A model of a human neuromuscular system for small isometric tensions

A model is constructed of the motor units in the human first dorsal interosseus (FDI) muscle. Each motorneuron is simulated using a pseudo-steady-state model that omits the membrane capacity and the events underlying the action potential. Properties of individual twitches in the corresponding muscle units are based on the data of Milner-Brown et al. for the FDI, while the transduction between steady firing rate and percentage of maximum tension in a muscle unit is based on the work of Rack and Westbury on the cat soleus muscle. Since we are concerned only with small isometric tensions, we ignore effects due to muscle spindles and to recurrent inhibition. The model allows one to to determine, by simulation, the tension-time functions produced by different programs of input to an entire pool of 120 motorneurons. Thus, for example, in order to produce tension rising linearly with time, it suffices to deliver to each neuron in the pool a non-linearly rising conductance; the conductance can be the same for all neurons in the pool, but can NOT be scaled in proportion to the surface area of the respective neurons. The input may be delivered to any part of the neuron's dendritic tree, as long as the electrotonic distribution of input is the same for all the neurons. For a linearly rising force produced in this way, most of the motorneurons yield similar slopes for their frequency-force curves, as observed by Milner-Brown et al. To produce tensions greater than about 1 kg, mechanisms not included in this model must come into play, i.e. perhaps introduction of phasic motorneurons. The most important data needed to improve this model are sets of isometric frequency-force curves for muscle units of different twitch tensions.     

The role of cAMP and Ca on the modulation of junctional conductance: an integrated hypothesis

The role of cAMP and Ca in the modulation of junctional permeability is discussed. An integrated hypothesis is presented which proposes that cAMP modulates the junctional conductance through the activation of specific kinases and phosphorylation of gap junction proteins. A close-loop feed-back between cAMP and Ca is assumed to be relevant in the regulation of junctional conductance under physiological conditions. According to this hypothesis hormones modulate the junctional permeability through variations in the intracellular concentration of cAMP. It is known that in several tissues the cells are connected through low resistance intercellular junctions (Loewenstein, 1966; Bennett, 1973; De Mello, 1975, 1932a). Ions and small molecules can flow freely from cell-to-cell across narrow hydrophilic channels (De Mello, 1982a). This type of intercellular coupling is essential for the fast propagation of the impulse and the synchronization of electrical activity in excitable tissues (Bennett, 1973; De Mello, 1982a). It has been proposed that the exchange of chemical signals between cells is important for metabolic cooperation (Gilula et al. 1972) and growth control (Loewenstein, 1979). Therefore, the modulation of junctional conductance is a significant feature of cell biology. Evidence has been provided that the increase in free [Ca2+]i can produce cell decoupling in Chironomus salivary gland (Loewenstein et al., 1967) and in mammalian cardiac fibers (De Mello, 1972, 1975). The free [Ca2+]i required to suppress cell-to-cell coupling is difficult to determine because Ca ions are continuously taken up by mitochondria, sarcoplasmic reticulum or are extruded from the cell. In salivary gland a concentration of free [Ca2+]i of about 5-8 X 10(-5) M was found to be associated with cell decoupling (Loewenstein et al., 1967). The major difficulty here is that the concentration of the ion determined in the bulk of the cytosol is not necessarily the same near the gap junctions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Further studies on the E blood group system in pigs

The blood group system E in pigs is similar to the B system in cattle, one of the most complicated of the hitherto known blood group systems.
Studies of Andresen (1957), Saison (1958), Andresen & Wroblewski (1959), Andresen et al. (1959), Andresen (1962, 1965), Rasmusen (1965), Hojný et al. (1966), Dinklage et al. (1966), Dinklage & Major (1968), Hradecký & Hojný (1972), Hojný & Hradeck (1972, 1973) lead to the determination of the various E alleles.
This report presents information of a new blood group factor E_p in pigs.     

An attempt at comparison of the morphology of normal and RSV--transformed cells in a scanning microscope

The electronic scanning microscope (SEM) was first used to analyze biological material in 1965 (Hollenberg M. et al. The Journal of Histochem. and Cytochem. 21, 109-130, 1973). It has since been possible to collect specific data on cell morphology and the changes in cell surface and structure caused by external factors, such as oncogenic viruses.     

Intrinsic and network rhythmogenesis in a reduced traub model for CA3 neurons

We have developed a two-compartment, eight-variable model of a CA3 pyramidal cell as a reduction of a complex 19-compartment cable model [Traub et al, 1991]. Our reduced model segregates the fast currents for sodium spiking into a proximal, soma-like, compartment and the slower calcium and calcium-mediated currents into a dendrite-like compartment. In each model periodic bursting gives way to repetitive soma spiking as somatic injected current increases. Steady dendritic stimulation can produce periodic bursting of significantly higher frequency (8–20 Hz) than can steady somatic input (<8 Hz). Bursting in our model occurs only for an intermediate range of electronic coupling conductance. It depends on the segregation of channel types and on the coupling current that flows back-and-forth between compartments. When the soma and dendrite are tightly coupled electrically, our model reduces to a single compartment and does not burst. Network simulations with our model using excitatory AMPA and NMDA synapses (without inhibition) give results similar to those obtained with the complex cable model [Traub et al, 1991; Traub et al, 1992]. Brief stimulation of a single cell in a resting network produces multiple synchronized population bursts, with fast AMPA synapses providing the dominant synchronizing mechanism. The number of bursts increases with the level of maximal NMDA conductance. For high enough maximal NMDA conductance synchronized bursting repeats indefinitely. We find that two factors can cause the cells to desynchronize when AMPA synapses are blocked: heterogeneity of properties amongst cells and intrinsically chaotic burst dynamics. But even when cells are identical, they may synchronize only approximately rather than exactly. Since our model has a limited number of parameters and variables, we have studied its cellular and network dynamics computationally with relative ease and over wide parameter ranges. Thereby, we identify some qualitative features that parallel or are distinguished from those of other neuronal systems; e.g., we discuss how bursting here differs from that in some classical models.     

Giemsa banding patterns in chronic lymphocytic leukaemia.

The banding patterns of chromosomes from 20 patients with chronic lymphocytic leukaemia (C.L.L.) have been analyzed. 97 of 100 metaphases examined had a normal banding pattern. The 3 remaining metaphases, all from one patient had bands similar to those seen after aging. It is concluded that the chromosomes in C.L.L. have normal banding patterns. The majority of cytogenetic studies in chronic lymphocytic leukaemia have reported normal chromosomes (Fitzgerald and Adams 1965; Oppenheim et al., 1965; Lawler et al., 1968). An inherited abnormality of G group chromosome (No. 22) has been reported in a family, three members of whom developed C.L.L. (Fitzgerald and Hamer, 1969), but further investigations of cases of familial leukaemia failed to reveal a similar abnormality (Fitzgerald et. al., 1966). The development of new techniques which allow the positive identification of individual chromosomes (Caspersson et al., 1969; Dutrillaux and Lejeune, 1971; Sumner et al., 1971; Seabright, 1971), has revolutionised human cutogenetics and revealed additional information regarding chromosome abnormalities and leukaemia (Rowley, 1973; Lobb et al., 1972; Milligan and Garson, 1974). The purpose of this investigation was to determine whether the chromosomes in C.L.L. have normal banding patterns.     

Pollen Tubes: a Model System for Plant Cell Growth*

Recent observations of pollen tubes show that these tubes may grow in a pulsatory fashion (Pierson et al., 1995; Plyushch et al., 1995; Li et al., 1996; Geitmann et al., 1996a, 1996b), in which phases of fast and slow growth alternate regularly. The occurrence of pulsatory growth has been used by Geitmann and coworkers (1996b) to study factors that might control growth. Their results emphasize the role of the cell wall and secretory events in regulating pollen tube growth. Here we will briefly review recent results related to the role of exocytosis, cytoskeleton, calcium and the cell wall in pollen tube growth.     

States of high conductance in a large-scale model of the visual cortex

This paper reports on the consequences of large, activity dependent, synaptic conductances for neurons in a large-scale neuronal network model of the input layer 4C of the Macaque primary visual cortex (Area V1). This high conductance state accounts for experimental observations about orientation selectivity, dynamics, and response magnitude (D. McLaughlin et al. (2000) Proc. Natl. Acad. Sci. USA 97: 8087–8092), and the linear dependence of Simple cells on visual stimuli (J. Wielaard et al. (2001) J. Neuroscience 21: 5203–5211). The source of large conductances in the model can be traced to inhibitory corticocortical synapses, and the model's predictions of large conductance changes are consistent with recent intracellular measurements (L. Borg-Graham et al. (1998) Nature 393: 369–373; J. Hirsch et al. (1998) J. Neuroscience 15: 9517–9528; J.S. Anderson et al. (2000) J. Neurophysiol. 84: 909–926). During visual stimulation, these conductances are large enough that their associated time-scales become the shortest in the model cortex, even below that of synaptic interactions. One consequence of this activity driven separation of time-scales is that a neuron responds very quickly to temporal changes in its synaptic drive, with its intracellular membrane potential tracking closely an effective reversal potential composed of the instantaneous synaptic inputs. From the effective potential and large synaptic conductance, the spiking activity of a cell can be expressed in an interesting and simplified manner, with the result suggesting how accurate and smoothly graded responses are achieved in the model network. Further, since neurons in this high-conductance state respond quickly, they are also good candidates as coincidence detectors and burst transmitters.     

A model for steady isometric muscle activation

The present model of the motoneuronal (MN) pool – muscle complex (MNPMC) is deterministic and designed for steady isometric muscle activation. Time-dependent quantities are treated as time-averages. The character of the model is continuous in the sense that the motor unit (MU) population is described by a continuous density function. In contrast to most already published models, the wiring (synaptic weight) between the input fibers to the MNPMC and the MNs (about which no detailed data are known) is deduced, whereas the input–force relation is given. As suggested by experimental data, this relation is assumed to be linear during MU recruitment, but the model allows other, nonlinear relations. The input to the MN pool is defined as the number of action potentials per second in all input fibers, and the excitatory postsynaptic potential (EPSP) conductance in MNs evoked by the input is assumed to be proportional to the input. A single compartment model with a homogeneous membrane is used for a MN. The MNs start firing after passing a constant voltage threshold. The synaptic current–frequency relation is described by a linear function and the frequency–force transformation of a MU by an exponential function. The sum of the MU contraction forces is the muscle force, and the activation of the MUs obeys the size principle. The model parameters were determined a priori, i.e., the model was not used for their estimation. The analysis of the model reveals special features of the activation curve which we define as the relation between the input normalized by the threshold input of the MN pool and the force normalized by the maximal muscle force. This curve for any muscle turned out to be completely determined by the activation factor, the slope of the linear part of the activation curve (during MU recruitment). This factor determines quantitatively the relation between MU recruitment and rate modulation. This property of the model (the only known model with this property) allows a quantification of the recruitment gain (Kernell and Hultborn 1990). The interest of the activation factor is illustrated using two human muscles, namely the first dorsal interosseus muscle, a small muscle with a relatively small force at the end of recruitment, and the medial gastrocnemius muscle, a strong muscle with a relatively large force at the end of recruitment. It is concluded that the present model allows us to reproduce the main features of muscle activation in the steady state. Its analytical character facilitates a deeper understanding of these features. Received: 24 November 1997 / Accepted in revised form: 30 November 1998     

A model of the electrophysiological properties of nucleus reticularis thalami neurons.

A model of the electrophysiological properties of rodent nucleus reticularis thalami (NRT) neurons of the dorsal lateral thalamus was developed using Hodgkin-Huxley style equations. The model incorporated voltage-dependent rate constants and kinetics obtained from recent voltage-clamp experiments in vitro. The intrinsic electroresponsivity of the model cell was found to be similar to several empirical observations. Three distinct modes of oscillatory activity were identified: 1) a pattern of slow rhythmic burst firing (0.5-7 Hz) usually associated with membrane potentials negative to approximately -70 mV which resulted from the interplay of ITs and IK(Ca); 2) at membrane potentials from approximately -69 to -62 mV, rhythmic burst firing in the spindle frequency range (7-12 Hz) developed and was immediately followed by a tonic tail of single spike firing after several bursts. The initial bursting rhythm resulted from the interaction of ITs and IK(Ca), with a slow after-depolarization due to ICAN which mediated the later tonic firing; 3) with further depolarization of the membrane potential positive to approximately -61 mV, sustained tonic firing appeared in the 10-200-Hz frequency range depending on the amplitude of the injected current. The frequency of this firing was also dependent on the maximum conductance of the leak current, IK(leak), and an interaction between the fast currents involved in generating action potentials, INa(fast) and IK(DR), and the persistent Na+ current, INa(P). Transitions between different firing modes were identified and studied parametrically.     

Repetitive firing of Renshaw spinal interneurons

A model of the Renshaw spinal interneuron has been developed. The model consists of a nonhomogeneous cylinder divided into three compartments: dendrites, soma and axon initial segment (I.S). The soma and dendrites are represented as a cylindrical cable by the method of Rall (1962); anatomical data of Jankowska and Lindström (1971) from fluorescent dye injections were used to construct the cable. The soma and I.S. membranes are assumed to have Hodgkin-Huxley-like membrane activity. In comparison with our previous model of a tonic motorneuron (Traub, 1977), the Renshaw cell has a faster membrane time constant, faster Hodgkin-Huxley rate functions, _h and _h shifted to the right on the voltage axis, and no slow potassium conductance. With appropriate input conductances, the Renshaw cell model exhibits the following features: it develops very high frequency bursts (over 1000 impulses per s) which trail off over a period of 10–20 ms; the second spike has small amplitude and successive spikes develop progressively larger amplitudes. Comparisons are drawn with the experimental observations of Eccles et al. (1961) and Willis and Willis (`966). With this model, it is feasible to compute the steady firing rate for a large number of steady synaptic excitatory and inhibitory conductances by direct integration of the differential equations.     

A study and model of the role of the Renshaw cell in regulating the transient firing rate of the motoneuron

 This study sought to investigate the role of the Renshaw cell with respect to transient motoneuron firing. By studying the cat motoneuron and Renshaw cell, several low-order lumped parameter models were developed that simulate the known characteristics of the injected input current vs. firing rate. The neuron models in the Renshaw cell inhibition configuration were tuned to fit experimental data from cat motoneurons. Models included both linear versions and those with sigmoidal nonlinearities. Results of the simulation indicate that the motoneuron itself provides the adaptation seen in its firing rate and that the Renshaw cell’s role is primarily to fine-tune the motoneuron’s adaptation process. Received: 23 July 1993/Accepted in revised form: 9 February 1994     

Production of presumptive humoral haematopoietic regulators in canine cyclic haematopoiesis

Abstract. Conditioned media (CM) were prepared according to previously published techniques from the bone marrow of dogs with cyclic haematopoiesis (CH). CM prepared from day 9 marrows inhibited mouse bone marrow CFU-s proliferation rate while CM from day 10 marrows were stimulatory and also contained an erythroid stimulating factor which appeared to be erythropoietin. In addition a highly significant trend from CM containing CFU-s inhibitory materials to media with CFU-s stimulatory activity was observed through cycles day 1 to 8. These studies further support the concept that CH is due to a defect in factors controlling stem cell proliferation and suggest that a major event occurs in CH dog marrow on days 9 and/or 10 of the cycle. Bone marrow transplantation studies (Dale & Graw, 1974; Weiden et al., 1974; Jones et al., 1975b) have indicated that canine cyclic haematopoiesis (CH) is probably due to a disorder in the multipotential stem cells. Morphological evidence (Scott et al., 1973) and the almost synchronous cycling of CFU-e, CFU-c and diffusion chamber progenitor cells (DCPC) (DUM et al., 1977, 1978a, b) lend support to such a theory. However, efforts to identify the mechanisms controlliig multipotential stem cell proliferation in dogs have been handicapped by the lack of suitable techniques to study these cells in the canine. Recently, Wright and co-workers (Wright & Lord, 1978, 1979; Wright et al., 1979; Lord et al., 1979), on the basis of previous observations (Frindel et al., 1976; Frindel & Guigon, 1977), described the preparation of species non-specific, bone marrow conditioned media (CM) which are capable of influencing the proliferation rate of murine colony forming units-spleen (CFU-s). The studies now reported were designed to determine if CM prepared from canine CH marrow would influence the proliferation rate of murine bone marrow CFU-s. The results indicate that a major event, possibly related to the in vivo control of stem cell proliferation in dogs with CH, occurs on days 9–10 of the cycle; day 1 being the first day when the peripheral blood neutrophil count falls below-1600 mm³.     

Endogenous burst capability in a neuron of the gastric mill pattern generator of the spiny lobster Panulirus interruptus

The gastric system of the lobster stomatogastric ganglion has previously been thought to include no neurons capable of endogenous bursting. We describe conditions under which one of the motorneurons, the CP cell, can burst endogenously in a free-running manner in the absence of other phasic network activity. Isolated preparations of the foregut nervous system were used, and the CP bursting was either spontaneous or was activated by continuous stimulation of an input nerve. Three criteria were applied to establish the endogenous nature of such burst generation in CP: absence of phasic input, reset of the bursting pattern by pulses of current in a characteristic phase-dependent manner, and modulation of burst rate by sustained injected current. (1) The firing of other cells which are known to be related synaptically to CP was monitored in nerve records. These other cells were either silent or fired only tonically. Cross-correlograms showed that CP bursting was not ascribable to phasic activity in these other network cells. (2) A depolarizing current pulse of sufficient strength injected intracellularly between bursts triggered a burst prematurely and reset the subsequent rhythm. A hyperpolarizing pulse during a burst terminated it and reset the subsequent rhythm. Reset behavior was similar to that described for other endogenous bursters. (3) Application of a positive-going ramp current initially caused an increase in burst rate, as described for other endogenous bursters. However, further depolarization caused a slower burst rate due to lengthening of the individual bursts, although mean firing frequency continued to increase throughout the range tested. Such free-running endogenous repetitive bursting appeared to result from the CP's ability to produce slow regenerative depolarizations (“plateau potentials”). When bursting was present, so was the plateau property, as determined by I–V analysis and by the ability of brief current pulses to trigger and terminate bursts. The previous inability to observe endogenous bursting in preparations with central input removed may be due to the usual absence of the plateau property in such preparations.     

The role of a transient potassium current in a bursting neuron model

Presented here is a biophysical cell model which can exhibit low-frequency repetitive activity and bursting behavior. The model is developed from previous models (Av-Ron et al. 1991, 1993) for excitability, oscillations and bursting. A stepwise development of the present model shows the contribution of a transient potassium current (I _A ) to the overall dynamics. By changing a limited set of model parameters one can describe different firing patterns; oscillations with frequencies ranging from 2–200 Hz and a wide range of bursting behaviors in terms of the durations of bursting and quiescence, peak firing frequency and rate of change of the firing frequency.     

The characteristic three-banded birefringence of ligamentum nuchae elastic fibres indicates ordered micellar texture

The ultrastructural organization of the elastic fibres of bovine ligamentum nuchae is still controversial (Kádár 1979; Sandberg 1976; Sandberg et al. 1981; Quintarelli et al. 1973; Gosline 1976). Polarization microscopy demonstrated convincingly, contrary to a recent negative report (Aaron and Gosline 1980), an ordered birefringent micellar texture (Schmidt 1939; Romhányi 1965; Fischer 1979). The three-banded anisotropic pattern of the fibres can be explained by the optical interference of two micellar textures of opposite orientation, one arranged circularly in the surface layer and the other oriented longitudinally in the axial core of the fibres (Romhányi 1965). Analysis of the underlying molecular mechanism for the anisotropic staining reaction of these fibres with Congo red led to the conclusion that this is due to a definite structural order of specific cross-linking segments within the random network of elastin. The anisotropic staining reaction of the elastic fibres with Congo red is described as the most simple method to demonstrate the three-banded birefringent pattern of ligamentum nuchae elastic fibres even in histologic sections.     

Independence of the unimodal tuning of firing rate from theta phase precession in hippocampal place cells

There are two prominent features for place cells in rat hippocampus. The firing rate remarkably increases when rat enters the cell’s place field and reaches a maximum around the center of place field, and it decreases when the animal approaches the end of the place field. Simultaneously the spikes gradually and monotonically advance to earlier phase relative to hippocampal theta rhythm as the rat traverses along the cell’s place field, known as temporal coding. In this paper, we investigate whether two main characteristics of place cell firing are independent or not by mainly focusing on the generation mechanism of the unimodal tuning of firing rate by using a reduced CA1 two-compartment neuron model. Based on recent evidences, we hypothesize that the coupling of dendritic with the somatic compartment is not constant but dynamically regulated as the animal moves further along the place field, in contrast to previous two-compartment modeling. Simulations show that the regulable coupling is critically responsible for the generation of unimodal firing rate profile in place cells, independent of phase precession. Predictions of our model accord well with recent observations like occurrence of phase precession with very low as well as high firing rate (Huxter et al. Nature 425:828–832, 2003) and persistency of phase precession after transient silence of hippocampus activity (Zugaro et al. Nat Neurosci 8:67–71, 2005.     

Noise-induced divisive gain control in neuron models

A recent computational study of gain control via shunting inhibition has shown that the slope of the frequency-versus-input (f-I) characteristic of a neuron can be decreased by increasing the noise associated with the inhibitory input (Neural Comput. 13, 227-248). This novel noise-induced divisive gain control relies on the concommittant increase of the noise variance with the mean of the total inhibitory conductance. Here we investigate this effect using different neuronal models. The effect is shown to occur in the standard leaky integrate-and-fire (LIF) model with additive Gaussian white noise, and in the LIF with multiplicative noise acting on the inhibitory conductance. The noisy scaling of input currents is also shown to occur in the one-dimensional theta-neuron model, which has firing dynamics, as well as a large scale compartmental model of a pyramidal cell in the electrosensory lateral line lobe of a weakly electric fish. In this latter case, both the inhibition and the excitatory input have Poisson statistics; noise-induced divisive inhibition is thus seen in f-I curves for which the noise increases along with the input I. We discuss how the variation of the noise intensity along with inputs is constrained by the physiological context and the class of model used, and further provide a comparison of the divisive effect across models.