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R Bertram

Publications and source records attributed to R Bertram.

At least 19 recordsLinked to original sources
PubMed2002

Calcium-activated K+ channels of mouse beta-cells are controlled by both store and cytoplasmic Ca2+: experimental and theoretical studies.

A novel calcium-dependent potassium current (K(slow)) that slowly activates in response to a simulated islet burst was identified recently in mouse pancreatic beta-cells (Göpel, S.O., T. Kanno, S. Barg, L. Eliasson, J. Galvanovskis, E. Renström, and P. Rorsman. 1999. J. Gen. Physiol. 114:759-769). K(slow) activation may help terminate the cyclic bursts of Ca(2+)-dependent action potentials that drive Ca(2+) influx and insulin secretion in beta-cells. Here, we report that when [Ca(2+)](i) handling was disrupted by blocking Ca(2+) uptake into the ER with two separate agents reported to block the sarco/endoplasmic calcium ATPase (SERCA), thapsigargin (1-5 microM) or insulin (200 nM), K(slow) was transiently potentiated and then inhibited. K(slow) amplitude could also be inhibited by increasing extracellular glucose concentration from 5 to 10 mM. The biphasic modulation of K(slow) by SERCA blockers could not be explained by a minimal mathematical model in which [Ca(2+)](i) is divided between two compartments, the cytosol and the ER, and K(slow) activation mirrors changes in cytosolic calcium induced by the burst protocol. However, the experimental findings were reproduced by a model in which K(slow) activation is mediated by a localized pool of [Ca(2+)] in a subspace located between the ER and the plasma membrane. In this model, the subspace [Ca(2+)] follows changes in cytosolic [Ca(2+)] but with a gradient that reflects Ca(2+) efflux from the ER. Slow modulation of this gradient as the ER empties and fills may enhance the role of K(slow) and [Ca(2+)] handling in influencing beta-cell electrical activity and insulin secretion.

Action Potentials↗
PubMed2001

Differential filtering of two presynaptic depression mechanisms.

The filtering of input signals carried out at synapses is key to the information processing performed by networks of neurons. Two forms of presynaptic depression, vesicle depletion and G-protein inhibition of Ca2+ channels, can play important roles in the presynaptic processing of information. Using computational models, we demonstrate that these two forms of depression filter information in very different ways. G-protein inhibition acts as a high-pass filter, preferentially transmitting high-frequency input signals to the postsynaptic cell, while vesicle depletion acts as a low-pass filter. We examine how these forms of depression separately and together affect the steady-state postsynaptic responses to trains of stimuli over a range of frequencies. Finally, we demonstrate how differential filtering permits the multiplexing of information within a single impulse train.

Calcium Channels↗
PubMed2000

Affixal homonymy triggers full-form storage, even with inflected words, even in a morphologically rich language.

This paper investigates whether affixal homonymy, the phenomenon that one affix form serves two or more semantic/syntactic functions, affects lexical processing of inflected words in a similar way for a morphologically rich language such as Finnish as for morphologically restricted languages such as Dutch and English. For the latter two languages, there is evidence that affixal homonymy triggers full-form storage for inflected words (Bertram, R., Schreuder, R., and Baayen, R. H. (in press). The balance of storage and computation in morphological processing: the role of word formation type, affixal homonymy, and productivity. Journal of Experimental Psychology: Learning, Memory, and Cognition; Sereno and Jongman (1997). Processing of English inflectional morphology. Memory and Cognition, 25, 425-437). Two visual lexical decision experiments show the same pattern for Finnish. Apparently, the substantially richer morphology in Finnish does not prevent full-form storage for inflected words when the affix is homonymic.

Cognition↗
PubMed2000

Atomic refinement using orientational restraints from solid-state NMR.

We describe a procedure for using orientational restraints from solid-state NMR in the atomic refinement of molecular structures. Minimization of an energy function can be performed through either (or both) least-squares minimization or molecular dynamics employing simulated annealing. The energy, or penalty, function consists of terms penalizing deviation from "ideal" parameters such as covalent bond lengths and terms penalizing deviation from orientational data. Thus, the refinement strives to produce a good fit to orientational data while maintaining good stereochemistry. The software is in the form of a module for the popular refinement package CNS and is several orders of magnitude faster than previous software for refinement with orientational data. The short computer time required for refinement removes one of the difficulties in protein structure determination with solid-state NMR.

Gramicidin↗
PubMed2000

The phantom burster model for pancreatic beta-cells.

Pancreatic beta-cells exhibit bursting oscillations with a wide range of periods. Whereas periods in isolated cells are generally either a few seconds or a few minutes, in intact islets of Langerhans they are intermediate (10-60 s). We develop a mathematical model for beta-cell electrical activity capable of generating this wide range of bursting oscillations. Unlike previous models, bursting is driven by the interaction of two slow processes, one with a relatively small time constant (1-5 s) and the other with a much larger time constant (1-2 min). Bursting on the intermediate time scale is generated without need for a slow process having an intermediate time constant, hence phantom bursting. The model suggests that isolated cells exhibiting a fast pattern may nonetheless possess slower processes that can be brought out by injecting suitable exogenous currents. Guided by this, we devise an experimental protocol using the dynamic clamp technique that reliably elicits islet-like, medium period oscillations from isolated cells. Finally, we show that strong electrical coupling between a fast burster and a slow burster can produce synchronized medium bursting, suggesting that islets may be composed of cells that are intrinsically either fast or slow, with few or none that are intrinsically medium.

Animals↗
PubMed2000

The role of morphological constituents in reading Finnish compound words.

The processing of transparent Finnish compound words was investigated in 2 experiments in which eye movements were recorded while sentences were read silently. The frequency of the second constituent had a large influence (95 ms) on gaze duration on the target words, but its influence was relatively late in processing: A clear effect only occurred on the probability of a third fixation. The frequency of the whole compound word had a similar influence on gaze duration (82 ms) and influenced eye movements at least as rapidly as did the frequency of the second constituent. These results, together with an earlier finding that the frequency of the first constituent affected the first fixation duration, indicate that the identification of these compound words involves parallel processing of both morphological constituents and whole-word representations.

Adult↗
PubMed2000

The balance of storage and computation in morphological processing: the role of word formation type, affixal homonymy, and productivity.

This article is concerned with the way in which the balance of storage-storing and processing words through full-form representations-and computation-storing and processing words through morpheme-based representations-in lexical processing in the visual modality is affected by the following 3 factors: word formation type (roughly, inflection vs. derivation), productivity, and affixal homonymy. Experimental results for 5 different Dutch suffixes, combined with previous results obtained for 4 comparable Finnish suffixes (R. Bertram, M. Laine, & K. Karvinen, 1999) and 2 Dutch suffixes (R. H. Baayen, T. Dijkstra, & R. Schreuder, 1997), show that none of these factors in isolation is a reliable cross-linguistic predictor of the balance of storage and computation. The authors offer a general framework that outlines how morphological processing is influenced by the interaction of word formation type, productivity, and affixal homonymy.

Adult↗
PubMed2000

The role of derivational morphology in vocabulary acquisition: get by with a little help from my morpheme friends.

This study explores the role of morphology in vocabulary knowledge of 3rd and 6th grade Finnish elementary school children. In a word definition task, children from both grades performed overall better on derived words than on monomorphemic words. However, the results were modified by the factors Frequency and Productivity. Most strikingly, performance on monomorphemic words was disproportionately weaker than on derived words at the low frequency range. At the high-frequency range, derived words with low-productive suffixes yielded poorest performance. We partly make an appeal to the lexical-statistical properties of the Finnish language to explain the interaction of Frequency and Word Structure. At any rate, the results suggest that Finnish elementary school children benefit significantly from utilizing morphology in determining word meanings.

Analysis of Variance↗
PubMed2000

Dynamical complexity and temporal plasticity in pancreatic beta-cells.

We discuss some of the biological and mathematical issues involved in understanding and modelling the bursting electrical activity in pancreatic beta-cells. These issues include single-cell versus islet behaviour, parameter heterogeneity, channel noise, the effects of hormones, neurotransmitters, and ions, and multiple slow biophysical processes. Some of the key experimental and modelling studies are described, and some of the major open questions are discussed.

Acetylcholine↗
PubMed1999

Modeling study of the effects of overlapping Ca2+ microdomains on neurotransmitter release.

Although single-channel Ca2+ microdomains are capable of gating neurotransmitter release in some instances, it is likely that in many cases the microdomains from several open channels overlap to activate vesicle fusion. We describe a mathematical model in which transmitter release is gated by single or overlapping Ca2+ microdomains produced by the opening of nearby Ca2+ channels. This model accounts for the presence of a mobile Ca2+ buffer, provided either that the buffer is unsaturable or that it is saturated near an open channel with Ca2+ binding kinetics that are rapid relative to Ca2+ diffusion. We show that the release time course is unaffected by the location of the channels (at least for distances up to 50 nm), but paired-pulse facilitation is greater when the channels are farther from the release sites. We then develop formulas relating the fractional release following selective or random channel blockage to the cooperative relationship between release and the presynaptic Ca2+ current. These formulas are used with the transmitter release model to study the dependence of this form of cooperativity, which we call Ca2+ current cooperativity, on mobile buffers and on the local geometry of Ca2+ channels. We find that Ca2+ current cooperativity increases with the number of channels per release site, but is considerably less than the number of channels, the theoretical upper bound. In the presence of a saturating mobile buffer the Ca2+ current cooperativity is greater, and it increases more rapidly with the number of channels. Finally, Ca2+ current cooperativity is an increasing function of channel distance, particularly in the presence of saturating mobile buffer.

Calcium↗
PubMed1998

Glucose diffusion in pancreatic islets of Langerhans.

We investigate the time required for glucose to diffuse through an isolated pancreatic islet of Langerhans and reach an equilibrium. This question is relevant in the context of in vitro electrophysiological studies of the response of an islet to step changes in the bath glucose concentration. Islet cells are electrically coupled by gap junctions, so nonuniformities in islet glucose concentration may be reflected in the activity of cells on the islet periphery, where electrical recordings are made. Using a mathematical model of hindered glucose diffusion, we investigate the effects of the islet porosity and the permeability of a surrounding layer of acinar cells. A major factor in the determination of the equilibrium time is the transport of glucose into islet beta-cells, which removes glucose from the interstitial spaces where diffusion occurs. This transport is incorporated by using a model of the GLUT-2 glucose transporter. We find that several minutes are required for the islet to equilibrate to a 10 mM change in bath glucose, a typical protocol in islet experiments. It is therefore likely that in electrophysiological islet experiments the glucose distribution is nonuniform for several minutes after a step change in bath glucose. The delay in glucose penetration to the inner portions of the islet may be a major contributing factor to the 1-2-min delay in islet electrical activity typically observed after bath application of a stimulatory concentration of glucose.

Animals↗
PubMed1997

A simple model of transmitter release and facilitation.

We describe a model of synaptic transmitter release and presynaptic facilitation that is based on activation of release sites by single Ca2+ microdomains. Facilitation is due to Ca2+ that remains bound to release sites between impulses. This model is inherently stochastic, but deterministic equations can be derived for the mean release. The number of equations required to describe the mean release is small, so it is practical to use the model with models of neuronal electrical activity to investigate the effects of different input spike patterns on presynaptic facilitation. We use it in conjunction with a model of dopamine-secreting neurons of the basal ganglia to demonstrate that transmitter release is greater when the neuron bursts than when it spikes continuously, due to the greater facilitation generated by the bursting impulse pattern. Finally, a minimal form of the model is described that is coupled to simple models of postsynaptic receptors and passive membrane to compute the postsynaptic voltage response to a train of presynaptic stimuli. This form of the model is appropriate for neural network simulations.

Basal Ganglia↗
PubMed1997

Evidence that calcium release-activated current mediates the biphasic electrical activity of mouse pancreatic beta-cells.

The electrical response of pancreatic beta-cells to step increases in glucose concentration is biphasic, consisting of a prolonged depolarization with action potentials (Phase 1) followed by membrane potential oscillations known as bursts. We have proposed that the Phase 1 response results from the combined depolarizing influences of potassium channel closure and an inward, nonselective cation current (ICRAN) that activates as intracellular calcium stores empty during exposure to basal glucose (Bertram et al., 1995). The stores refill during Phase 1, deactivating ICRAN and allowing steady-state bursting to commence. We support this hypothesis with additional simulations and experimental results indicating that Phase 1 duration is sensitive to the filling state of intracellular calcium stores. First, the duration of the Phase 1 transient increases with duration of prior exposure to basal (2.8 mM) glucose, reflecting the increased time required to fill calcium stores that have been emptying for longer periods. Second, Phase 1 duration is reduced when islets are exposed to elevated K+ to refill calcium stores in the presence of basal glucose. Third, when extracellular calcium is removed during the basal glucose exposure to reduce calcium influx into the stores, Phase 1 duration increases. Finally, no Phase 1 is observed following hyperpolarization of the beta-cell membrane with diazoxide in the continued presence of 11 mm glucose, a condition in which intracellular calcium stores remain full. Application of carbachol to empty calcium stores during basal glucose exposure did not increase Phase 1 duration as the model predicts. Despite this discrepancy, the good agreement between most of the experimental results and the model predictions provides evidence that a calcium release-activated current mediates the Phase 1 electrical response of the pancreatic beta-cell.

Animals↗
PubMed1997

Transarticular joint reconstruction and indirect plate osteosynthesis for complex distal supracondylar femoral fractures.

In a prospective study conducted between 1992 and 1995, displaced Müller type C2-C3 intraarticular fractures of the distal femur were treated using an indirect plate fixation technique and a lateral parapatellar arthrotomy for the direct reduction of the condylar block. There were 6 closed, and 2 open fractures (1 grade II and 1 grade IIIB). Following reconstruction of the articular block, the block was indirectly reduced and fixed to the shaft by a plate inserted by the retrograde method beneath the vastus lateralis. Transcutaneous/transmuscular screws were used to fix the plate to the shaft. Time to bone healing was 12 weeks (median range 8-17 weeks) after surgery without needing primary or secondary bone grafts. There were no infections or refractures. Except for one case which required a corrective osteotomy for 10 degrees of varus malalignment, there were no revisions. According to the Neer score, there were 6 excellent or satisfactory results, 2 unsatisfactory results, and no failures. At follow-up, there were 2 varus-valgus deformities greater than 5 degrees, 2 leg length discrepancies greater than 10 mm, and 2 rotational deformities of 15 degrees. The treatment results for complex supracondylar/intracondylar fractures of the distal femur obtained with this technique compare favourably with other reported series using different techniques without the added morbidity associated with autogenous bone grafting. However, the surgical technique is demanding and special care must be taken to ensure correct axial alignment.

Adult↗
PubMed1996

Modeling N-methyl-D-aspartate-induced bursting in dopamine neurons.

Burst firing of dopaminergic neurons of the substantia nigra pars compacta can be induced in vitro by the glutamate agonist N-methyl-D-aspartate. It has been suggested that the interburst hyperpolarization is due to Na+ extrusion by a ouabain-sensitive pump [Johnson et al. (1992) Science 258, 665-667]. We formulate and explore a theoretical model, with a minimal number of currents, for this novel mechanism of burst generation. This minimal model is further developed into a more elaborate model based on observations of additional currents and hypotheses about their spatial distribution in dopaminergic neurons [Hounsgaard (1992) Neuroscience 50, 513-518; Llinás et al. (1984) Brain Res. 294, 127-132]. Using the minimal model, we confirm that interaction between the regenerative, inward N-methyl-D-aspartate-mediated current and the outward Na(+)-pump current is sufficient to generate the slow oscillation (approximately 0.5 Hz) underlying the burst. The negative-slope region of the N-methyl-D-aspartate channel's current-voltage relation is indispensable for this slow rhythm generation. The time-scale of Na(+)-handling determines the burst's slow frequency. Moreover, we show that, given the constraints of sodium handling, such bursting is best explained mechanistically by using at least two spatial, cable-like compartments: a soma where action potentials are produced and a dendritic compartment where the slow rhythm is generated. Our result is consistent with recent experimental evidence that burst generation originates in distal dendrites [Seutin et al. (1994) Neuroscience 58, 201-206]. Responses of the model to a number of electrophysiological and pharmacological stimuli are consistent with known responses observed under similar conditions. These include the persistence of the slow rhythm when the tetrodotoxin-sensitive Na+ channel is blocked and when the soma is voltage-clamped at -60 mV. Using our more elaborate model, we account for details of the observed frequency adaptation in N-methyl-D-aspartate-induced bursting, the origin of multiple spiking and bursting mechanisms, and the interaction between two different bursting mechanisms. Besides reproducing several well established firing patterns, this model also suggests that new firing modes, not yet recorded, might also occur in dopaminergic neurons. This model provides mechanistic insights and explanations into the origin of a variety of experimentally observed membrane potential firing patterns in dopaminergic neurons, including N-methyl-D-aspartate-induced bursting and its dendritic origin. Such a model, capable of reproducing a number of realistic behaviors of dopaminergic neurons, could be useful in further studies of the basal ganglia-thalamocortical motor circuit. It may also shed light on bursting that involves N-methyl-D-aspartate channel activity in other neuron types.

Algorithms↗
PubMed1996

Single-domain/bound calcium hypothesis of transmitter release and facilitation.

1. We describe a model of transmitter release that is based on the finding that release can be gated during the opening of individual Ca2+ channels, suggesting that the release site can be activated by the Ca2+ domain under a single channel. In this model each release site contains four independent Ca2+ binding sites or gates with unbinding kinetics graded from slow to fast and affinities ranging from high to low. All four gates must be bound for release to occur. Thus synaptic dynamics are governed by the kinetics of Ca2+ binding and unbinding from release sites, not Ca2+ diffusion. 2. Fast facilitation occurs when an action potential invades a terminal with one or more ions remaining bound to the release sites. Residual free Ca2+ is not necessary for facilitation with this mechanism, but if present it would enhance facilitation by binding to high-affinity gates between pulses. 3. This model can account for key features of release. These include fourth-power cooperativity with regard to external Ca2+; a release time course that is virtually independent of an increase in quantal content; an inverse relation between external Ca2+ and the degree of facilitation; and a steplike increase in facilitation with increasing stimulus frequency, with each step corresponding to a unitary decline in the Ca2+ cooperativity. 4. Facilitation of single-channel-based secretion is shown to be robust even if channel opening is stochastic. Spontaneous release of transmitter, assumed to be due in part to spontaneous Ca2+ channel openings, is shown to be elevated during and after a train of impulses. 5. An extension of the model to include multiple Ca2+ channels per release site demonstrates that one role of overlapping Ca2+ domains may be to accentuate depolarization-evoked release relative to spontaneous release.

Action Potentials↗
PubMed1995

Topological and phenomenological classification of bursting oscillations.

We describe a classification scheme for bursting oscillations which encompasses many of those found in the literature on bursting in excitable media. This is an extension of the scheme of Rinzel (in Mathematical Topics in Population Biology, Springer, Berlin, 1987), put in the context of a sequence of horizontal cuts through a two-parameter bifurcation diagram. We use this to describe the phenomenological character of different types of bursting, addressing the issue of how well the bursting can be characterized given the limited amount of information often available in experimental settings.

Animals↗