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Showing papers on "Dentate gyrus published in 1977"


Journal ArticleDOI
09 Sep 1977-Science
TL;DR: Three-month-old rats were injected intraperitoneally with [3H]thymidine and labeled cells in the granular layers of dentate gyrus and olfactory bulb were confirmed as neurons by electron microscopy of reembedded 1-micrometer sections.
Abstract: Three-month-old rats were injected intraperitoneally with [3H]thymidine (4.3 microcuries per gram of body weight) and allowed to survive for 30 days. Radioautography of 1-micrometer sections revealed labeled cells in the granular layers of dentate gyrus and olfactory bulb; these were confirmed as neurons by electron microscopy of reembedded 1-micrometer sections.

1,495 citations


Journal ArticleDOI
TL;DR: It is concluded that regrowing cholinergic axons can be guided over large distances within the hippocampal formation, and that their patterning within the terminal fields is very precisely regulated by mechanisms released by deafferentation.
Abstract: Transplants containing developing cholinergic neurons were obtained from the septum-diagonal band area of rat fetuses and were implanted into a lesion of the septohippocampal cholinergic pathway or into a cavity of the occipital cortex in adult recipient rats. The growth of new cholinergic fibres from the implant into the hippocampal formation was followed with choline acetyltransferase (ChAT) determinations and acetylcholine esterase (AChE) histochemistry. A fimbrial lesion alone, transecting the septohippocampal pathway, caused an almost complete cholinergic denervation of the hippocampal formation that persisted throughout the five month experimental period. A septal transplant implanted into the cavity of the fimbrial lesion restored a new AChE-positive innervation pattern in the hippocampus and the dentate gyrus that closely mimicked the original innervation removed by the lesion. In parallel, there was a progressive recovery in the ChAT levels, starting in the septal end, and progressing in a temporal direction. A new cholinergic fibre supply could be established in the hippocampal formation also along an abnormal route, i.e. from the transplants implanted into a cavity in the occipital cortex (involving also the dorsal part of the entorhinal cortex). Provided the hippocampus previously had been denervated of its normal cholinergic innervation, a partly normal AChE-positive terminal pattern was thus re-established also from this abnormal position. If, on the other hand, the cholinergic afferents were left intact, the ingrowing fibres were restricted mainly to the outer portion of the dentate molecular layer, i.e. the terminal zone of the lesioned entorhinal perforant path fibres. This suggests that the growth of the sprouting AChE-positive fibres into the normal cholinergic terminal fields was blocked by the presence of an intact cholinergic innervation. It is concluded that regrowing cholinergic axons can be guided over large distances within the hippocampal formation, and that their patterning within the terminal fields is very precisely regulated by mechanisms released by deafferentation.

254 citations


Journal ArticleDOI
TL;DR: The time course of the recovery, the results following bilateral lesions, and the results of secondary lesions are all consistent with the hypothesis that recovery of alternation performance following unilateral E.C. lesions may depend upon the reinnervation of the dentate gyrus by the contralateral E. C.

239 citations


Journal ArticleDOI
TL;DR: Dorsal areas, however, required a greater number of stimulations to develop (“kindle”) a fully generalized convulsion than did ventral areas, except for the ventral dentate which had higher AD thresholds than ventral CAI.
Abstract: Electrodes were implanted to dorsal hippocampus (CA1), ventral CA1, DOrsal dentate gyrus or ventral dentate gyrus. Epileptiform afterdischarge (AD) thresholds were lower in dorsal areas than in ventral areas. Dorsal areas, however, required a greater number of stimulations to develop ("kindle") a fully generalized convulsion than did ventral areas. Thresholds and kindling rates in the dentate gyrus were intermediate between dorsal and ventral CA1, except for the ventral dentate which had higher AD thresholds than ventral CA1. Secondary sites within the hippocampus subsequently kindled within a few stimulations following completion of kindling in the primary site, regardless of which hippocampal area served as the primary site.

168 citations


Journal ArticleDOI
10 Jun 1977-Science
TL;DR: Measurement of the synaptic current at the dentate gyrus induced monosynaptically by stimulation of the angular bundle suggests that the mechanism by which gating occurs at this level is either a tonic inhibitory synaptic influence exerted upon the granule cells during the alert state, a tonics excitatory influence during slow-wave sleep, or both.
Abstract: Electrical stimuli were applied to the angular bundle of the freely moving rat, and the neuronal responses were recorded ipsilaterally in the dentate gyrus and the CA1 field of the hippocampus. The number of neurons responding monosynaptically in the dentate gyrus was relatively small when the animal was alert and not moving but was much greater both during slow-wave sleep and during rapid eye movement sleep. In Ca1, however, the trisynaptic population response was considerably smaller during rapid eye movement sleep and when the animal was alert than during slow-wave sleep. These findings are interpreted in terms of a set of behaviorally dependent "neural gates". Measurement of the synaptic current at the dentate gyrus induced monosynaptically by stimulation of the angular bundle further suggests that the mechanism by which gating occurs at this level is either a tonic inhibitory synaptic influence exerted upon the granule cells during the alert state, a tonic excitatory influence during slow-wave sleep, or both.

143 citations


Journal ArticleDOI
TL;DR: The entorhinal cortex of rats was removed at various times during development, and the reaction of the cholinergic septohippocampal input to the dentate gyrus was examined by use of acetylcholinesterase histochemistry.
Abstract: The entorhinal cortex of rats was removed at various times during development, and the reaction of the cholinergic septohippocampal input to the dentate gyrus was examined by use of acetylcholinesterase histochemistry. When the ipsilateral entorhinal cortex is completely removed, the outer 70-75% of the molecular layer of the dentate gyrus is almost completely denervated. After such a lesion at 5 to 33 days of age, the acetylcholinesterase staining initially intensified throughout the denervated area, indicating that the septohippocampal fibers branched or elongated. This reaction could be detected within one day after a lesion at 11 days of age and within three or five days after lesions at earlier or later times. Whereas the initial response of the septohippocampal fibers was independent of the age at which the lesion was made, their final localization depended on the developmental state of the animal. After lesions at the age of 5 or 11 days, the reactive septohippocampal fibers became restricted to the outer one-sixth to one-third of the molecular layer within two days after appearance of their initial reaction. A similar concentration of reactive fibers was demonstrable after lesions at 16, 18 or 21 days of age, but some reaction persisted in the middle third of the molecular layer. Finally, after lesions at 26 or 33 days of age the proliferating cholinergic fibers ultimately were uniformly distributed throughout the outer 60% of the molecular layer. These results suggest that septohippocampal fibers initially extend or sprout throughout the denervated area to replace the lost perforant path fibers. However, the reactive fiber population becomes restricted to the outer edge of the molecular layer if the entorhinal lesion is made before the period of cholinergic synaptogenesis and concentrates in this same zone if it is made while cholinergic synapses are forming. We suggest that either the proliferative reaction continues in the outer part of the molecular layer and subsides in other parts of the denervated area or septohippocampal fibers move outward through the molecular layer to assume a more superficial location. After entorhinal lesions at 16 days of age or later the pale-staining zone (containing fibers that originate in hippocampus regio inferior) immediately deep to the denervated area widened. If the lesion was made earlier, this zone never developed at most septotemporal levels of the dentate gyrus. These results are probably related to the extension of regio inferior fibers into the denervated area.

139 citations


Journal ArticleDOI
TL;DR: A quantitative morphological study of the changes in the dentate gyrus molecular layer in response to the removal of perforant path afferents was made utilizing electron microscopic techniques, with a major observation was an increase in intact bouton density in the region of denervation.
Abstract: A quantitative morphological study of the changes in the dentate gyrus molecular layer in response to the removal of perforant path afferents was made utilizing electron microscopic techniques. Alterations in 1. the population of remaining afferents, 2. glial cells, and 3. granule cell dendrites are reported. The major observation was an increase in intact bouton density in the region of denervation which began at 5 days post-lesion and continued through 11 days post-lesion, the longest post-lesion survival time studied.

130 citations


Journal ArticleDOI
TL;DR: The characteristic adult pattern of distribution of the terminals of the two hippocampo‐dentate pathways is established, and although this pattern is best accounted for on the basis of a temporal competition for the available synaptic sites on the proximal parts of the dendrites of the granule cells, the spatial segregation of these two fiber systems from those arising in the entorhinal cortex, is probably due to the selective fasciculation of fibers in each group of afferents.
Abstract: The development of the entorhinal, ipsilateral associational, and commissural afferents to the dentate gyrus have been studied autoradiographically, following the injection of small amounts of tritiated proline into the medial and lateral parts of the entorhinal cortex, and into fields CA3c and CA4 of the hippocampus, in a series of rats, on the third, sixth, and twelfth postnatal days. Clear labeling of the entorhinal afferents were found at the third postnatal day, and from the earliest stage studied the afferents from the two parts of the entorhinal cortex appear to be spatially segregated within the stratum moleculare of the dentate gyrus: the fibers from the lateral entorhinal area occupying the outermost one-third, or so, of this stratum, while those from the medial entorhinal cortex occupy its middle zone. The ipsilateral hippocampo-dentate associational pathway is present at the third postnatal day, but the commissural projection (which shares with it the inner part of the stratum moleculare) could not be labeled until the sixth postnatal day. By the twelfth day the characteristic adult pattern of distribution of the terminals of the two hippocampo-dentate pathways is established. Although this pattern is best accounted for on the basis of a temporal competition for the available synaptic sites on the proximal parts of the dendrites of the granule cells, the spatial segregation of these two fiber systems from those arising in the entorhinal cortex, is probably due to the selective fasciculation of fibers in each group of afferents and to their early cytochemical specificity.

116 citations



Journal ArticleDOI
TL;DR: The present report calls attention to a component of certain synaptic junctions which has received little attention since its description in 1962 by Westrum and Blackstad, found in dendritic spine synapses in rat telencephalon, and studies the distribution of synaptic spinules in the dentate gyrus of the hippocampus.
Abstract: The present report calls attention to a component of certain synaptic junctions which has received little attention since its description in 1962 by Westrum and Blackstad. This component, which we term the synaptic spinule, is found in dendritic spine synapses in rat telencephalon (e.g., hippocampus, caudate nucleus, temporal and frontal cortex). Its major feature is an invagination of the presynaptic terminal by the presynaptic membrane, with the postsynaptic membrane protruding into this invagination. The synaptic spinule occurs in close association with the post-synaptic density, often occurring between breaks in this specialization. Serial sections reveal that when a synaptic spinule is present, a spine apparatus is observed near the dendritic protrusion. Coated vesicles are sometimes observed associated with the synaptic spinule; in all such instances they are associated with the presynaptic membrane. We studied the distribution of synaptic spinules in the dentate gyrus of the hippocampus. In contrast to its presence in the molecular layer, the synaptic spinule has not been observed in terminals of the subgranular layer of the dentate hilus. It is speculated that the synaptic spinule may play a role in exchange of material at dendritic spine synaptic junctions.

102 citations




Journal ArticleDOI
TL;DR: The results indicate that the speed of growth and the distance covered by the regenerating ganglionic fibres within the hippocampus are regulated by mechanisms released by deafferentation.

Journal ArticleDOI
TL;DR: The 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 followinglesion.

Journal ArticleDOI
TL;DR: To determine whether the difference between immature and adult rats is attributable to an interaction with other reactive afferents, various portions of the entorhinal cortex were removed at the age of 11 days, and the cholinergic septohippocampal fibers were visualized by acetylcholinesterase histochemistry.
Abstract: It has been concluded previously that the septohippocampal fibers which project to the rat dentate gyrus extend or branch in the denervated area of the molecular layer following a complete ipsilateral entorhinal lesion. The septohippocampal fibers thus appear to replace some of the perforant fibers which degenerate as a result of the lesion. The reactive fibers eventually become localized to a much smaller and more superficial area after lesions of immature rats than after lesions made in adulthood. To determine whether this difference in the response results from a selective reaction to loss of the lateral perforant path in the immature rat, various portions of the entorhinal cortex were removed at the age of 11 days, and the cholinergic septohippocampal fibers were visualized by acetylcholinesterase histochemistry. An alternative possibility, that the difference between immature and adult rats is attributable to an interaction with other reactive afferents, was tested by removing other sources of input (the contralateral entorhinal cortex, contralateral hippocampal formation or both) along with the ipsilateral entorhinal cortex at the age of 11 days and then demonstrating the septohippocampal fibers histochemically. Lesions of the lateral part of the ipsilateral entorhinal cortex (source of the lateral perforant path) at 11 days of age evoked a septohippocampal reaction along the outer edge of the molecular layer, where the lateral perforant path fibers normally terminate. This result matched that produced by a complete entorhinal lesion. Lesions of the medial entorhinal cortex evoked no obvious reaction. In contrast, the septohippocampal fibers in adult rats proliferated in the denervated area of the molecular layer after lesions of either part of the entorhinal cortex. Combining lesions of other sources of innervation to the dentate gyrus with an ipsilateral entorhinal lesion at 11 days of age did not alter the response of septohippocampal fibers, as determined histochemically. Neither did the septohippocampal fibers react to removal of commissural afferents alone. The response at any age was unaffected by prior or subsequent removal of the contralateral entorhinal cortex. These results indicate that in immature rats the septohippocampal fibers respond only to loss of the lateral perforant path, but these same fibers can later react to loss of any part of the perforant path. They are regarded as support for the hypothesis that the reactive septohippocampal fibers preferentially interact with dendritic growth cones. Our results do not support explanations based on a hypothetical attraction between septohippocampal and crossed perforant path fibers (which react in the same area) or on competition with commissural fibers (which reinnervate an adjacent area). We suggest further that proximity to the degenerating elements does not in itself determine the pattern of reinnervation after lesions of the central nervous system.

Journal ArticleDOI
TL;DR: Results support the previous conclusion that fibres from the contralateral entorhinal cortex form additional synapses when their ipsilateral homologues are removed, but these new cortical synapses probably account for only a small portion of those formed in response to the lesion.
Abstract: 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.

Journal ArticleDOI
TL;DR: Transneuronal effects on mossy fiber synaptogenesis suggests that normally functioning entorhinal afferents to the granule cells are necessary for the normal development of dendritic spines in contact with hippocampal mossy fibers.
Abstract: The granule cell axons of the dentate gyrus (mossy fibers, MF) terminate with large, characteristic boutons on neurons of the regio inferior of the hippocampus. To study transneuronal effects on mossy fiber synaptogenesis, the entorhinal cortex, which is the source of the main afferent to the granule cells, was removed in 3-day old rats. After a postoperative survival time of 27 days, the animals were killed and the brain prepared for electron microscopy. No clear postlesional changes were observed in the inner structure of the presynaptic mossy fiber terminals. The mean size of MF boutons was roughly the same in the experimental animals as compared to normal, unoperated rats of the same age (4.19 μm2, SD 1.9; and 4.29 μm2, SD 2.2, respectively). On the postsynaptic side, however, some remarkable changes were found. In the operated animals, the number and total area of dendritic spines in synaptic contact with MF has significantly decreased in comparison with the controls. Also the size of a single spine in the operated animals was only 64 % of that in the normal. These changes were accompanied by a decrease in MF total perimeter and MF-dendritic contact length in the experimental animals. The length of the MF specialized synaptic contact was found to be correlated with the number and size of dendritic spines. Thus accordingly, though the length of the MF specialized contact with the dendritic shaft did not change, the absolute length of MF specialized contact with postsynaptic spines was decreased in the lesioned animals due to the numerical and size reduction of the spines. This suggests that normally functioning entorhinal afferents to the granule cells are necessary for the normal development of dendritic spines in contact with hippocampal mossy fibers.

Journal ArticleDOI
08 Sep 1977-Nature
TL;DR: A situation in which the dentate gyrus of the mammalian cerebral cortex offers a unique opportunity to test some of the hypotheses that may explain the selective termination of different afferents on restricted portions of the surface of a neurone is described.
Abstract: THE development of the central nervous system is characterised by the formation of specific synaptic connections. Highly selective connections form not only between classes of neurones, but also between specific neurones within classes. An additional degree of specificity is observed when the presynaptic axons contact only a limited portion of the target neurone. This kind of specificity is conspicuous in the dentate gyrus (fascia dentata) of the mammalian cerebral cortex. We describe here a situation in which the dentate gyrus offers a unique opportunity to test some of the hypotheses that may explain the selective termination of different afferents on restricted portions of the surface of a neurone.

Journal ArticleDOI
TL;DR: The TCA-PTA insoluble labelled glycoprotein was transported to the dentate gyrus in a significantly smaller amount and during a longer period of time in the senescent animals, which may reflect a reduction in amount and/or in rate of axonal transport of glycoproteins in the septo-hippocampal pathway of senescent rats.

Journal ArticleDOI
TL;DR: The results demonstrate that GABA is not released by entorhinal, commissural or mossy fiber projections and thus support the notion that in the hippocampal formation GABA is the transmitter only of short-axon interneurons, and suggest that GABAnergic boutons in the dentate gyrus increase their transmitter release capability after a bilateral entorHinal lesion.

Journal ArticleDOI
TL;DR: The results emphasize the close relationship between the extent and location of cell loss and the behavioral effects of prenatally induced brain damage.

Journal ArticleDOI
TL;DR: Data suggest a primary age-related change in the charg density of extracellular macromoledules, presumed to be primarily glycosaminoglycans, with a consequent change in water binding capacity and volume of theextracellular space.
Abstract: The volume of the extracellular space, which contributes to the microenvironment of neurons, is diminished in the brains of senescent (as compared to adult) rats and an age-related change in its composition has been hypothesized. To test this hypothesis we have compared the penetration of ruthenium red, a polyanion selectively distributed in the extracellular space, into the dentate gyri of young adult and senescent Fischer 344 rats. Slices of hoppocampal formation were fixed by immersion, first in a glutaraldehyde solution containing ruthenium red, then in a solution of osmium tetroxide containind examined by electron microscopy. Dense particles of ruthenium red reaction product were readily localized in intercellular channels and synaptic clefts and the depth of penetration of ruthenium red in 25-month-old rats, as compared with 3-month-old animals, was found. These data indicate an age-related change in the charge density of the intercellular channels in the dentate gyrus of 25-month-old rats. They suggest a primary age-related change in the charg density of extracellular macromoledules, presumed to be primarily glycosaminoglycans, with a consequent change in water binding capacity and volume of the extracellular space.

Journal ArticleDOI
TL;DR: This investigation provides a calibration for the reduced silver method which has been used to trace developing axons and shows the first signs of Wallerian degeneration, after cutting axons in the perforant path, were seen in the dentate neuropile at 9 days.
Abstract: The development of the projection from the entorhinal cortex to the dentate gyrus (perforant path) has been studied with the electron microscope. The projection was lesioned in baby rats 5--13 days old and the dentate gyrus examined after 6--72 hr. Degenerating synapses first appeared in small numbers in the dentate neuropile at 7 days and in greater numbers in progressively older animals. There was a sixteen-fold increase in the number of synapses undergoing degeneration between 7 and 13 days. This investigation provides a calibration for the reduced silver method which has been used to trace developing axons (Singh, 1977). By this method the first signs of Wallerian degeneration, after cutting axons in the perforant path, were seen in the dentate neuropile at 9 days.

Journal ArticleDOI
TL;DR: Thyroid-hormone treatment did not affect significantly the postnatal cell formation of the dentate gyrus, but resulted in the appearance of a great number of pycnotic cells in the granular layer.
Abstract: The postnatal development of the dentate gyrus and the effect of 5 μg/day triiodothyronine treatment was examined by means of tritiated thymidine autoradiography.

Journal ArticleDOI
TL;DR: In chloralose‐anesthetized cats, the suppression of extralemniscal thalamic units by the dorsal and ventral hippocampus was investigated through interaction with conditioning electrical stimulation in different regions around the hippocampal arch, including the parahippocampal gyrus.
Abstract: In chloralose-anaesthetized, Flaxedil-paralysed cats, the suppression of extra-lemniscal thalamic units by dorsal and ventral hippocampus was investigated. Unitary responses to test somatic stimuli, recorded in centrolateral and neighbouring thalamic nuclei, were interacted with conditioning electric stimulation in different regions around the hippocampal arch, including parahippocampal gyrus (entorhinal and retrosplenial areas). Stimulation of dorsal (dhc) and ventral (VHC) hippocampus suppressed roughly equal proportions of responses. However, within each of DHC and VHC, effectiveness depended on the region stimulated. In DHC, fields CA1 and CA3, subiculum (SUB), and retrosplenial area, but not field CA4 or dentate gyrus, usually suppressed extralemniscal units at currents below 1.0 mA. In VHC, the most effective regions were entorhinal cortex, CA3, and CA4 with dentate gryus (FD), while stimulation of CA1 or subiculum was almost ineffective, at currents below 1.0 mA. In VHC, the regions were ranked for effectiveness: Entorhinal cortex=CA3 is greater than FD is greater than SUB is greater than CA1. No topographic relationship was found between hippocampal region and thalamic loci for unit suppression. Lemniscal-type unit responses in ventrobasal thalamus were unaffected by stimulation of the hippocampus or parahippocampal gryus. Interruption of the fornix-fimbria system prevented suppression elicited from CA1 of DHC, or from CA3 but not FD of VHC. It had no effect on suppression elicited from retrosplenial or entorhinal cortex. Hippocampal regional variation of effectiveness in suppressing extralemniscal pathways may contribute to the differential behavioural involvements reported for different hippocampal structures.