Abstracts

Davison A.P., Zhou Z., Hines M.L. and Shepherd G.M. (2001) Simulating sodium and potassium currents in an olfactory mitral cell model. Slide presentation at the Society for Neuroscience Annual Meeting, San Diego, California, November 2001.

We have previously developed a tightly constrained model of the olfactory mitral cell based on dual patch recordings in rat olfactory bulb slices (Shen et al, J. Neurophysiol. 82: 3006-3020, 1999). The model closely simulates action potential generation at somatic and dendritic sites based on a transient Na and delayed rectifier K current. In order to extend this model for other membrane currents, we have carried out a combined experimental (patch-clamp) and modeling study. The response to long-duration, perithreshold current injection from a hyperpolarized resting potential has three main characteristics: (i) a delay of up to several hundred milliseconds before action potential firing; (ii) an inflection or overshoot in the membrane potential rise phase; (iii) subthreshold membrane potential oscillations. With suprathreshold stimulation the firing frequency increases with time, i.e. negative adaptation. These characteristics suggest the presence of a slowly-inactivating K current and a persistent Na current. We are extending the previous model in order to test these hypotheses by characterizing the membrane currents and analysing the contribution each makes to the observed behaviour. Channel kinetics and channel density distribution are obtained by fitting the model to the experimental recordings. Channel kinetics are also obtained by voltage clamp recordings and there is good agreement between the parameters obtained by the two methods. The results will lead to simulations of the firing patterns of the mitral cell over time, so that models of synaptic activation and mitral-granule cell networks can be constructed.
Supported by: NIDCD and NIMH (Human Brain Project).

Davison A.P. and Feng J. (2001) A model of network interactions in the olfactory bulb. Poster presentation at AChemS XXIII, Sarasota, Florida, April 2001.

We have developed a detailed, biologically-realistic model of the mammalian olfactory bulb, incorporating the mitral and granule cells and the dendrodendritic synapses between them. The individual cell models were simplified from detailed compartmental models which had been fitted to experimental data. The amplitudes, time courses and transmission delays of the synapses were obtained from the literature. A simple method for specifying the synaptic connections was adopted, based on the limited experimental data in the literature on the statistics of connections between neurons in the bulb. Both electrical and odor stimulation were modeled. A simple model of olfactory inputs was used which captures some qualitative aspects of odor inputs but which is not necessarily quantitatively accurate.
As a test of the model, a series of simulation experiments with electrical stimulation were performed and the results agreed quite closely with published experimental data which were not used in developing the model. This gives confidence that the model is capturing some features of network interactions in the real olfactory bulb. Simulation experiments with `odor' stimulation were then performed to investigate: (i) how the model response (in terms of synchronization and the spatial distribution of activity) is affected by stimulus intensity; (ii) how the response depends on connectivity parameters; and (iii) whether the network makes it easier to discriminate between similar odor inputs.

Davison A.P. (2001) Mathematical modelling of information processing in the olfactory bulb. Ph.D. thesis, University of Cambridge.

The aim of this dissertation is to investigate the processing of sensory signals in the mammalian olfactory bulb, using analysis and computer simulation of mathematical models. A biologically-detailed mathematical model provides a framework which integrates the results of experiments at different levels of enquiry, and enables study of problems which cannot easily be addressed using only the methods of experimental neuroscience.
Specific biological and computational problems which are addressed include: the existence, origin and role of oscillations/synchronisation; how the properties of individual cells/synapses influence the network behaviour; the role of lateral inhibition; how the connectivity between cells influences network behaviour.
The dissertation has four main parts: (i) a review of the anatomy and physiology of vertebrate olfactory systems, and of previous modelling studies of the olfactory bulb; (ii) development of biophysical models of the principal neurone types of the olfactory bulb, based closely on experimental data, but simple enough to allow simulation of large networks; (iii) an examination of the fundamental interaction in the bulb -- that between two mitral cells -- using simulation of the biophysical cell models and analysis of the simpler integrate-and-fire neurone model; (iv) development of network models of the olfactory bulb incorporating the biophysical neurone models. These are tested using experimental data from the literature, and then the properties of the network are studied, leading to predictions which could be tested experimentally.

Davison A.P., Feng J. & Brown D. (2001) Spike synchronization in a biophysically-detailed model of the olfactory bulb. Neurocomputing 38-40: 515-521

Stimulus-evoked synchronization of action potentials has been demonstrated in mammalian olfactory bulb and in insect antennal lobes. Abolition of synchronization has been shown to impair the ability of honeybees to perform fine olfactory discrimination. We present a biophysically-detailed computer model of the olfactory bulb which qualitatively reproduces many features seen in experimental recordings. The mitral cells of the model synchronize readily without common input due to lateral interactions with inhibitory granule cells. Weakly activated mitral cells fire more slowly than, but always synchronously with, strongly activated cells. Nearby cells synchronize more readily than widely-separated ones.

Davison A.P., Feng J. & Brown D. (2000) A reduced compartmental model of the mitral cell for use in network models of the olfactory bulb. Brain Research Bulletin 51(5): 393-399

We have developed two-, three- and four-compartment models of a mammalian olfactory bulb mitral cell as a reduction of a complex 286-compartment model. A minimum of three compartments, representing soma, secondary (basal) dendrites and the glomerular tuft of the primary dendrite, is required to adequately reproduce the behaviour of the full model over a broad range of firing rates. Adding a fourth compartment to represent the shaft of the primary dendrite gives a substantial improvement. The reduced models exhibit behaviours in common with the full model which were not used in fitting the model parameters. The reduced models run 75 or more times faster than the full model, making their use in large, realistic network models of the olfactory bulb practical.

Keywords: olfaction, single-neuron models, simplified models, biological neural networks.

Davison A.P., Feng J. & Brown D. (1999) Structure of lateral inhibition in an olfactory bulb model. Lecture Notes in Computer Science, 1606: 189-196.

It has been shown that mutual lateral inhibition of the projection neurones in the olfactory bulb, mediated by interneurones, serves to tune the representation of odours in the bulb and reduce the overlap between similar odorants. In this paper we demonstrate that the parameters of the lateral interaction, specifically the relation of synaptic strength to cell separation and the effective overall gain of the network, have a significant effect on the strength and range of lateral inhibition in a simple model of the olfactory bulb.