Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: a hypothesis for the etiology of schizophrenia

A tumor mass removed from the subcutaneous tissue of the shoulder of a dog had the light and electron microscopic features of extraneuraxial meningioma. The neoplasm probably arose from arachnoid cap cells displaced during embryogenesis. Although intracranial canine meningiomas are common ( 141 no primary menin- gioma, to our knowledge, has been reported outside the central nervous system in dogs or other animal species. Extraneuraxial meningiomas occur occasionally in man and are predominantly in the head and neck area (13). We are aware of only one such neoplasm in man in which the meningiomatous nature of the lesion was confirmed by electron microscopy (13). There is no similar ultrastructural study in the veterinary literature.

http://link.springer.com/content/pdf/10.1007%2FBF00685277.pdf

A Light and Electron Microscopic Study

We describe the design and operation of a machine that freezes biological tissues by contact with a cold metal block, which incorporates a timing circuit that stimulates frog neuromuscular junctions in the last few milliseconds before thay are frozen. We show freeze-fracture replicas of nerve terminals frozen during transmitter discharge, which display synpatic vesicles caught in the act of exocytosis. We use 4-aminopyridine (4-AP) to increase the number of transmitter quanta discharged with each nerve impulse, and show that the number of exocytotic vesicles caught by quick-freezing increases commensurately, indicating that one vesicle undergoes exocytosis for each quantum that is discharged. We perform statistical analyses on the spatial distribution of synaptic vesicle discharge sites along the "active zones" that mark the secretory regions of these nerves, and show that individual vesicles fuse with the plasma membrane independent of one another, as expected from physiological demonstrations that quanta are discharged independently. Thus, the utility of quick-freezing as a technique to capture biological processes as evanescent as synaptic transmission has been established. An appendix describes a new capacitance method to measure freezing rates, which shows that the "temporal resolution" of our quick-freezing technique is 2 ms or better.

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Synaptic vesicle exocytosis captured by quick freezing and correlated with quantal transmitter release.

Publisher Summary Intercellular junctions are specialized regions of contact between the apposed plasma membranes of adjacent cells, and recent evidence suggests that they are essential for the development of multicellular organisms. They provide the structural means for groups of cells to interact in certain defined ways, and thereby enable them to create structures of higher order. This chapter reviews the morphological information on intercellular junctions derived from thin-sectioning, negative staining and freeze-cleave techniques, as well as from x-ray diffraction and biochemical investigations, and correlates the structural parameters with known or proposed physiological functions. The membrane structure of intercellular junctions is described. Membrane proteins can be divided into two groups: peripheral and integral. Peripheral membrane proteins are believed to be associated with the membrane surface, based on the observation that they are held to the membrane by rather weak noncovalent interactions, and are not strongly associated with membrane lipids. Only mild treatments, such as an increase in ionic strength of the medium or the addition of a chelating agent, are needed to dissociate them molecularly intact from the membrane. Furthermore, in the dissociated state they are relatively soluble in neutral aqueous buffers. In contrast, integral membrane proteins appear much more strongly bound to the lipid matrix, since they can be dissociated from the latter only by drastic treatments with chemicals such as detergents, protein denaturants, and organic solvents. The diversity in structure and function of intercellular junctions offers an exciting field for future research in which morphologists, physiologists, and biochemists should be able to make significant contributions to the knowledge of how individual cells interact to form structures of higher order.

Structure and function of intercellular junctions.

▪ Abstract Olfaction begins with the transduction of the information carried by odor molecules into electrical signals in sensory neurons. The activation of different subsets of sensory neurons to different degrees is the basis for neural encoding and further processing of the odor information by higher centers in the olfactory pathway. Recent evidence has converged on a set of transduction mechanisms, involving G-protein-coupled second-messenger systems, and neural processing mechanisms, involving modules called glomeruli, that appear to be adapted for the requirements of different species. The evidence is highlighted in this review by focusing on studies in selected vertebrates and in insects and crustaceans among invertebrates. The findings support the hypothesis that olfactory transduction and neural processing in the peripheral olfactory pathway involve basic mechanisms that are universal across most species in most phyla.

Mechanisms of olfactory discrimination : Converging evidence for common principles across phyla

Ultrastructure of the "active zone" in the frog neuromuscular junction.

An electron-microscopic study of zinc iodide-osmium impregnation of neurons. I. Staining of synaptic vesicles at cholinergic junctions

Electron micrographs of presynaptic membrane faces were obtained from replicas of aldehyde-fixed, freeze-fractured neuropil of mammalian and avian C.N.S. There is strong evidence that the presynaptic membrane is split and that the exposed membrane faces represent the inner and outer membrane leaflet respectively. Presynaptic sites on the inner face appear as patches adhering to postsynaptic elements and include a distinctly indented area. They bear clusters of membrane particles and a varying number of small protuberances. The latter apparently occur in presynaptic membranes exclusively and form hexagonal patterns corresponding to the ‘presynaptic vesicular grid’. Evidence is presented that the protuberances are temporary attachment sites of transmitter vesicles to the presynaptic membrane. These contacts may be identical with the sites of transmitter release.

The fine structure of freeze-fractured presynaptic membranes

Contribution to the problem of structural organization of the presynaptic area

Vitrification of biological specimens in liquid nitrogen can be achieved under high pressure (2,100 bars). This procedure obviates the use of aldehyde fixation and cryoprotection (glycerol). The present work demonstrates its applicability to the freeze-etching of mammalian brain tissue. Freeze-fracture replicas from rat cerebellar cortex and subfornical organ prepared by this method are compared to conventionally processed material using aldehyde fixation, glycerination and freezing with Freon. The formation of large ice crystals is prevented in tissue blocks up to 0.5 mm thick; deep etching is markedly enhanced. Cytoplasmic microstructures such as mitochondrial cristae, microtubules and microfilaments, are readily observable against a finely granulated cytosol matrix. An additional advantage is the combined application with freeze-substitution.

Clara Sandri

Papers

Ultrastructure of the "active zone" in the frog neuromuscular junction.

An electron-microscopic study of zinc iodide-osmium impregnation of neurons. I. Staining of synaptic vesicles at cholinergic junctions

The fine structure of freeze-fractured presynaptic membranes

Contribution to the problem of structural organization of the presynaptic area

The influence of high pressure freezing on mammalian nerve tissue