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S L Palay

Publications and source records attributed to S L Palay.

At least 37 records · Page 2Linked to original sources
PubMed1979

Gamma-aminobutyric acid pathways in the cerebellum studied by retrograde and anterograde transport of glutamic acid decarboxylase antibody after in vivo injections.

Injections of characterized antibody against glutamic acid decarboxylase (GAD), the enzyme responsible for the synthesis of gamma-aminobutyric acid (GABA), were made into the cerebellum. Small cortical injections of anti-GAD antibody produced labeled stellate, basket, Purkinje, and Golgi cells and their processes at the injection site. Anterograde transport of GAD antigen-antibody complexes in Purkinje cell axons caused intense labelling of terminals in deep cerebellar and several vestibular nuclei. Small groups of mossy fiber rosettes labeled and produced retrograde labeling and GAD immunoreactivity in a small number of pleomorphic neurons in the deep cerebellar nuclei. Injections into the dentate nucleus produced retrograde labeling in Purkinje cell bodies and anterograde label in a small number of mossy fiber rosettes. All projections conformed to previously reported topographic distributions of corticonuclear and nucleocortical cerebellar pathways. These findings confirm the GABA content of most Purkinje cell-deep nuclei connections and provide new evidence for a GABA component in part of the nucleocortical pathway in the cerebellum. Immunocytochemical controls for specificity were conducted by injections of preimmune rabbit serum as a substitute for GAD antibody. Only nonspecific labeling was obtained in these cases. Colchicine caused a cumulative enhancement of GAD immunoreactivity in all cases. The present studies indicate that the method of in vivo antibody injections can be utilized to study chemically specific connections in nervous tissue.

Animals↗
PubMed1979

Immunocytochemical localization of cyclic GMP: light and electron microscope evidence for involvement of neuroglia.

Guanosine 3',5'-cyclic monophosphate (cGMP) immunoreactivity in the rat's cerebellum was studied with light and electron microscopy by the indirect fluorescence method and the peroxidase-antiperoxidase method. Labeled cells included neuroglial cells in the cerebellar cortex, white matter, and deep nuclei; some stellate and basket cells in the cortex; and some large neurons in the deep nuclei. No evidence was found for sagittal microzonation in the cGMP distribution. In the labeled cells, cGMP immunoreactive sites were localized to surface membranes, organelles, and the cytoplasmic matrix. Specificity was indicated by the same pattern of labeling after treatment with cGMP immunoglobulin that had been adsorbed with adenosine 3',5'-cyclic monophosphate (cAMP) and by the failure to label after treatment with normal rabbit sera or with cGMP immunoglobulin that had been adsorbed with 1 mM cGMP. Cerebella treated with cAMP antisera, however, showed immunoreactivity in Purkinje cells, granule cells, and Golgi cells in addition to neuroglia in cortex and deep nuclei. Sequential norepinephrine and glutamate superfusions generally intensified cGMP immunoreactivity, not only in neuroglial cells but also in the background. Under these conditions some Purkinje cells and some granule cells were also labeled. Increased cGMP immunoreactivity was also obtained by treatment with harmaline, gamma-aminobutyric acid and aminooxyacetic acid, muscimol, gamma-aminobutyric acid, or apomorphine in order of decreasing effectiveness. Serotonin and colchicine produced no detectable increase of cGMP immunoreactivity above normal, and diazepam and sodium pentobarbital decreased it. In these experiments, diethyl ether was preferable to sodium pentobarbital for anesthesia on account of the depressive action of the latter on cGMP immunoreactivity. Thus, drugs that increase cerebellar activity enhance cGMP levels, whereas those that decrease cerebellar activity decrease cGMP levels. However, it is not clear whether these fluctuations in cGMP levels are a direct consequence of neurotransmitter function or are sequelae to other related events. The present study suggests that some neurons and many neuroglial cells are the major sites of cGMP in the cerebellum.

Animals↗
PubMed1979

Immunocytochemical localization of gamma-aminobutyric acid transaminase at cellular and ultrastructural levels.

gamma-Aminobutyric acid transaminase (GABA-Tase; 4-aminobutyrate:2-oxaglutarate aminotransferase, EC 2.6.1.19) immunoreactivity in the rat's cerebellum was studied by light and electron microscopy with indirect immunofluorescence and peroxidase-antiperoxidase methods. Evidence is presented for neuronal and neuroglial compartments of GABA-Tase. Labeled neurons included stellate, basket, Purkinje, and Golgi cells of the cortex and a few large neurons in the deep nuclei. Labeled neuroglia included those surrounding Purkinje cells, their radial fibers in the molecular layer, and astrocytes in the granular layer and deep nuclei. No evidence for sagittal microzonation was found. At the ultrastructural level, GABA-Tase immunoreactive sites were localized to cell surface membranes, intracellular organelles, and the cytoplasmic matrix. GABA-Tase immunoreactivity at synapses could be localized precisely to pre- and postsynaptic membranes in gamma-aminobutyric acid (GABA)-containing as well as non-GABA-containing neurons. Specific label was absent from tissues treated with normal rabbit preimmune sera. GABA-Tase labeling was more intense in tissues from animals anesthetized with ether than with barbiturates and after formaldehyde fixation without glutaraldehyde. Increased GABA-Tase immunoreactivity was observed on treatment with colchicine, GABA with oxamic acid, GABA, harmaline, norepinephrine and glutamate, or diazepam (in order of decreasing effectiveness). Serotonin produced no detectable change, and apomorphine and muscimol decreased the immunoreactivity.

4-Aminobutyrate Transaminase↗
PubMed1978

Serotonin and substance P coexist i, neurons of the rat's central nervous system.

5-Hydroxytryptamine (serotonin)-containing neurons in the rat's medullary raphe and interfascicularis hypoglossi cell groups were identified by means of autoradiography following prolonged intraventricular administration of 5-hydroxy[(3)H]tryptamine, fluorescence histochemistry for the demonstration of endogenous 5-hydroxytryptamine, and microspectrofluorimetric analysis of excitation and emission spectra. Immunocytochemical methods (the unlabeled primary antibody-peroxidase antiperoxidase and indirect immunofluorescence methods) were applied with antisera to substance P in order to localize immunoreactivity in these medullary neurons. It was demonstrated that the raphe nuclei and the interfascicularis hypoglossi nucleus are heterogeneous cell groups that contain: (i) Neurons that display both an uptake-storage capacity for 5-hydroxy[(3)H]tryptamine and a formaldehyde-induced fluorescence with spectral characteristics identical to those of the 5-hydroxytryptamine fluorophor. These cells exhibit high to low fluorescence intensities without detectable substance P-like immunoreactivity. (ii) Neurons with various 5-hydroxytryptamine fluorescence intensities and intense to low degrees of substance P-like immunoreactivity. (iii) Neurons with various degrees of substance P-like immunoreactivity without detectable 5-hydroxytryptamine fluorescence or 5-hydroxy[(3)H]tryptamine uptake and storage capacity. These results indicate that some neurons contain high or low levels of only 5-hydroxytryptamine or substance P, whereas other neurons contain both 5-hydroxytryptamine and substance P in various proportions. The present findings demonstrate the presence of two putative transmitters, a biogenic amine and a polypeptide, within the same neuron in the mammalian central nervous system.

Animals↗
PubMed1978

Ultrastructural localization of gamma-aminobutyric acid receptors in the mammalian central nervous system by means of [3H]muscimol binding.

This study utilizes tritiated muscimol binding and electron microscope autoradiography (Ilford L4 emulsion and phenidone development) to localize gamma-aminobutyric acid (GABA) receptor sites in the cerebellum of the rat. In the cerebellar cortex, silver grains were associated with somata and dendrites of basket and stellate cells in the molecular layer, with somata and primary and secondary dendritic shafts of Purkinje cells, axons and terminals of basket cells in the pinceau or basket, initial axonal segments and myelinated axons of Purkinje cells, and dendrites of granule and Golgi cells in the granular layer, and with somata and dendritic shafts of large and small cells in the cerebellar nuclei. These data correspond well to the light-microscope-autoradiographic observations in the cerebellum previously reported [Chan-Palay, V. (1978) Proc. Natl. Acad. Sci. 75, 1024-1028]. Label over GABA receptor sites can be localized to the plasma membranes between pre- and postsynaptic elements at synaptic junctions, of which 88.9% of the samples are axodendritic and the remaining 11.1% are axosomatic. GABA receptor sites are also found along axonal membranes of the GABA-containing basket cell within the basket surrounding Purkinje cells, where true axo-axonal synapses are rare. It is speculated that GABA receptors in the basket may suggest a possibility of the basis for synchronization, either self-inhibition or facilitation within the basket formation, or presynaptic suppression of inhibitory action of basket cell on Purkinje cell.

Aminobutyrates↗
PubMed1977

Immunocytochemical identification of substance P cells and their processes in rat sensory ganglia and their terminals in the spinal cord: light microscopic studies.

The indirect immunofluorescence method and the unlabeled primary antibody peroxidase antiperoxidase method are used to demonstrate the substance P (SP) plexus in the spinal cord and SP cells in the sensory ganglia of the rat. The normal untreated and the control side of the dorsal rhizotomized rat show vast SP immunoreactive plexuses in the substantia gelatinosa, central gray, and ventral gray regions of the spinal cord. In each sensory ganglion, approximately 250 SP immunoreactive cells are found singly or in small groups of 2 or 3, near blood capillaries or among ganglion and satellite cells. They contain intensely immunoreactive cytoplasmic granules 0.1-3.0 mum across. Occasionally, free intensely immunoreactive granules are found in the surrounding tissue near an SP cell but not clearly within the confines of the cell. Another type of immunoreaction has been observed with both methods. A less intense, homogeneous reactivity has been found in lamellae insinuated between ganglion cells and near blood capillaries close to an SP cell; the characteristic disposition of this homogeneous reactivity suggests an extracellular location. Unilateral rhizotomy results in an increased number of immunoreactive SP cells and nerve fibers as well as a more extensive homogeneous immunoreactivity. These results add to existing evidence that SP cells in sensory ganglia send fibers via the dorsal roots to the spinal cord. SP cells, fibers, and terminals do not take up exogenously applied (125)I-labeled [Tyr(8)]SP and cannot be demonstrated by subsequent autoradiography. No neurotensin immunoreactive cells were found in sensory ganglia.

Animals↗
PubMed1977

Ultrastructural identification of substance P cells and their processes in rat sensory ganglia and their terminals in the spinal cord by immunocytochemistry.

The unlabeled substance P (SP) antibody-peroxidase-antiperoxidase reaction was used on tissue prior to embedding in epoxy reins for ultrastructural identification of the SP cell and its immunoreactive granules. The SP cell is 10-20 mum in diameter and has sparse cytoplasm with numerous intensely reactive SP granules 100-300 nm across, large clear vacuoles, elaborate smooth endoplasmic reticulum, fragmentary rough endoplasmic reticulum, dispersed ribosomes, few mitochondria, and a modest Glogi apparatus. The large SP-reactive granules are discharged into the extracellular space, either with cell membrane intact or as unbound dense material. The membrane-bound dense granucles are transported intact through endothelial cells into the blood or are picked up by Schwann cells and fibroblasts. Other SP-reactive granules lose their limiting membranes, fragment, and then disperse into fine immunoreactive grains that bind to the extracellular matrix and to collagen. Dispersed SP-reactive granules are transported within myriad pinocytotic vesicles across endothelial cells with numerous luminal plications and are discharged into the blood. Pinocytosis of dispersed SP-reactive material, that can be detected intracellularly, also occurs in Schwann cells and fibroblasts. The SP axons to the substantia gleatinosa are unmyelinated or finely myelinated. Their synaptic varicosities display a generalized axoplasmic immunoreactivity, which also occurs in and around small vesicles. The larger SP synaptic vesicles are intensely reactive.

Animals↗
PubMed1976

A guide to the synaptic analysis of the neuropil.

A morphological analysis of the organization of the gray matter in the central nervous system depends on the discovery of consistent repetitive patterns. Without these, the gray matter remains a chaotic jungle. An hypothesis derived from the study of a few simple regions has been developed to serve as a guide in finding these patterns. It states that all nerve fibers and terminals arising from a particular group of nerve cells, or, more precisely, a particular nerve cell type, display similar axoplasmic configurations despite variations in size and shape of the terminations. This hypothesis is reminiscent of the so-called Dale's principle that a nerve cell makes use of the same transmitter at all of its branches or terminations. These apparent rules of uniformity or congruity merely reflect the functional integrity of the nerve cell and the role of its parts in the nervous system. But as an hypothesis, it needs to be tested, and it needs to be tested anew in each region, since exceptions to the assumed rule can be expected. It is therefore proposed as the first working hypothesis in each new region. If it should prove to be true in general, it will facilitate and rationalize the analysis of the gray matter, as it has already done in the cerebellar cortex and the deep cerebellar nuclei. If it should prove to be false in a few regions, the analysis will become more difficult, and additional modes of marking nerve endings will have to be used. Experimental methods for identifying nerve terminals can be translated from the light microscopic to the electron microscopic level, but there are significant drawbacks at both levels: lack of precision, destruction of fibers of passage, and rapid evolution of the degenerative process may greatly restrict their usefulness. Labeling with tritiated amino acids or transmitters, or with horseradish peroxidase, provide new methods for tracing interneuronal connections at the electron microscopic level. These have the advantages of high specificity, nondestructiveness and a physiological mode of selective marking. However, they do not offer a solution to the problem of short-range connections. For these, careful reconstructions of serial sections may prove necessary, as Sjöstrand (1974) has demonstrated in a remarkable paper on the retina. The aim of all these methods is to discover patterns of synaptic connectivity in order to map the cellular organization of the nervous system. In the foregoing, nothing was said about synapses other than those articulating axons with somata or dendrites and their appendages. Clearly the same principles of recognition apply to axo-axonal and dendro-dendritic synapses. Although the synapses that have been considered here are chemical synapses, the same questions regarding the identity of the partners in electrotonic junctions must be asked as well.

Amino Acids↗
PubMed1975

Cytoplasmic inclusions of neurons in the monkey visual cortex (area 19).

Several unusual neuronal inclusions were found in certain cells of the rhesus monkey visual cortex (Area 19): 1. Filamentous bodies, present in the small stellate cells of layer IV, globoid, 0.3-0.6 mum in diameter, consisting of fine 50 A filaments in a hexagonal meshwork. These are often associated with the labyrinthine bodies. 2. Labyrinthine bodies found exclusively in the small stellate cells of layer IV, including certain neurons with dispersed ribosomes. These are 0.4-0.7 mum in diameter and consist of 900 A wide tubes which interconnect with one another. The walls of these tubes are continuous and made up of a sheet or honeycomb lacework of small hexagonal 150 A subunits. 3. This inclusion, an aggregate 0.3-0.7 mum in size, consists of small membrane-bounded vesicles with a single dense granule associated with other non-membrane bound small dense droplets. The inclusions are always associated with the maturing face of the Golgi complex of certain layer IV pyramidal cells; as such, they may be an unusual product of the Golgi apparatus. These observations were confirmed by examination of stereo pairs of electron micrographs. Speculations are made with regard to possible functions for these inclusions.

Animals↗
PubMed1974

A review of lamination in area 17 of the visual cortex Macaca mulatta.

This paper develops a concordance of methods for designating laminae in the primate striate cortex. The classic notation schemes of Ramón y Cajal, Brodmann, and von Bonin and four recent modifications are described in words and photomicrographs. The recent trend toward adopting a lamination scheme that effects a division of cells into recognizable layers and at the same time reflects their connections is considered. Since a single, consistent plan for lamination of the visual cortex would facilitate communication among investigators, it is suggested that Brodmann's original scheme be followed as the most generally useful and applicable.

Animals↗
PubMed1974

Meynert cells in the primate visual cortex.

The solitary cells of Meynert are distinguished by their specific location in layer V of the striate cortex, very large size, argyrophilia, and the profusion of neurofilaments in their dendrites and perikarya. They occur with greater frequency in the macular region of the cortex, spaced a minimal distance of 110 mum apart, at a maximum density of about 8000/cm-2. In the perifoveal cortex, Meynert cells are spaced about 400 mum apart and packed at a density of approximately 625/cm-2. Each Meynert cell has an apical dendrite and many large basal dendrites. The perikaryon and primary segments of all dendrites are spine-free; however, more distally a total of 36 000 spines are present, differentially disposed upon the dendritic surfaces. The basal dendrites bear over 77% of the spines on the Meynert cell, although they account for only 66% of the total length of the dendritic arborization. The first part of the apical dendrite is the most densely decorated with appendages, accounting for almost 10% of the spines on the whole dendritic tree. The apical dendrite becomes progressively less spiny as it passes through the superficial part of layers IV and III; less than 2.5% of the total number of spines of the Meynert cell project from this part of the apical dendrite. When the dendrite reaches layer II it bursts into an umbel of rapidly tapering branches. These are highly spinose, accounting for 8-13% of the cell's total, dispersed over only 23% of the linear dendritic length. It is suggested that this differential distribution of thorns can be correlated with the axonal inputs in the various cortical layers, and that the Meynert cell is designed to receive maximal information from layers I and II, and from layers V and VI, which are sources mainly of intracortical inputs. Thus the Meynert cell may be principally concerned with integrative information. In the perifoveal cortex, the basal dendrites of adjacent Meynert cells overlap considerably, and the apical terminal bouquet dendrites do not. In the macular cortex, because of the increased frequency of these neurons, both basaal and apical terminal dendritic fields overlap. A model is developed to illustrate these hypotheses.

Animals↗
PubMed1974

Neuronal perikarya with dispersed, single ribosomes in the visual cortex of Macaca mulatta.

Numerous small and medium-sized neuronal perikarya in layers III and IV of the visual cortex display an unusual pattern of ribosomal distribution. Instead of being aggregated in clusters, spirals, rows, and other regular polysomal configurations, the ribosomes, whether free or attached to the endoplasmic reticulum, are randomly dispersed, with no discernible pattern. The endoplasmic reticulum in such cells is reduced to a few (perhaps only one) meandering, broad cisternae, which delimit broad fields of cytoplasmic matrix occupied almost solely by scattered, single ribosomes. The Golgi apparatus is elaborate. Mitochondria are either small and numerous or large and infrequent. The other organelles, including the nucleus and nucleolus, are not remarkable. Axonal terminals synapse in the normal fashion on the surfaces of these cells and their dendrites. Associated with these cells are more numerous intermediate cells in which a few to many polysomal clusters can be found. It is proposed that the neurons with dispersed, single ribosomes are inactive in protein synthesis and that the suspension of such an important metabolic activity is probably temporary. Thus, these cells are considered to be part of a population undergoing cyclic fluctuations in the intensity of protein synthesis that should be correlated with their specific neural behavior.

Animals↗