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M Frotscher

Publications and source records attributed to M Frotscher.

At least 181 records · Page 10Linked to original sources
PubMed1988

Fine structure of identified neurons in the primate hippocampus: a combined Golgi/EM study in the baboon.

The hippocampi of two 1-year-old female baboons (Papio anubis) were used for a combined Golgi/electron microscope (EM) study of characteristic cell types in the hippocampus proper and fascia dentata. Results were compared with previous Golgi/EM studies of hippocampal neurons in small laboratory animals. Cell bodies of pyramidal neurons in CA1 were more loosely distributed than known from studies on the rat or guinea pig. Numerous basal and horizontal dendrites originating from the perikaryon filled in the space between neighboring cell bodies. Apical stem dendrites were varying in length, depending on the position of the parent cell body in outer or inner portions of the pyramidal layer. Dendrites were densely covered with spines which in the EM showed very complex synaptic contacts. In contrast to our observations in rats and guinea pigs, CA3 pyramidal cells in the monkey hippocampus exhibited numerous large spines or excrescences not only on apical dendrites but also on basal dendrites running through stratum oriens. These excrescences appeared to be more complex than in small rodents. They often branched, protruding deeply into presynaptic mossy fiber boutons, and formed multiple asymmetric synaptic contacts. Granule cells of the monkey fascia dentata, in contrast to those of the rodent, occasionally had basal dendrites extending into the hilar region. In the EM, granule cells either with or without basal dendrites exhibited fine structural characteristics that were very similar to those described in Golgi/EM studies of granule cells in the rat fascia dentata. Of the various types of nonpyramidal neurons the horizontal cells in stratum oriens with dendrites parallel to the alveus were analyzed. As seen in rats, these cells exhibited large amounts of rough endoplasmic reticulum, indentations of the nuclear membrane, and nuclear inclusions. Numerous terminals formed synaptic contacts on dendritic shafts. In contrast to rodents, numerous spines arose from dendrites and cell bodies of these neurons. In the EM, often single spines were found to establish synaptic contacts with several presynaptic boutons. In summary, our correlated light and EM study of four characteristic cell types, which are present in both nonprimates and primates, demonstrates a much more complex dendritic pattern and synaptic organization of these neurons in primates than in commonly studied small laboratory animals.

Animals↗
PubMed1988

Cholinergic neurons in the rat hippocampus do not compensate for the loss of septohippocampal cholinergic fibers.

In recent studies a small number of choline acetyltransferase (ChAT)-immunoreactive, supposedly cholinergic, neurons intrinsic to the rat hippocampus have been described. Here we report that these neurons are not capable of sprouting in response to removal of the cholinergic input to the hippocampus from the medial septum/diagonal band complex. One month after unilateral transection of the fimbria-fornix an almost complete lack of cholinergic fibers persists in all layers of the dorsal hippocampus and fascia dentata ipsilateral to the lesion when compared to the contralateral hippocampus or to unlesioned control rats. These results indicate that the well-known phenomenon of collateral sprouting in response to partial deafferentation is a specific process that spares a distinct group of cholinergic cells in the rat hippocampus.

Animals↗
PubMed1988

Catecholaminergic innervation of pyramidal and GABAergic nonpyramidal neurons in the rat hippocampus. Double label immunostaining with antibodies against tyrosine hydroxylase and glutamate decarboxylase.

This study describes the catecholaminergic innervation of rat hippocampal neurons at the electron microscopic level by using an antibody against tyrosine hydroxylase (TH) and immunocytochemical techniques. In a first series of experiments, the course and distribution as well as the synaptic contacts of TH-immunoreactive fibers were analyzed with the peroxidase-antiperoxidase (PAP) method. Next, peroxidase immunostaining of TH fibers was combined with glutamate decarboxylase (GAD) immunostaining, using avidinated ferritin as a second electrondense marker. Our results demonstrate that TH-immunostained terminals establish asymmetric synaptic contacts with spines of pyramidal neurons, and symmetric synaptic contacts with cell bodies and dendritic shafts of ferritin-labeled GAD-immunoreactive nonpyramidal cells.

Animals↗
PubMed1988

CCK-immunoreactive terminals form different types of synapses in the rat and monkey hippocampus.

Electronmicroscopic immunocytochemical analysis of the types and patterns of synaptic contacts formed by cholecystokinin (CCK)-containing terminals in the CA1 and CA3 region of the rat and monkey hippocampus reveals numerous symmetric synaptic contacts on cell bodies and dendritic shafts of pyramidal cells in both species. In the monkey, however, CCK-immunoreactive terminals also form asymmetric synaptic contacts with dendritic spines, such contacts are absent or very rare in the rat hippocampus. The present finding in primate hippocampus provides evidence that the same neuropeptides can be found in both symmetric and asymmetric contacts and may be added to other evidence challenging the traditional concept that symmetric synapses mediate exclusively inhibitory and asymmetric exclusively excitatory transmission. Furthermore, although our comparative analysis confirms considerable similarities in the distribution of CCK-containing elements in primate and rodent hippocampus it also revealed a potentially important difference in synaptoarchitecture that should be taken into account in extrapolations from one species to the other.

Animals↗
PubMed1988

Differentiation of granule cells in relation to GABAergic neurons in the rat fascia dentata. Combined Golgi/EM and immunocytochemical studies.

Golgi impregnation was used to study the dendritic differentiation of granule cells in the rat fascia dentata. The impregnated granule cells were gold-toned allowing for a fine structural study of the same identified neurons and of the input synapses onto their cell bodies and dendrites. Due to the long postnatal formation of these cells it was possible to describe a sequence of maturational stages coexisting on the same postnatal day (P5). Characteristic features of the dendritic development of granule cells were i) occurrence of varicose swellings along the dendrites, ii) growth cones on dendritic tips, iii) transient formation of basal dendrites, and iv) progressive development of dendritic spines. Incoming synapses on the differentiating granule cells were mainly found on dendritic shafts. Their membrane specializations were symmetric. At least some of these symmetric synapses were GABAergic because immunostaining of Vibratome sections from the same postnatal stage (P5) demonstrated a well-developed GABAergic axon plexus in the fascia dentata (antibodies against glutamate decarboxylase (GAD), the GABA synthesizing enzyme). Electron microscopy of the immunostained axon plexus revealed numerous GABAergic terminals that formed symmetric synaptic contacts, mainly on shafts of differentiating dendrites but also on cell bodies of granule cells. Our results thus indicate that the plexus of inhibitory GABAergic axons is already well developed at a stage when the target neurons, the granule cells, are still being formed.

Animals↗
PubMed1988

Synaptic organization of intracellularly stained CA3 pyramidal neurons in slice cultures of rat hippocampus.

Pyramidal cells of regio inferior in slice cultures of the rat hippocampus were impaled and intracellularly stained with horseradish peroxidase. A correlated light- and electron-microscopic analysis was then performed to study the properties of these neurons under culture conditions with particular emphasis on input synapses onto these cells. Like pyramidal cells in situ, CA3 pyramidal neurons in slice cultures had a triangular cell body with an apical stem dendrite emerging from it. Several basal dendrites and the axon arose from the basal pole of the cell body. The peripheral thin branches of both apical and basal dendrites were covered with small spines, whereas proximal thick dendritic segments and portions of the cell body exhibited large spines or excrescences. The axon gave off numerous fine varicose collaterals which projected to stratum radiatum of CA1 (Schaffer collaterals), to the alveus and to the hilar region. In one case a collateral could be followed to stratum moleculare of the fascia dentata. Electron-microscopic analysis of the injected pyramidal neurons revealed that their cell bodies, dendritic shafts and spines formed synaptic contacts with presynaptic terminals. Mossy fiber endings were identified by their large size and their numerous clear synaptic vesicles with some dense-core vesicles intermingled, and were observed to form synaptic contacts on the large spines or excrescences. Since extrinsic afferents degenerate in slice cultures, the numerous synaptic boutons on the identified pyramidal neurons probably arise from axons of intrinsic neurons that have sprouted in response to deafferentation. This assumption is supported by the finding that collaterals of the injected neurons formed abundant synaptic contacts on dendritic shafts and spines of other cells. These results suggest that, although pyramidal cells under culture conditions retain a remarkable number of their normal characteristics, considerable synaptic reorganization does take place.

Action Potentials↗
PubMed1988

Ultrastructural localization of calcium in the myocardium of cardiomyopathic syrian hamsters.

Cardiomyopathy of the Syrian hamster is characterized by myocardial calcium overload and focal myocardial necrosis. The cause of the myocardial calcium overload is not yet fully understood. In this study, the ultrastructural localization of calcium was determined in normal hamster hearts and in non-necrotic and necrotic myocardium of cardiomyopathic hamsters (strain BIO 82.62). In many cells from the non-necrotic myocardium of the cardiomyopathic hamsters the calcium deposits, visible as 20 nm particles, were confined to the inner leaflet of the plasma membrane, the T-tubules and the intercalated disks. This corresponds to the calcium distribution found in normal hamsters and other mammalian species. A number of morphologically normal cells, however, displayed an increased amount of calcium precipitate in the mitochondria as well as at the sarcolemma indicating that, in the cardiomyopathic hamster, focal calcium overload is detectable cytochemically in cells which otherwise do not show gross abnormalities. In cells showing morphological signs of myolytic degeneration a marked redistribution of calcium precipitate took place. Sarcolemma became devoid of calcium deposits whereas an enormous amount of clustered precipitate occurred in largely swollen mitochondria. These data are in support of a relationship between impaired ion homeostasis and degeneration events in cardiomyopathy. Furthermore, there appears to be a clear parallelism in calcium redistribution between hypoxic and cardiomyopathic myocardium.

Animals↗
PubMed1987

Cholinergic innervation of hippocampal GAD- and somatostatin-immunoreactive commissural neurons.

This study describes the cholinergic innervation of chemically defined nonpyramidal neurons in the hilar region of the rat hippocampus. Cholinergic terminals were identified by immunocytochemistry employing a monoclonal antibody against choline acetyltransferase (ChAT), the acetylcholine-synthesizing enzyme, and the avidin-biotin-peroxidase (ABC) technique. Nonpyramidal neurons in the hilar region were characterized by immunostaining with antibodies against glutamate decarboxylase (GAD), the gamma aminobutyric acid (GABA)-synthesizing enzyme, and somatostatin (SS). The immunoreactivity to these antibodies was detected by using biotinylated secondary antibodies and avidinated ferritin as an electron-dense marker. This electron microscopic double immunostaining procedure enabled us to demonstrate that immunoperoxidase-labeled ChAT-immunoreactive terminals established symmetric synaptic contacts on the ferritin-labeled GAD- and SS-immunoreactive hilar cells. In additional experiments at least some of the GAD- and SS-immunoreactive hilar neurons were further characterized as commissural neurons by retrograde filling with horseradish peroxidase (HRP) following an injection of the tracer into the contralateral hilus. From these triple labeling experiments, we concluded that at least some GABAergic and somatostatin-containing neurons in the hilar region, which are postsynaptic to cholinergic terminals, project to the contralateral hippocampus. Together with previous studies on the cholinergic innervation of the hippocampus and fascia dentata, our present results thus demonstrate that different types of hippocampal cells, including GABAergic and peptidergic commissural neurons in the hilar region, receive a cholinergic input.

Animals↗
PubMed1987

GABAergic nonpyramidal neurons in intracerebral transplants of the rat hippocampus and fascia dentata: a combined light and electron microscopic immunocytochemical study.

Glutamate decarboxylase (GAD) immunocytochemistry was used to study GABAergic neurons and synapses in intracerebral allografts of the rat hippocampus and fascia dentata. Tissue blocks of regio inferior of Ammon's horn (hippocampal field CA3) or of the fascia dentata were taken from newborn rats and transplanted to the hippocampal region of young adult rats. After 6 1/2 months' survival the recipient brains were fixed by perfusion and serially sectioned on a Vibratome. Sections containing the transplant and/or the host hippocampal region were immunostained for GAD and flat-embedded in Araldite for a correlated light and electron microscopic analysis. Immunostained neurons and terminals in the transplants were compared to immunoreactive elements in the hippocampus and fascia dentata of the hosts and other, normal rats. As in the hippocampal formation in situ, GAD-immunoreactive neurons and terminals in the transplants were observed in all layers. In dentate transplants a preponderance of immunostained cells was found just beneath the granule cell layer. In both hippocampal and dentate transplants, immunoreactive terminals were most abundant in the cell layers where they formed characteristic pericellular baskets around the pyramidal and granule cell bodies. In the electron microscope, the transplant GAD-immunoreactive neurons exhibited numerous cytoplasmic organelles, deeply infolded nuclei, and nuclear rods. Immunoreactive terminals formed symmetric synaptic contacts on the cell bodies, dendritic shafts, and spines of transplant pyramidal cells, granule cells, and hilar neurons. These are normal characteristics of GAD-immunoreactive neurons and terminals as also observed in the hippocampus of the host rats and the normal controls. Our results demonstrate that GABAergic neurons survive transplantation and develop a cell-specific morphology that includes the axonal projections.

Animals↗
PubMed1987

Choline acetyltransferase-immunoreactive neurons and terminals in the rat septal complex: a combined light and electron microscopic study.

A monoclonal antibody against choline acetyltransferase (ChAT), the acetylcholine synthesizing enzyme, was used to determine the morphological characteristics of cholinergic neurons and axon terminals within the rat septum. Light microscopy revealed numerous large fusiform or multipolar ChAT-immunoreactive neurons in the medial septal nucleus/diagonal band complex (MSDB). In contrast, virtually no immunostained cells were found in the lateral septum (Nc. septalis dorsalis and Nc. septalis lateralis). Fine immunostained fibers were most abundant close to the midline in the MSDB mainly following an ascending course. A few thin ChAT-immunoreactive fibers and terminallike pericellular punctate structures were observed in the inner part of the dorsal septal nucleus. Electron microscopy of ChAT-immunoreactive neurons revealed large cell bodies rich in cytoplasmic organelles. The cell nuclei regularly exhibited multiple invaginations of the nuclear membrane. Only rarely were terminals found that established synaptic contacts on the cell bodies of immunostained neurons. In contrast, numerous terminals formed synaptic contacts on immunoreactive dendrites. ChAT-immunopositive terminals were studied in thin sections from the MSDB and from the dorsal septal nucleus. In both regions they appeared as heavily immunostained vesicle-filled boutons that established symmetric and asymmetric synaptic contacts. In the dorsal septal nucleus immunostained terminals often showed a basketlike arrangement around immunonegative cell bodies. Our fine structural study provides evidence that cholinergic neurons in the MSDB are similar to cholinergic neurons in the basal nucleus and neostriatum, which have been described by other investigators. The presence of cholinergic synapses in the septal complex indicates that this region not only contains cholinergic projection neurons, but receives a cholinergic input itself.

Animals↗
PubMed1987

Fine structure of GABAergic neurons and synapses in the human dentate gyrus.

Surgical tissue samples of the human dentate gyrus were immunostained for glutamate decarboxylase (GAD), the gamma-aminobutyric acid (GABA)-synthesizing enzyme, and studied by both light and electron microscopy. Immunoreactive neurons and terminals displayed similar morphological characteristics as known from studies in laboratory animals. Thus, GAD-positive neurons prevailed in the hilar region, whereas immunoreactive terminals were most frequently observed in the granular layer forming symmetric synaptic contacts with dendrites, cell bodies and axon initial segments of granule cells.

Glutamate Decarboxylase↗
PubMed1987

Fine structure and synaptic connections of identified neurons in the rat fascia dentata.

A survey is given of the synaptic connections of identified neurons in the rat fascia dentata based on our own Golgi/electron microscopic and light and electron microscopic immunocytochemical findings as well as on results obtained from the literature. The report largely deals with the dominating cell type in the region, the dentate granule cell. Of the various types of hilar cells, the GABAergic neurons, particularly the inhibitory basket cells, are taken into account. Differences in fine structure between granule cells and basket cells as well as mutual synaptic connections between these two types of dentate neurons are elaborated. This survey may provide a basis for further neurophysiological and pharmacological studies on these cells.

Animals↗
PubMed1987

GABAergic input of cholecystokinin-immunoreactive neurons in the hilar region of the rat hippocampus. An electron microscopic double immunostaining study.

Double immunostaining was performed for electron microscopy to analyze the synaptic connections between glutamate decarboxylase (GAD)-immunoreactive axons and cholecystokinin (CCK)-immunoreactive neurons in the hilar region of the rat hippocampal formation. Following immunostaining for CCK, the diaminobenzidine (DAB) reaction product was silver-intensified and gold-substituted. In a subsequent second immunostaining for GAD, the immunoreactive elements were labeled using a single DAB reaction. Electron microscopic analysis of the double-stained Vibratome sections demonstrated that the single DAB-labeled GAD-immunoreactive boutons form symmetrical synaptic connections on the soma and primary dendrites of the DAB-gold-labeled CCK-immunoreactive neurons.

3,3'-Diaminobenzidine↗
PubMed1986

Synaptic connections of cholecystokinin-immunoreactive neurons and terminals in the rat fascia dentata: a combined light and electron microscopic study.

We report here on the fine structure and synaptic connections of neurons and axon terminals in the rat fascia dentata displaying immunoreactivity to antibodies against cholecystokinin octapeptide (CCK). In the fascia dentata and hilar region, CCK-immunoreactivity was confined to nonpyramidal neurons that were similar in appearance to basket cells known to use gamma-aminobutyric acid (GABA) as neurotransmitter. These neurons exhibited dense accumulations of endoplasmic reticulum and infolded nuclei, and established asymmetric and symmetric synaptic contacts with presynaptic terminals. Among those terminals that formed asymmetric synaptic contacts, giant mossy fiber boutons arising from granule cell axons were identified. Cholecystokinin-immunoreactive terminals established symmetric synaptic contacts on the cell bodies and dendrites of granule cells. Similar contacts were formed on nonimmunoreactive hilar neurons. Some of these hilar cells were identified as commissural neurons by retrograde filling with horseradish peroxidase (HRP) following injection of the tracer into the contralateral fascia dentata. Synaptic contacts were rarely observed between immunolabeled pre- and postsynaptic elements. The results are discussed with regard to inhibitory processes in the fascia dentata since other studies have shown that CCK is coexistent with GABA in hippocampal nonpyramidal neurons.

Animals↗
PubMed1986

Intracerebral transplants of the rat fascia dentata: a Golgi/electron microscope study of dentate granule cells.

In the present study we describe the morphological characteristics of dentate granule cells in intracerebral allografts of the rat fascia dentata. Blocks of hippocampal tissue containing the fascia dentata were taken from late embryonic and newborn rats and transplanted to the hippocampal region of other newborn and young adult rats. After survival periods of several months the recipient brains were fixed by perfusion and serially sectioned on a Vibratome. Some sections were stained with thionin to determine the localization and general histological organization of the transplants, while others were Golgi stained with a modification of the section Golgi technique. Well-impregnated transplant granule cells were gold-toned and deimpregnated thus allowing a correlated, light and electron microscopic analysis of identified neurons to be done. At the light microscopic level the morphology of the dentate granule cells in the transplants was very similar to Golgi-impregnated, gold-toned granule cells in the fascia dentata of normal rats (controls). A few irregular, more obliquely curved dendrites occurred, but basal dendrites passing into the hilar region were never observed. Following an initial spine-free segment granule cell dendrites were densely covered with spines. The axon, the mossy fiber, originated as usual from the basal pole of the cell body. In the electron microscope, both small and larger complex spines (v and w types) were seen to emerge from the gold-toned dendrites of the identified granule cells. The thin unmyelinated granule cell axons gave rise to giant mossy fiber boutons in the dentate hilus, but in addition numerous aberrant mossy fiber terminals were found innermost in the dentate molecular layer just above the granule cell layer. The results demonstrate that dentate granule cells that have gone through the major part of their differentiation after transplantation develop characteristic dendritic and axonal elements very similar to those of granule cells in the fascia dentata in situ. The minor changes observed correspond to the redistribution of intrinsic connections that results from the absence of major extrinsic afferents.

Animals↗
PubMed1986

The cholinergic innervation of the rat fascia dentata: identification of target structures on granule cells by combining choline acetyltransferase immunocytochemistry and Golgi impregnation.

A monoclonal antibody against choline acetyltransferase (ChAT), the acetylcholine-synthesizing enzyme, was used to study cholinergic synapses on identified (Golgi stained) granule cells in the rat fascia dentata. Choline acetyltransferase immunocytochemistry was applied to 40-microns Vibratome sections cut perpendicular to the longitudinal axis of the hippocampus. Light microscopy revealed fine varicose ChAT-immunoreactive axons in all layers of the fascia dentata, i.e., in the stratum moleculare, the stratum granulosum, and the subgranular polymorph zone. Most fibers were observed in the vicinity of granule cell bodies where they ran mainly parallel to the granular layer. Next, the immunostained Vibratome sections were sandwiched between small pieces of Parafilm and piled to form a block that was covered with agar and Golgi stained. After that, the sections were separated by cutting away the agar and removing the Parafilm. Sections containing well-impregnated granule cells were gold-toned (Fairén et al., '77), embedded in Araldite, and subjected to ultrathin sectioning for electron microscopy. A total of 14 gold-toned granule cells were examined in the electron microscope for synaptic contacts with cholinergic afferents. Choline acetyltransferase-immunoreactive axon terminals were observed that established symmetric synaptic contacts with the cell bodies and dendritic shafts of the gold-toned identified granule cells. Two types of contact were observed on spines arising from gold-toned granule cell dendrites. Immunoreactive terminals established asymmetric synaptic contacts with the head of small spines and symmetric contacts with the stalk of large, complex spines. The boutons forming asymmetric synaptic contacts with the cup-shaped spine head of the complex spines were not found to be immunoreactive. Our results demonstrate that cholinergic fibers to the rat fascia dentata establish characteristic types of synaptic contact with different postsynaptic elements of granule cells, suggesting a complex function of this afferent system.

Animals↗
PubMed1986

Cholinergic neurons in the hippocampus. A combined light- and electron-microscopic immunocytochemical study in the rat.

We report here on cholinergic neurons in the rat hippocampal formation that were identified by immunocytochemistry employing a monoclonal antibody against choline acetyltransferase (ChAT), the acetylcholine-synthesizing enzyme. In general, ChAT-immunoreactive cells were rare, but were observed in all layers of the hippocampus proper and fascia dentata with a preponderance in zones adjacent to the hippocampal fissure and in the part of CA1 bordering the subiculum. All immunoreactive cells found were non-pyramidal neurons. They were relatively small with round or ovoid perikarya, which gave rise to thin spine-free dendrites. These hippocampal neurons were very similar to ChAT-immunoreactive cells in the neocortex of the same animals but were quite different from cholinergic neurons in the basal forebrain, medial septal nucleus, and neostriatum, which were larger and more intensely immunostained. Electron-microscopic analysis of ChAT-immunoreactive cells in the hippocampus and fascia dentata revealed synaptic contacts, mainly of the asymmetric type, on cell bodies and smooth proximal dendrites. The nuclei of the immunoreactive cells exhibited deep indentations, which are characteristic for non-pyramidal neurons. Our results provide evidence for an intrinsic source of the hippocampal cholinergic innervation in addition to the well-established septo-hippocampal cholinergic projection.

Animals↗