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O Steward

Publications and source records attributed to O Steward.

At least 145 records · Page 8Linked to original sources
PubMed1980

Preferential neurotoxicity of colchicine for granule cells of the dentate gyrus of the adult rat.

Injections of 5-7 microgram (6-9 nmol) of colchicine into the dentate gyrus of the hippocampus of mature rats result in widespread destruction of dentate granule cells with little, if any, damage to other cell populations, including hippocampal pyramidal cells. Selective destruction of dentate granule cells is also observed after intraventricular injections. The destructive effects of colchicine appear as soon as 12 hr after the injection and lead to the disappearance of the granule cells over a period of days. Whereas the effects on nongranule cell populations in the hippocampus appear to be reversed by approximately 11 days after injection, the granule cells are almost completely absent at long intervals after injection. At the long postinjection survival intervals the disappearance of the granule cells is accompanied by elimination of their terminal projections, the mossy fibers, as revealed by Timm staining for heavy metals. Because the preferential neurotoxic effects of colchicine do not result in morbidity or obvious behavioral debilitation, the toxicity may prove useful for studying the functional consequences of removing specific cell populations in the central nervous system.

Animals↗
PubMed1979

Functional effects of lesion-induced plasticity: long term potentiation in formal and lesion-induced temporodentate connections.

The crossed temporodentate pathway from the entorhinal cortex of one hemisphere which proliferates in response to a contralateral entorhinal lesion in adult rats was analyzed for its ability to exhibit long term potentiation of synaptic efficacy similar to that which occurs in the normal ipsilateral temporodentate pathway. It was found that while the small synaptic response evoked by contralateral entorhinal cortical stimulation in normal rats does not undergo long term potentiation, after unilateral entorhinal lesions and proliferation of the crossed temporodentate pathway, the crossed pathway acquires a capacity for potentiation of synaptic action which qualitatively resembles that of the normal ipsilateral temporodentate circuit. However, despite the potentiation of synaptic drive, no long term enhancement of cell discharge was observed in the re-innervated dentate gyrus even through potentiation of this parameter was very prominent in the ipsilateral pathway. Mechanisms are discussed by which a previously non-potentiating pathway may acquire, as a consequence of lesion-induced sprouting, an ability to undergo long term potentiation of synaptic efficacy in a fasion similar to the ablated pathway. Reasons for the failure to observe potentiation of cell firing are also considered.

Acetylcholinesterase↗
PubMed1979

Synapses as associative memory elements in the hippocampal formation.

This report analyzes long term potentiation (LTP) and associative interactions between synapses of the ipsilateral and crossed entorhinal cortical (EC) pathways to the dentate gyrus (DG). In the anesthetized rat, conditioning stimulation to one EC-DG pathway reliably elicits LTP at the ipsilateral synapses, while the synapses of the collateral, crossed pathway to the contralateral DG do not exhibit LTP. Furthermore, in the DG ipsilateral to the conditioning stimulation the convergent crossed pathway from the contralateral side, which had not been itself conditioned, failed to exhibit heterosynaptic LTP. These results are consistent with a specific 'synaptic' localization of the changes responsible for LTP, and suggest that some critical number of synapses must be activated in order to observe LTP. While the crossed EC-DG projection never exhibited LTP when conditioned alone, the crossed input could be potentiated under certain circumstances. Specifically, paired conditioning of ipsi- and contralateral inputs by nearly simultaneous conditioning stimulation of the EC bilaterally results in LTP in the crossed system. Furthermore, this associatively induced LTP of the crossed system can be reversed by subsequent conditioning of the ipsilateral system alone. Successive potentiating and depotentiating sequences are possible using paired and non-paired stimulation procedures even after lesions which prevent neural loops through the EC. The results are interpreted as evidence for a 'Hebb' type synapse which has the capability for erasure. This synaptic type is not appropriate for classical conditioning without appendant circuitry, but is suited for other forms of associative learning.

Animals↗
PubMed1979

Analysis of the habituation-like changes in transmission in the temporodentate pathway of the rat.

Habituation-like decrements in extracellular measures of synaptic activation (population EPSP) and cell discharge (population spike) were analyzed in the dentate gyrus of the rat following repetitive low-frequency stimulation of the medial and lateral entorhinal cortex. Stimulation of either subdivision of the entorhinal projection system resulted in comparable habituation-like response decrements with similar stimulation regimens. However, habituating stimulation of one subdivision did not result in decreased responsiveness to stimulation of the other. Repetitive low-frequency stimulation or even a single pulse delivered to either subdivision did, however, result in a potentiation of granule cell discharge in response to stimulation of the other subdivision (a form of heterosynaptic potentiation). This heterosynaptic potentiation of granule cell discharge was not accompanied by any increase in the extracellular EPSP. Comparisons of the relationship between the population EPSP and population spike before and during habituating stimulation revealed changes in cell discharge in response to the habituating stimulus which could not be accounted for by changes in synaptic activation alone. The results suggest that repetitive activation of the temporodentate pathway alters granule cell output as a result of two processes, a habituation-like decrement in synaptic activation, and a potentiation of granule cell discharge as a consequence of prior activation.

Afferent Pathways↗
PubMed1978

Polysynaptic activation of the dentate gyrus of the hippocampal formation: an olfactory input via the lateral entorhinal cortex.

The possibility that olfactory input is transmitted to specific subregions of the hippocampal formation via the entorhinal cortex was investigated electrophysiologically by analyzing the laminar profiles of potentials evoked in the hippocampal formation by stimulation of the lateral olfactory tract (LOT). LOT stimulation resulted in long latency (14--20 ms) evoked responses in the dentate gyrus of the hippocampal formation ipsilateral to the stimulation. The variable long latency of these responses and their inability to follow stimulus rates of 40/s suggested that these potentials reflected polysynaptic activation. Analysis of the laminar profiles of the evoked potentials indicated that the responses originated from a synaptic field localized in the outer portion of the stratum moleculare of the dentate gyrus, a terminal distribution which overlaps that of the lateral entorhinal cortical (LEC) projection to the dentate gyrus. Lesions of the LEC eliminated the long latency responses in the dentate gyrus evoked by LOT stimulation. In addition, a conditioning pulse delivered either to the LOT or to the LEC produced paired pulse potentiation of the response elicited by subsequent stimulation of the other structure. No evidence was found to indicate that responses were generated in regio superior of the hippocampus proper following LOT stimulation. Taken together, these results suggest that stimulation of the LOT activates the dentate gyrus of the hippocampal formation by multisynaptic pathways which relay through the lateral portion of the entorhinal area. This finding is discussed with regard to entorhinal cortical organization and the known olfactory projections to the LEC.

Animals↗
PubMed1978

Identification of the cells of origin of a central pathway which sprouts following lesions in mature rats.

Following unilateral destruction of the entorhinal cortical region of the adult rat, the denervated granule cells of the dentate gyrus are reinnervated as a result of the proliferation of a pathway from the surviving contralateral entorhinal area. The present study investigates the cells of origin of this lesion-induced pathway. Following HRP injections into the reinnervated dentate gyrus, heavily labeled cells were evident in layers II and III of the contralateral entorhinal area, in marked contrast to the pattern of labeling in normal animals, where labeled cells are restricted almost entirely to layer III. The atypically labeled cells in the operated animals were found predominantly in the dorsal half of the entorhinal area, and were concentrated in the medial most portion of layer II. These atypically labeled cells in layer II of the operated animals were an average of 16% larger than their unlabeled neighbors in the same lamina. This was not related to the loading with HRP, however, since in normal animals, cells in layer II which are labeled with HRP were no different in size than unlabeled cells. The atypically labeled cells in layer II of operated animals could also be identified at the electron microscopic level, and could be distinguished from the cells in layer III which normally project to regio superior of the contralateral hippocampal formation. While labeled cells were evident in layers II and III following injections into the reinnervated dentate gyrus, no labeled cells were found in the presubiculum or parasubiculum. In combination, these results suggest (1) the pathway which reinnervates the dentate gyrus from the contralateral entorhinal area originates predominantly, if not exclusively, from the cells in layer II, (2) these cells in layer II have the same preferential distribution within the entorhinal area as the rare lightly labeled cells which can be found contralateral to an injection in normal animals and (3) cells which participate in the reinnervation are larger than their unlabeled neighbors which presumably do not give rise to fibers which reinnervate the contralateral dentate gyrus. Since the cells in layer II which sprout following lesions can be identified at both the light and elctron microscopic level, a potentially valuable model system is available in which to analyze cellular changes during sprouting.

Animals↗
PubMed1978

Histochemical evidence for a post-lesion reorganization of cholinergic afferents in the hippocampal formation of the mature cat.

We have utilized acetylcholinesterase (AChE) histochemistry to analyze possible post-lesion changes in the distribution of AChE containing afferents to the hippocampal formation of the cat following unilateral destruction of the entorhinal cortex. In the cat, the entorhinal area gives rise to a massive projection to the ipsilateral fascia dentata, and to regio inferior and regio superior of the hippocampus proper. Sixty days following unilateral entorhinal lesions, histochemical preparations for AChE indicate a dramatic increase in the density of the reaction product in the zones normally occupied by entorhinal afferents in the fascia dentata and regio inferior of the hippocampus proper, whereas little if any increase in the density of the reaction product was observed in the entorhinal terminal zone in regio superior. In addition to these increases in the density of the AChE reaction product, there was also evidence for a widening of an AChE free zone in the inner stratum moleculare of the fascia dentata denervated by the lesion. The time course of these changes in the pattern of AChE staining was analyzed by sacrificing animals 7, 10, 13, 14, 16, 17,, 19, and 20 days following entorhinal cortical lesions. The increase in the density of the AChE reaction product in the denervated zones was not apparent at seven days post-lesion, while at ten days post-lesion, a slight increase in the density of the AChE reaction product could be observed. By 13 days post-lesion, the differences between the denervated and normally innervated (contralateral) hippocampal formation were prominent, and by 16 days post-lesion, the pattern of staining appeared comparable to that which was observed at longer post-lesion intervals. The present experiments indicate that following entorhinal cortical lesions in mature cats the final post-lesion pattern of altered AChE staining is quite comparable to that which is observed following similar lesions in rats. In the rat, such changes in AChE staining have been interpreted as a reflection of a proliferation of cholinergic septal afferents within the denervated zones. If this interpretation is correct, the present results suggest a similar proliferation of cholinergic afferents following entorhinal lesions in cats. The time course of this apparent proliferation is considerably slower in the cat then in the rat, however, since the earliest changes are observed at approximately five days post-lesion in the rat, and ten days post-lesion in the cat.

Acetylcholinesterase↗
PubMed1977

Quantitative autoradiographic analysis of the time course of proliferation of contralateral entorhinal efferents in the dentate gyrus denervated by ipsilateral entorhinal lesions.

The time course of the post-lesion proliferation of contralateral entorhinal afferents which occurs in response to ipsilateral entorhinal lesions was quanititatively analyzed with autoradiographic techniques. The extent of the crossed projection to the dentate granule cells was quantified on the basis of a contralateral/ipsilateral (C/I) ratio of grain density in the entorhinal terminal zones at 6, 8, 10, 12, 14, and over 60 days post-lesion. C/I ratios of grain density indicate little if any change in the crossed projection at 6 days post-lesion. Between 8 and 12 days post-lesion, the extent of the crossed projection increases dramatically, on the basis of the C/I ratio of grain density. C/I ratios do not increase further between 12 and 14 days post-lesion, but are higher at 60 days post-lesion. These results suggest that the crossed pathway proliferates extensively within the denervated zones between 8 and 12 days post-lesion, and may continue to proliferate at a much slower rate after 12 days post-lesion.

Animals↗
PubMed1977

Synaptic replacement in the dentate gyrus after unilateral entorhinal lesion: electron microscopic analysis of the extent of replacement of synapses by the remaining entorhinal cortex.

In response to a unilateral entorhinal lesion the input from the contralateral entorhinal cortex to the dentate gyrus appears to increase. We have studied this crossed projection by electron microscopy in normal animals and in animals one year or more after a unilateral entorhinal lesion. In normal animals few degenerating boutons are found after a contralateral entorhinal lesion. However, when the contralateral lesion was made one year after an ipsilateral entorhinal lesion, degenerating boutons were readily identified. The boutons were relatively few in number, but formed an abnormally large number of synaptic contacts. These results support the previous conclusion that fibres from the contralateral entorhinal cortex form additional synapses when their ipsilateral homologues are removed. However, these new cortical synapses probably account for only a small portion of those formed in response to the lesion. Thus an anatomically homologous input does not, in this case, selectively capture most of the newly available synaptic sites.

Animals↗
PubMed1976

Potentiation of excitatory synaptic transmission in the normal and in the reinnervated dentate gyrus of the rat.

Following destruction of the ipsilateral temporo-ammonic tract, which originates in the entorhinal cortex, and terminates on the granule cells of the dentate gyrus, fibers from the surviving contralateral entorhinal area proliferate forming extensive new connections with the denervated dentate granule cells. Utlizing extracellular recording techniques, we have compared the characteristics of synaptic transmission in the lesion induced afferents with the characteristics of the normal ipsilateral afferents by analyzing the responses of dentate granule cells to paired pulse activation of temporo-dentate circuitry. In the dentate gyrus of the normal rat, and extracellularly recorded EPSP evoked by stimulation of the ipsilateral entorhinal cortex is enhanced by as much as 100% by a "conditioning" pulse to the same afferent system. This is called paired pulse potentiation. In the reinnervated dentate gyrus, the extracellular EPSP evoked by a test stimulus delivered to the contralateral entorhinal cortex is also potentiated by a conditioning pulse. Thepaired pulse potentiation in the reinnervated dentate gyrus has a time course which is comparable to that of the normal ipsilateral afferent system, but the magnitude of the potentiation is somewhat less, averaging approximately 140% of control...

Afferent Pathways↗
PubMed1976

Reinnervation of dentate gyrus by homologous afferents following entorhinal cortical lesions in adult rats.

Granule cells of the rat dentate gyrus which are denervated by unilateral destruction of the entorhinal cortex are reinnervated in part by proliferation of surviving pathways from the contralateral entorhinal cortex. The cells of origin of these lesion-induced projections were identified by retrograde labeling with horseradish peroxidase and were the same cell type which normally project to the ipsilateral dentate gyrus

Afferent Pathways↗
PubMed1976

Cells of origin of entorhinal cortical afferents to the hippocampus and fascia dentata of the rat.

The pathway from the entorhinal cortical region to the hippocampal formation has previously been shown to be comprised of two sub-systems, one of which projects predominantly to the ipsilateral fascia dentata and regio inferior of the hippocampus proper, and a second which projects bilaterally to regio superior. The goal of the present investigation was to determine if these two pathways might originate from different cell populations within the entorhinal area. The cells of origin of these entorhinal pathways were identified by retrograde labeling with horseradish peroxidase (HRP). Injections which labeled the entorhinal terminal fields in both the fascia dentata and regio superior resulted in the retrograde labeling of two populations of cells in the entorhinal area. Ipsilateral to the injection, HRP reaction product was found in the cells of layer II (predominantly stellate cells) and the cells of layer III (predominantly pyramidal cells). Contralateral to the injections, however, the reaction product was found almost exclusively in the cells of layer III. With selective injections of the entorhinal terminal field in regio superior, only the cells of layer III were labeled, but these were labeled bilaterally. Selective injection of the entorhinal terminal field in the fascia dentata, however, resulted in the labeling of cells of layer II, but not of layer III, and these cells of layer II were labeled almost exclusively ipsilaterally. A very small number of labeled cells in layer II were, however, found contralateral to the injection as well. No labeled cells were found either in the presubiculum or parasubiculum following injections of the hippocampal formation. These cell populations were found capable of retrograde transport of HRP, however, since cells in both presubiculum and parasubiculum were labeled following HRP injections into the contralateral entorhinal area. These results suggest that the projections to the fascia dentata originate from the cells of layer II, while the projections to regio superior originate from the cells of layer III of the entorhinal region proper. The very slight crossed projection from the entorhinal area to the contralateral area dentata probably originates from the small population of cells in layer II which are labeled following HRP injections in the contralateral area dentata.

Afferent Pathways↗