronal cell bodies and dendrites. A significant decrease in Tau immunoreactivity was detected in the outer 2/3 of the ipsilateral dentate gyrus molecular layer (ML) 2 days after an EC lesion, whereas staining in the inner 1/3 of the same ML increased considerably. This was followed by a very rapid recovery of Tau immunoreactivity in the outer 2/3 of the denervated ML, which by 10 days post-lesion was almost identical to that of the contralateral non-denervated ML. A similar phenomenon was observed in other regions of the hippocampus denervated by the EC lesion. The modifications in Tau immunoreactivity in the denervated hippocampus were also accompanied by changes in the polypeptide composition of this heterogeneous group of MAPs, as revealed by immunoblot analysis of hippocampal extracts obtained at different post-lesion intervals; these changes involved a rapid and significant increase in low molecular weight migrating Tau-immunoreactive polypeptides. The present observations indicate that important modifications in Tau proteins occur in the deafferented hippocampus, a phenomenon that may well be related with the regulation of microtubule polymerization during post-lesion axonal growth.

Animals↗