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Biomedical subjects

F S Sjöstrand

Publications and source records attributed to F S Sjöstrand.

At least 19 recordsLinked to original sources
PubMed2005

Concepts, facts and artifacts in electron microscopy.

This communication illustrates how the electron microscope has contributed to biochemistry by revealing how multienzyme systems in mitochondria are structurally organized to secure high speed ATP synthesis and has extended physiology to the molecular level. Ribonucleoprotein complexes form a gel in the cytoplasm determining the conditions for translation... Photoreceptor stimulation involves two phases, trapping of light by a light reflecting cylinder formed by the outer segment disks and energy transduction by bleaching of photopigment molecules changing the charge of the outer segment disks driving the photoreceptor toward hyperpolarization. Revealing the synaptic connections between retinal neurons extends neurophysiology to the level of information processing by neural circuits, which are designed for high speed processing. Spatial brightness contrast enhancement is eliminated in connection with macular degeneration, which leads to partial blindness, revealing the importance of contrast enhancement for vision.

Adenosine Diphosphate↗
PubMed2004

Movement perception, directionally selective ganglion cell responses and the involuntary eye movements. Neurophysiology at the level of information processing.

Two neural circuits in the retina are described, that involve neural interaction generated by image movement. One circuit increases the sensitivity in detecting movement in the visual field while the other circuit generates ganglion cell signals when an image moves in one preferred direction but not when moves in the opposite direction, explaining the observation of directionally selective ganglion cell responses described by Barlow and Hill (1963). In agreement with the recorded potentials, the circuit generates ganglion cell responses also when the light stimulus is stationary. This ambiguity in ganglion cell signals to the visual center limits the signals usefulness to images that are in constant movement. The only known such movement is that caused by the involuntary eye movements. The function of the circuit is therefore to stabilize the retinal image when transmitted to the visual center.

Animals↗
PubMed2003

Color vision at low light intensity, dark adaptation, Purkinje shift, critical flicker frequency and the deterioration of vision at low illumination. Neurophysiology at the nanometer range of neural structure.

The discovery that color vision extends to low illumination reported in this communication eliminates the duplicity theory as an explanation of vision differing at high and low illumination. Instead, an explanation of the difference was found when analyzing synaptic interaction between retinal neurons, made possible by revealing the synaptic connections between the neurons through three-dimensional reconstruction of the outer plexiform layer and by applying information communicated by published recordings of the potential of retinal neurons. The synaptic connections revealed the existence of a large horizontal cell network and of cone networks. The networks contribute continuous information regarding average light intensity over an area of the retina. The opposite sign of the network input maintains bipolar cell threshold constant when illumination varies. When at low illumination the network potential approaches a minimum the consequent extensive increase of transmitter release at network synapses eliminates fine tuning of synaptic transmission at these synapses. This accounts for the deterioration of vision at low illumination by eliminating spatial brightness contrast enhancement and also accounts for the difference in critical flicker frequency at high and low illumination. Network interference accounts for the two phases of dark adaptation and for the Purkinje shift. The analysis revealed conditions for particularly fast synaptic transmission leading to cascade like transmission at sequences of synapses. The overall design of the neural circuits establishes conditions for fast processing of information. This is the consequence of the neurons responding with graded changes of the membrane potential and conducting potentials electrotonically. Such neurons are therefore particularly suitable for processing of information.

Animals↗
PubMed2003

Kuffler's inhibitory surround, the function of the inner plexiform layer and an information processing unit in the retina. Neural interaction at the nanometer level.

Comparing Kuffler's recordings of ganglion cell discharges and bipolar cell responses to the same stimuli, deduced on the basis of a knowledge of synaptic connections between the neurons, revealed that the bipolar cell signals had not been modified by synaptic interaction in the inner plexiform layer. This layer therefore receives bipolar cell signals generated by groups of bipolar cells within the center of ganglion cell receptive fields, sorts and distributes the signals to a (compared to the number of photoreceptors and bipolar cells), small number of ganglion cells in such a way that the retinal image can be reconstructed in the visual center by reversing the fusion. Transmission between photoreceptor and bipolar cell is controlled by an information processing circuit receiving information from one photoreceptor, from the large horizontal cell network, formed by synaptic connections between the large horizontal cell processes, from cone networks formed by the cone processes connecting cones and from one small horizontal cell. Interaction between input neurons shapes the input to the bipolar cell. The interaction establishes a gate like control of transmission at the bipolar cell synapse and maintains bipolar cell threshold at a constant level, two features that prevent noise in the output signal. The output is generated by simultaneous input from all input neurons at the bipolar cell synapse, a multiinput synapse. Bipolar cell response is therefore based on perfect timing of fusion of information and of the neural interaction preceding fusion. Proper timing is secured by the dimensions of the components of the circuit measuring in the nanometer range. The volume of the information processing circuit is only 0.3 cubic micrometer, which is less than one two hundredth the volume of the soma of a bipolar cell. Extension of the study of the nervous system to the nanometer level opens a new field of research by making it possible to analyze how information contributed by the sense organs is processed in the nervous system to regulate body functions.

Animals↗
PubMed2002

Sequential pictorial presentation of neural interaction in the retina. 2. The depolarizing and hyperpolarizing bipolar cells at rod terminals.

Each rod is connected to one depolarizing and one hyperpolarizing bipolar cell. The synaptic connections of cone processes to each bipolar cell and presynaptically to the two rod-bipolar cell synapses establishes conditions for lateral interaction at this level. Thus, the cones raise the threshold for bipolar cell depolarization which is the basis for spatial brightness contrast enhancement and consequently for high visual acuity (Sjöstrand, 2001a). The cones facilitate ganglion cell depolarization by the bipolar cells and cone input prevents horizontal cell blocking of depolarization of the depolarizing bipolar cell, extending rod vision to low illumination. The combination of reduced cone input and transient hyperpolarization of the hyperpolarizing bipolar cell at onset of a light stimulus facilitates ganglion cell depolarization extensively at onset of the stimulus while no corresponding enhancement applies to the ganglion cell response at cessation of the stimulus, possibly establishing conditions for discrimination between on- vs. off-signals in the visual centre. Reduced cone input and hyperpolarization of the hyperpolarizing bipolar cell at onset of a light stimulus accounts for Granit's (1941) 'preexcitatory inhibition'. Presynaptic inhibition maintains transmitter concentration low in the synaptic gap at rod-bipolar cell and bipolar cell-ganglion cell synapses, securing proportional and amplified postsynaptic responses at these synapses. Perfect timing of variations in facilitatory and inhibitory input to the ganglion cell confines the duration of ganglion cell depolarization at onset and at cessation of a light stimulus to that of a single synaptic transmission.

Amacrine Cells↗
PubMed2001

Sequential pictorial presentation of neural interaction in the retina. 1. The synaptic ribbon complex.

The analysis of circuits in the retina revealed by three-dimensional reconstructions (Sjöstrand, 1958, 1974, 1976,1978, 1990) is presented in a simplified way by series of schematic drawings illustrating each individual step in the sequence of synaptic transmission between the neurones. In addition, the analysis has been extended further compared to earlier presentation (Sjöstrand, 1998a). The circuit of the synaptic ribbon complex controls transmission between cones and bipolar cells by the inhibitory input from horizontal cells being controlled by the cone. At low light intensity, horizontal cell inhibition blocks transmission between cones and bipolar cells because of high concentration of transmitter at the critical synapse, explaining fading of cone vision. The requirement for maintaining a low transmitter concentration at the synapses to secure proportionality between input and output signals is established by horizontal cell inhibitory input both at the cone-bipolar cell and the cone-horizontal cell synapses. How one bipolar cell can transmit information regarding average light intensity over a large area of the retina is discussed in detail.

Animals↗
PubMed1999

Molecular pathology of Luft disease and structure and function of mitochondria.

Luft disease, studied in detail by Luft et al. (1962) is characterized clinically by hypermetabolism and consequent abnormal transpiration. In their study, Luft and coworkers revealed that the hypermetabolism is caused by extensive uncoupling of mitochondrial respiration in skeletal muscle tissue. They also discovered that the muscle mitochondria had been structurally modified with the cristae assuming a zig-zag conformation. The mitochondrial enzymes functioned normally, the abnormality being confined to the extensive uncoupling of respiration. In an earlier study (Sjöstrand et al., 1988) it was revealed that the zig-zag conformation is caused by removal of some tricarboxylic acid cycle enzymes from the cristae, exposing the interior of the cristae to the matrix fluid. Applying a coupling theory proposed by Sjöstrand (1990, 1991), leakage of protons from the cristae should impair coupling of respiration and ATP synthesis. The structural damage is conceived of to be caused by a genetic defect preventing proper aggregation of the enzyme molecules in the cristae. Luft disease may therefore be the first known disease caused primarily by a structural disorder at the molecular level. The symptoms of the disease reveal the importance of the compact and ordered aggregation of the enzyme molecules in the cristae for coupling of respiration.

Adenosine Triphosphate↗
PubMed1998

Structure determines function of the retina, a neural center. 1. The synaptic ribbon complex.

A new approach to study the function of the retina is described. It involves a precise revealing of synaptic connections between the neurons by means of three-dimensional volume reconstructions. Identification of several hundreds of synapses revealed the existence of groups of synaptically interconnected neurons constituting discrete neural circuits accounting for processing of information contributed by the photoreceptors. Supplementary information contributed by electrophysiological recordings of membrane potentials of neurons in these circuits made it possible to determine how information is processed by the circuits. Two versions of one of the circuits are analyzed in this communication.

Animals↗
PubMed1998

Structure determines function of the retina, a neural center. 2. The second, third and fourth circuits.

Three retinal circuits are analyzed on the bases of established circuit diagrams. The synaptic interaction at one circuit involves depolarizing bipolar cells connected to rods and shows the important contribution to function of the connections between cones and rods including connections of cones to bipolar cells connected to rods. Another circuit explains that one type of bipolar cell is depolarized at cessation of the stimulus. Because each photoreceptor is connected to both on- and off- bipolar cells, on- and off- responses are generated from each photoreceptor. The cone connections to rods and to bipolar cells connected to rods extend rod vision to low ambient illumination while the absence of corresponding connections at cone terminals leads to cone vision being blocked at low ambient illumination. The cone connections raise the threshold for stimulation of bipolar cells connected to rods and lower temporal resolution of rod vision relative to cone vision. The timing of interaction between bipolar cells, amacrine cells and ganglion cells in the inner plexiform layer makes inhibitory and facilitatory modulation of ganglion cell potential establish optimal conditions for ganglion cell activation. The agreement between bipolar cell responses determined on the basis of the analysis of the circuit diagrams and the responses recorded from bipolar cells shows that the function of a neural center such as the retina can be analyzed on the basis of circuit diagrams.

Models, Biological↗
PubMed1998

Structure determines function of the retina, a neural center. 3. Contrast enhancement, directional selectivity, some incomplete circuits.

In Part 3 a circuit for spatial brightness contrast enhancement is analyzed as well as a circuit for generation of directionally selective bipolar cell responses. Several types of bipolar cells with a special function contribute to the complexity of the circuitry of the outer plexiform layer, indicating that the analysis presented in this review only represents the tip of the iceberg.

Animals↗
PubMed1998

Structure determines function of the retina, a neural center. 4. The 'duplex' nature of vision.

Part 4 reveals how the differences in the quality of vision at high and low illumination are explained by synaptic interaction between the neurons in the outer plexiform layer changing with illumination. Analysis of data available in the literature revealed that rod vision is active over the entire range of light intensities generating visual responses. It is revealed that the input from the retina to brain centers involves information regarding a black and white image based on rod vision, which is improved with respect to spatial brightness contrast and darkness contrast by cone interference. Cones add color to the image, further increasing image contrast. The duplicity theory is shown to be based on erratic assumptions regarding how rods and cones function. The theory lacks an experimental basis and is not required to explain differences in the quality of the perceived images at high and low illumination.

Animals↗
PubMed1997

The physical chemical basis for preserving cell structure for electron microscopy at the molecular level and available preparatory methods.

A method to prepare tissues for electron microscopy based on the kinetic theory of physical chemistry makes it possible to study the structure of cells at the molecular level because extensive denaturation of proteins is avoided in contrast to using conventional preparatory methods. The highly ordered arrangement of mitochondrial enzymes revealed by applying this method is discussed. Low temperature embedding, freeze-substitution, freeze-drying combined with low temperature embedding and freeze-fracturing are evaluated with respect to conditions for protein denaturation.

Animals↗
PubMed1992

Information and misinformation regarding ischemia of heart muscle tissue. The cause of cell death during blood reperfusion and reactivation of heart muscle tissue after prolonged ischemia.

An electron microscopic study of heart muscle tissue exposed to six hours ischemia and prepared according to the low denaturation embedding technique revealed a structural modification confined to the mitochondrial cristae. The modification consisted of a removal of Krebs cycle enzymes from the cristae. Reperfusion of the ischemic tissue after four hours ischemia led to extensive breakdown of the mitochondrial structure and contractility could not be restored. However, when after six hours ischemia the ischemic tissue was reperfused with blood, the composition of which had been modified to stimulate mitochondrial function, no additional structural changes were observed and contractility was restored. The structural damage caused by reperfusion with non modified blood is explained by a loss of control of plasma membrane permeability caused by impaired ATP production which makes the ionic composition of the cytosol approach that of blood plasma, stopping oxidative phosphorylation. A treatment to restore heart muscle function after long periods of ischemia and after heart transplantation is proposed. The structural damage revealed that the Krebs cycle and the respiratory chain enzymes are associated according to a regular periodic pattern and that the enzyme molecules are closely aggregated three-dimensionally. Earlier electron microscopic studies revealing massive structural deterioration of heart muscle cells already after 45 to 60 minutes ischemia leading to the conclusion that the cells are irreversibly damaged, is based on fixation artifacts caused by osmium fixation. This study has been carried out in collaboration with the research team of Gerald D. Buckberg at the Thoracic Surgery Division at University of California at Los Angeles.

Animals↗
PubMed1991

Molecular structure of mitochondrial cristae, solid state biochemistry and a simple theory of respiration-phosphorylation coupling.

Thanks to the improvement of preparatory procedures in electron microscopy during the 1960's the structural analysis of mitochondria has been extended to the molecular level leading to an almost 40-year-old misconception regarding mitochondrial structure being replaced by a more realistic version of the structure. The following observations are reviewed: 1) There are three different types of membranes in the mitochondria. 2) Geometrically regularly distributed circumscribed respiratory chain domains are surrounded by a continuous tricarboxylic acid cycle domain. 3) The cristae are compact structure with the enzyme molecules in a three-dimensional arrangement. 4) The active sites of most enzyme molecules are buried in the cristae and are exposed to an environment characterized as a biological solid state. 5) A water translocating mechanism removes water from the cristae maintaining a low water activity in the cristae. 6) The cristae are connected to the cytosol directly through proteinaceous pathways extending through the two surface membranes. 7) The matrix communicates with the cytosol by a route through the two surface membranes, bypassing the cristae. 8) The permeability of the inner surface membrane changes with the respiratory state. 9) The inner membrane particles can be made to appear under experimental conditions that prove their appearance to be an artifact. 10) A simple theory of respiration-phosphorylation coupling is proposed based on the solid state of the cristae. The theory agrees with the chemiosmotic theory with respect to the involvement of proton movement as basis for energy transduction, but differs with respect to how protons contribute to transduction.

Animals↗
PubMed1990

The mitochondrial inner surface membrane and its connections.

Using conservative methods to isolate heart muscle mitochondria fractions and to break open the mitochondria resulted in the release of large fragments of the inner surface membrane. After negative staining these fragments were characterized structurally by the presence of particles with a uniform size and a mean diameter of 110 A, distributed uniformly in the membrane with the exception of 400 A wide circumscribed areas within which these particles were missing and instead larger particles were closely associated. These areas are the sites at which the stalklike connections extending from the cristae are inserted at the inner surface membrane, whereby the cristae are connected to the proteinaceous pathways that according to Sjöstrand and Candipan (1985) pass through the two surface membranes establishing a connection between the cristae and the cytosol.

Animals↗
PubMed1989

An elementary information processing component in the circuitry of the retina generating the on-responses.

A pattern of neural connections that is a compulsory feature of photoreceptor terminals and is referred to as the synaptic ribbon complex was analyzed, and by combination of the structural information and information gained by intracellular recordings from photoreceptors, horizontal cells, and bipolar cells, it is possible to explain how the hyperpolarizing effect of light stimulating the photoreceptors is changed to a depolarization of depolarizing bipolar cells. The sign reversal is accomplished by the hyperpolarizing action of the horizontal cells on the photoreceptors, which blocks the transmission between the photoreceptors and the bipolar cells. This blocking action is controlled by the photoreceptor and it functions like a gate that is opened only when the photoreceptor is stimulated by light. The synaptic ribbon complex offers an example of an elementary information processing component with three input channels to the bipolar cells with each channel contributing a different piece of information and with the processing occurring presynaptically. Additional processing of information occurs within the dendritic tree through interactions of the responses of the individual dendritic endings to different types of input. This interaction can involve partial blocking of the conduction within the dendritic tree, making the interaction considerably more complex than simple summation. The responses recorded intracellularly from neurons reveal only the end result of the processing of information at the level of that neuron.

Animals↗
PubMed1989

A mechanism for spatial brightness contrast enhancement and a basis for the duplicity of vision.

Cones are connected to bipolar cells connected to rods by processes extending laterally from the cone terminals (Sjöstrand, 1958). The cone connections have been studied further in the rabbit retina. Structurally these connections are typical synaptic connections. It can be deduced that these connections must affect the onresponses of bipolar cells connected to rods in such a way that spatial brightness contrast is enhanced. The connections raise the threshold for rod vision and slow down the changes in the membrane potential of on-bipolar cells. These effects offer an explanation for the duplicity of vision.

Animals↗