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Biomedical subjects

M C Vanier

Publications and source records attributed to M C Vanier.

5 recordsLinked to original sources

On the use of Bayesian methods for evaluating compartmental neural models.

Computational modeling is being used increasingly in neuroscience. In deriving such models, inference issues such as model selection, model complexity, and model comparison must be addressed constantly. In this article we present briefly the Bayesian approach to inference. Under a simple set of commonsense axioms, there exists essentially a unique way of reasoning under uncertainty by assigning a degree of confidence to any hypothesis or model, given the available data and prior information. Such degrees of confidence must obey all the rules governing probabilities and can be updated accordingly as more data becomes available. While the Bayesian methodology can be applied to any type of model, as an example we outline its use for an important, and increasingly standard, class of models in computational neuroscience--compartmental models of single neurons. Inference issues are particularly relevant for these models: their parameter spaces are typically very large, neurophysiological and neuroanatomical data are still sparse, and probabilistic aspects are often ignored. As a tutorial, we demonstrate the Bayesian approach on a class of one-compartment models with varying numbers of conductances. We then apply Bayesian methods on a compartmental model of a real neuron to determine the optimal amount of noise to add to the model to give it a level of spike time variability comparable to that found in the real cell.

Action Potentials

The role of axonal delay in the synchronization of networks of coupled cortical oscillators.

Coupled oscillator models use a single phase variable to approximate the voltage oscillation of each neuron during repetitive firing where the behavior of the model depends on the connectivity and the interaction function chosen to describe the coupling. We introduce a network model consisting of a continuum of these oscillators that includes the effects of spatially decaying coupling and axonal delay. We derive equations for determining the stability of solutions and analyze the network behavior for two different interaction functions. The first is a sine function, and the second is derived from a compartmental model of a pyramidal cell. In both cases, the system of coupled neural oscillators can undergo a bifurcation from synchronous oscillations to waves. The change in qualitative behavior is due to the axonal delay, which causes distant connections to encourage a phase shift between cells. We suggest that this mechanism could contribute to the behavior observed in several neurobiological systems.

Axons

Biological rhythms in pain and in the effects of opioid analgesics.

Pain is difficult and sometimes frustrating to treat, even though new devices and new approaches have been developed in recent years. Pain varies tremendously from one patient to the next, and there are also some studies suggesting that the intensity of pain varies according to time of day. In animal experiments, a relationship between the reaction to pain and the rhythmicity of plasma endorphin concentrations was suggested because reactions to pain (such as jumping from a hot plate) were in phase with plasma endorphin levels: latencies were longest and plasma levels were highest during the resting period of rodents. In human studies, pain induced experimentally was reported to be maximal in the morning, or in the afternoon or at night. These divergent findings may be due to methodological differences, as pain was produced by different methods, many parameters were used to quantify pain intensity, and the psychological aspect of pain was rarely considered by authors. A circadian pattern of pain was found in patients suffering from pain produced by different diseases. For instance, highest toothache intensity occurred in the morning, while biliary colic, migraine, and intractable pain were highest at night. Patients with rheumatoid arthritis reported peak pain early in the morning, while those with osteoarthritis of the knee indicated that the maximal pain occurred at the end of the day. The effectiveness of opioids appears also to vary according to time of day, but large differences in the time of peak and low effects were found. Investigators found that peak pain intensity and narcotic demands occurred early in the morning, while others found maximal pain at the end of the day. Pain is a complex phenomenon and efforts should be made to standardize the methods used in studies and to describe accurately the diseases causing pain because the patterns of pain may be specific to each clinical situation. Further research should be aimed at characterizing the chronobiology of pain in different experimental and clinical situations and to determine when the analgesic drugs are producing maximal effectiveness. This information is needed before clinicians can be persuaded to use chronopharmacological data when they prescribe analgesic drugs to their patients.

Analgesics, Opioid

Retinoic acid inhibits phospholipid turnover and protein kinase C activity in RA-sensitive but not in RA-resistant cells.

Treatment with 10(-5) M retinoic acid causes loss of anchorage-independent growth in src-transformed RR1022 cells but not in ras-transformed KNRK cells. In an effort to elucidate the mechanisms underlying this difference, we investigated the effect of RA on phospholipid turnover and PKC activity in these two cell lines. 10(-5) M RA treatment caused a drastic inhibition of 32P incorporation into PI and PA and a large increase in 32P incorporation into PC in RR1022 cells. Similar treatment of KNRK cells yielded no change in PC or PA labelling and a much smaller decrease in PI labelling. Furthermore, 10(-5) M RA treatment causes a large decrease in PKC activity in RR1022 cells (35% of control) but only a small decrease in KNRK cells (78% of control). We suggest that these effects are part of an altered signal transduction pathway which mediates the differential effects of RA on anchorage-independent growth in these two cell lines.

Animals