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M Frotscher

Publications and source records attributed to M Frotscher.

At least 109 records · Page 6Linked to original sources
PubMed1995

Morphological evidence for the sprouting of inhibitory commissural fibers in response to the lesion of the excitatory entorhinal input to the rat dentate gyrus.

Recently a commissural fiber projection that terminates in the outer molecular layer of the fascia dentata was described in normal rats (Deller et al., 1995). In the present article, Phaseolus vulgaris leucoagglutinin (PHAL) tracing was used to analyze the contribution of this previously unknown projection to the commissural sprouting response after entorhinal cortex lesion. Rats 4-8 weeks after unilateral entorhinal lesion received a single PHAL deposit into the hilus of the fascia dentata contralateral to the lesion side. Unlesioned control animals received a similar PHAL deposit. The degree of axonal arborization and the bouton density per axon length were determined for individual PHAL-labeled commissural axons to the outer molecular layer of the dentate gyrus. A significant increase in both parameters was observed in the lesioned group. The PHAL-labeled commissural fibers established symmetric synapses in the denervated outer molecular layer. Postembedding immunocytochemistry indicated that some of these sprouting commissural fibers are GABAergic. Our findings provide morphological evidence for lamina-specific sprouting of an inhibitory commissural projection that normally terminates in the outer molecular layer. This suggests that inhibitory fibers participate in the replacement of the excitatory perforant pathway after entorhinal lesion.

Afferent Pathways↗
PubMed1995

Understanding the cortex through the hippocampus: lamina-specific connections of the rat hippocampal neurons.

A characteristic feature of hippocampal organisation is the lamina-specific termination of afferent fibres. The factors determining this characteristic fibre segregation are not known. By using slice cultures as a model, we have recently demonstrated that the laminated termination of hippocampal afferents does not result from the temporal sequence of ingrowth of the various afferent fibre systems during development. Moreover, the lack of extrinsic afferents in culture does not induce a substantial translaminar sprouting of the remaining (intrinsic) fibres or of a defined afferent system supplied by a coculture. These results contrast with previous reports on an expansion of intact fibre systems in the hippocampus in response to partial deafferentation, for instance by removal of entorhinal afferents. We therefore studied the sprouting of commissural fibres following an entorhinal lesion directly by labelling commissural axons in vivo with the anterogradely transported tracer Phaseolus vulgaris leucoagglutinin. Sprouting of commissural fibres following an entorhinal lesion was observed but, in accordance with our in vitro observations, this growth of commissural terminals took place within the appropriate termination zones of commissural fibres. These results point to a rigid laminar specificity of hippocampal afferents that is preserved after partial deafferentiation.

Animals↗
PubMed1994

Associational and commissural afferents of parvalbumin-immunoreactive neurons in the rat hippocampus: a combined immunocytochemical and PHA-L study.

Nonpyramidal neurons containing the calcium-binding protein parvalbumin (PV) are one of the inhibitory elements of the hippocampal network. Previous studies have indicated that they are involved in septohippocampal disinhibitory circuits. This study analyzes the commissural and ipsilateral associational afferents of parvalbumin neurons. Injections of the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L) into the hilus of the fascia dentata labeled numerous axons in the molecular layer that established synaptic contacts with parvalbumin-immunoreactive neurons on both the injection and the contralateral side. Mossy fibers, labeled by injections into the granule cell layer, terminated on parvalbumin neurons in the hilus and in CA3. Injections of PHA-L into CA3 resulted in a dense labeling of fibers in the hilus and in CA3, CA2, and CA1 on both the injection and the contralateral side. In all these hippocampal fields, PHA-L-labeled fibers established asymmetric contacts with PV-immunoreactive, presumably GABAergic, inhibitory neurons. These observations indicate that parvalbumin-immunoreactive inhibitory neurons in the hippocampus are targets of presumably excitatory associational and commissural projections and suggest that they are involved in feed-forward and feed-back circuits.

Animals↗
PubMed1994

Fine structure of rat septohippocampal neurons. III. Recovery of choline acetyltransferase immunoreactivity after fimbria-fornix transection.

Most cholinergic projection neurons in the medial septal nucleus (MS) lose their capability to synthesize choline acetyltransferase (ChAT) after axotomy by bilateral fimbria-fornix transection. We have recently shown that identified septohippocampal neurons survive axotomy up to 10 weeks and display fine-structural characteristics of cells in control rats. However, the fate and functional role of these neurons remained unclear. Here we describe observations made in rats which survived axotomy for 6 months. Adult Sprague-Dawley rats were subjected to bilateral transection of the fimbria-fornix system. In some animals septohippocampal projection neurons were labeled by the retrograde fluorescent tracer Fluoro-Gold (FG) prior to axotomy. After varying survival times following fimbria-fornix transection, the animals were fixed and sections of the septal region immunostained for ChAT. Three weeks postlesion, the number of ChAT-positive cells in the MS was reduced to 19% of control, suggesting a severe neuronal loss. However, 10 weeks and 6 months after axotomy this value increased to 28% and 54%, respectively. Fine-structural analysis of ChAT-positive neurons after 6 months survival revealed all characteristics of vital cells including normal input synapses. The majority of these cells could be identified as former septohippocampal projection neurons by the presence of FG. We conclude that many neurons in the MS have the capacity to restore their transmitter synthesis in a long-lasting process following axotomy.

Animals↗
PubMed1994

Transient dendritic appendages on differentiating septohippocampal neurons are not the sites of synaptogenesis.

The factors which determine the final shape and synaptic connections of a neuronal phenotype are largely unknown. In adult animals, a large number of projection neurons, e.g. cortical pyramidal neurons, bear spines which, in the case of pyramidal cells, are postsynaptic elements of mainly asymmetric synapses. In contrast, mature septohippocampal neurons do not bear spines. During maturation, however, septohippocampal projection neurons develop a variety of dendritic appendages. Because the appearance of these processes falls into the period of synaptogenesis, it has been hypothesized that these transient appendages may be the site of synaptogenesis. Here we have investigated whether these transient dendritic appendages are the site of initial synaptic contacts of septohippocampal neurons. Septohippocampal projection neurons in late embryonic and early postnatal rats were identified by retrograde tracing with the carbocyanine dye DiI or biocytin. Subsequently, selected cells were processed for electron microscopy. Serial thin sections through identified dendritic appendages did not reveal synaptic contacts with presynaptic boutons but immature to mature synapses were always found on dendritic shafts or somata. Often, synapses are located close to the appendages. These data indicate that the transient appendages are not the place where ingrowing afferent fibers make their synapses. The available information about transient dendritic appendages suggests, that they may be involved in short-term contacts with ingrowing axons, without being themselves the final site of the synaptic contact.

Aging↗
PubMed1994

Survival and transmitter expression of rat cholinergic medial septal neurons despite removal of hippocampus in the early postnatal period.

It has been shown that target-derived neurotrophins are not necessary for the survival of septohippocampal cholinergic neurons in adult rats. In this study, we have removed the hippocampus in early postnatal rats by unilateral excitotoxic N-methyl-D-aspartate lesions at postnatal days 5, 10 and 20. At postnatal day 70, numerous cholinergic neurons (60% of controls) were present in the medial septum on the lesioned side. This suggests that there is only a limited influence of target-derived neurotrophic factors to these cells also in development.

Animals↗
PubMed1994

Dendritic development of dentate granule cells in the absence of their specific extrinsic afferents.

Dendrites and spines are postsynaptic structures that develop in association with presynaptic fibers. Recent studies have shown that granule cells of the fascia dentata survive in slice cultures and differentiate in a manner known from in situ studies. However, all extrinsic afferent fibers are absent under culture conditions. In the present study, we study whether dendrites and spines of granule cells in slice cultures differentiate normally, although they are not contacted by their normal layer-specific afferents. Slices of hippocampus were prepared from rat pups at the day of birth. After 5, 10, 15, and 20 days of incubation, granule cells in these cultures were Golgi impregnated. For comparison, perfusion-fixed hippocampal sections of 5-, 10-, 15-, and 20-day-old rats were impregnated the same way. Our results show that the total density of spines on granule cell dendrites in culture increased as in perfusion-fixed animals. However, after 20 days of incubation, the absolute number of dendritic spines on cultured neurons was reduced because of a reduction of peripheral dendrites. This reduction was accompanied by an increase in the number of stem dendrites originating from the perikaryon. The density of spines on these proximal dendrites was larger in cultured granule cells than in controls. Our results suggest that the lack of major extrinsic (entorhinal) afferents that normally terminate on peripheral granule cell dendrites causes retraction of these dendrites. At the same time, there is growth of proximal dendritic portions. Proximal dendrites are targets of associational fibers, which are known to sprout under these culture conditions.

Animals↗
PubMed1994

Is there a long-lasting effect of a short-term nerve growth factor application on axotomized rat septohippocampal neurons?

Loss of choline acetyltransferase (ChAT)-immunoreactive neurons in the medial septum (MS) following fimbria transection can be prevented by nerve growth factor (NGF) application. Here we have studied the long-term effects of a short-term NGF treatment starting immediately after lesion and lasting for the first 3 weeks. We demonstrate that this NGF treatment rescues many ChAT neurons after short survival time (3 weeks) but does not have a long-lasting (6 months) effect on both ChAT- and parvalbumin-immunopositive (GABAergic) MS neurons.

Animals↗
PubMed1994

Expression of the cholecystokinin gene in rat hippocampal interneurons is independent of extrinsic input.

In the present study we have used slice cultures of hippocampus and in situ hybridization techniques in order to study the ability of hippocampal neurons to synthesize CCK mRNA in the absence of extrinsic afferents. Our results show that very similar types of hippocampal neurons express CCK mRNA in culture as in situ. We conclude that the expression of the CCK gene in hippocampal neurons is not dependent on extrinsic afferent input.

Animals↗
PubMed1994

Reciprocal connections of lateral septal neurons and neurons in the lateral hypothalamus in the rat: a combined phaseolus vulgaris-leucoagglutinin and Fluoro-Gold immunocytochemical study.

Reciprocal connections between lateral septal neurons and neurons in the lateral hypothalamus/lateral preoptic area were studied in the rat. The anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) and the retrograde tracer Fluoro-Gold (FG) were simultaneously injected into the lateral septum. After double-immunocytochemistry, PHA-L-labeled terminals were found in synaptic contact with dendrites of retrogradely FG-labeled neurons in the lateral hypothalamic/lateral preoptic area.

Afferent Pathways↗
PubMed1994

Mossy cells of the rat fascia dentata are glutamate-immunoreactive.

The mossy cells represent a prominent cell type of the hilar region. Whereas the morphology of these neurons, their synaptic connections, and physiological characteristics have been described in some detail, information about their neurotransmitter is still lacking. Using immunocytochemistry in combination with Golgi impregnation, the authors demonstrate that identified mossy cells are GABA-immunonegative but stain for glutamate. These results do not prove that these cells use glutamate as a transmitter, since glutamate is a ubiquitous metabolite. However, together with the lack of GABA staining and a recent report on asymmetric spine synapses formed by identified mossy cell axons, the present results support an excitatory nature of these neurons.

Animals↗
PubMed1994

Divergence of hippocampal mossy fibers.

By connecting the fascia dentata with the hippocampus proper, the axons of the granule cells, the mossy fibers, represent an important element of the main excitatory, trisynaptic pathway of the hippocampal formation. In this review the various synaptic connections of the mossy fibers are discussed. It turns out that the mossy fibers do not only establish synapses with the pyramidal neurons of regio inferior as traditionally assumed, but a variety of local circuit neurons as well as projection cells are also contacted by the mossy fibers. Thus there is an underestimated divergence of the impulse flow within the "trisynaptic" pathway at the level of the mossy fibers. Similarly, the pattern of afferent input to the granule cells, especially that of GABAergic neurons, is more complex than previously assumed. In this respect the concept of a unidirectional "trisynaptic" pathway certainly is an oversimplification. In particular, the hilus of the fascia dentata, that the mossy fibers traverse on their way to regio inferior, is often neglected in this concept. The hilar region comprises a large variety of morphologically and functionally distinct neuronal types that, to a large extent, are targets of hilar mossy fiber collaterals. By focusing on the mossy fiber system, an attempt is made in this review to summarize new data on hippocampal circuitries that have been accumulated since the original description of the trisynaptic pathway. This concept, which originally comprised the synapses of the perforant path fibers on dentate granule cells, the mossy fiber synapses on CA3 pyramidal neurons, and the synapses of the Schaffer collaterals on CA1 pyramidal cells, has been of great heuristic value but needs to be modified in view of recent morphological and physiological data.

Animals↗
PubMed1994

Distribution and morphological characteristics of oligodendrocytes in the rat hippocampus in situ and in vitro: an immunocytochemical study with the monoclonal Rip antibody.

Oligodendrocytes in the rat hippocampus in situ and in organotypic slice cultures were studied by light and electron microscopic immunocytochemistry using the monoclonal Rip antibody. Our results confirm that this antibody exclusively stains oligodendrocytes, while astrocytes and neurons are not labelled. In the light microscope, immunopositive cells had the appearance of myelinating oligodendrocytes with their characteristic tubular processes. In the electron microscope, stained cells showed intimate contacts with myelin sheaths but not with the basal laminae of endothelial cells. Rip-positive oligodendrocytes were unevenly distributed in the adult rat hippocampal formation. In general, they were abundant in layers known to contain many afferent and efferent fibres. In the hippocampus proper, there was a particularly strong immunolabelling of stratum radiatum of field CA2. In the fascia dentata, the hilar region displayed a high cell density, especially in the vicinity of the granule cell layer. A similar distribution of immunopositive cells was found in young animals (15-18 days old); however, the density of labelled cells was lower, particularly in the hilus. Immunolabelled cells in slice cultures of hippocampus displayed the characteristics of myelinating oligodendrocytes. Moreover, they showed an organotypic distribution, although afferent and efferent fibre projections normally myelinated by these cells were absent under these conditions.

Animals↗
PubMed1994

Development of granule cells, and afferent and efferent connections of the dentate gyrus after experimentally induced reorganization of the supra- and infrapyramidal blades.

We have analyzed the development of the major afferent and efferent connections of the hamster dentate gyrus as well as the morphology of its granule cells, subsequent to a novel developmental defect. Following the selective destruction of the overlying meningeal cells by the neonatal administration of 6-hydroxydopamine, the majority of the glial and neuronal precursor cells destined for the infrapyramidal blade of the dentate gyrus are redirected into the suprapyramidal stratum granulosum, that subsequently becomes elongated and thickened. The remaining cells form a rudimentary infrapyramidal blade with a temporal delay of at least one week, the molecular layer of which is reduced in comparison to controls. This rudiment is either attached to the suprapyramidal blade by an apparently normal crest region or develops as a separate structure. Consecutive to this manipulation, the terminal field of the early-differentiating commissural and associational fibers expands in the suprapyramidal blade, whereas it is reduced in the late-forming infrapyramidal rudiment, the vacant space at the granule cell dendrites being taken over by entorhinal afferents. The efferent mossy fiber bundle does not show any differences along its course into the CA3 region, whereas hilar mossy fibers expand their intragranular distribution, sometimes contacting, but never invading the molecular zone. The morphology of the majority of the granule cells is entirely normal, however, a small but significant proportion maintains additional basal dendrites normally present only in immature, but not in adult rodents.

Animals↗
PubMed1994

Distribution of calbindin D28k immunoreactive cells and fibers in the monkey hippocampus, subicular complex and entorhinal cortex. A light and electron microscopic study.

Calbindin D28k (CB)-containing neurons and axon terminals in the hippocampus, subicular complex and entorhinal cortex of the African green monkey (Cercopithecus aethiops) were studied by light and electron microscopic immunocytochemistry. CB was present in granule cells of the dentate gyrus, pyramidal neurons of hippocampal fields CA1 and CA2, and in pyramidal neurons of the prosubiculum and entorhinal cortex. In contrast, pyramidal neurons in the CA3, subiculum and presubiculum were not labeled. A subpopulation of non-principal neurons (non-granule and non-pyramidal cells) was also stained for CB. These cells were rare in the hippocampus and subiculum, but were more frequently observed in the presubiculum, parasubiculum, and in the entorhinal cortex. In the electron microscope, these non-principal cells displayed fine-structural characteristics of GABAergig neurons. Strongly stained CB-immunoreactive bundles of myelinated axons were found in the molecular layer of the subiculum and in various layers of the presubiculum. The CB-positive, unmyelinated axons of the granule cells, the mossy fibers, gave rise to distinct fiber bundles. Mossy fiber terminals formed asymmetric synapses on large spines in the hilus and CA3. In addition to the giant mossy fiber boutons, there were large CB-positive terminals that formed asymmetric synapses with dentritic spines throughout the hippocampal formation. These boutons also formed axo-dendritic synapses in the entorhinal cortex. Axon terminals that formed symmetric synapses and might, thus, be derived from non-principal neurons, were rarely found in the hippocampus and subicular complex. They were more frequent in the parasubiculum and entorhinal cortex. These CB-positive terminals were small, heavily immunostained, and formed symmetric axo-dendritic synapses. Our results demonstrate a great diversity of CB-containing neurons, axons, and terminals in the monkey hippocampal formation. In general, regions that received a dense innervation of CB-positive terminals displayed pyramidal neurons that all lacked this calcium-binding protein. Further studies are required to understand the functional significance of these findings.

Animals↗
PubMed1993

Chandelier cells in the hippocampal formation of the rat: the entorhinal area and subicular complex.

In the present study we describe the characteristics of the chandelier cells in the rat entorhinal cortex and subicular complex by using the Golgi method and combined Golgi-electron microscopic techniques. In the entorhinal cortex, chandelier cells were frequently stained in layers II/III. Two types of axonal complexes were noted. One had a preferential horizontal orientation and gave rise to terminals located in the upper portion of layers II/III. The second type of chandelier cell axon was observed in the medial entorhinal area, innervating the entire extent of layers II/III. In the subicular complex, chandelier cells were frequently stained in the parasubiculum, whereas only a few cells were found in the presubiculum. In both subfields, chandelier cell axons were restricted to layers II/III. In the subiculum, most chandelier cells were present in the stratum radiatum, giving rise to a descending axon that branched in the stratum pyramidale. Both the size and morphological features of the chandelier cell terminal portions were found to be region-specific. Electron microscopically, the cell body and dendrites of gold-toned chandelier cells displayed typical features of nonpyramidal cells, such as the presence of nuclear infoldings, symmetric and asymmetric synapses on the cell body, and moderate numbers of axon terminals covering the smooth dendritic surface. Five gold-toned chandelier cell axonal complexes were analyzed at the fine structural level. In all parahippocampal regions, gold-labeled axon terminals formed symmetric synaptic contacts with axon initial segments. Our results demonstrate the presence, morphological characteristics, and target selectivity of identified chandelier cells in the parahippocampal region of the rat. Together with previous data, these results suggest a wide distribution of this specialized type of cortical interneuron and indicate that it is a constant and essential component of inhibitory circuits in the cerebral cortex. The possible significance of chandelier cells for the circuits linking several subfields of the hippocampal formation is discussed.

Animals↗
PubMed1993

Formation of layer-specific fiber projections to the hippocampus in vitro.

The factors determining the layer-specific termination of hippocampal afferents are not known. Previous studies have suggested that the laminated termination of afferent fiber systems is caused by their sequential ingrowth during development. Here we have tested this temporal hypothesis of fiber segregation by an in vitro confrontation system in which the sequential arrival of entorhinal and commissural fibers was reversed. However, despite the temporal reversal of ingrowth, both fiber systems terminated in their normal positions. We conclude that the sequence of fiber ingrowth does not determine the lamination of hippocampal afferents.

Afferent Pathways↗