Exploring parameter space in detailed single neuron models: Simulations of the mitral and granule cells of the olfactory bulb

U. S. Bhalla, J. M. Bower

Resultado de la investigación: Articlerevisión exhaustiva

151 Citas (Scopus)


1. Detailed compartmental computer simulations of single mitral and granule cells of the vertebrate olfactory bulb were constructed using previously published geometric data. Electrophysiological properties were determined by comparing model output to previously published experimental data, mainly current-clamp recordings. 2. The passive electrical properties of each model were explored by comparing model output with intracellular potential data from hyperpolarizing current injection experiments. The results suggest that membrane resistivity in both cells is nonuniform, with somatas having a substantially lower resistivity than the dendrites. 3. The active properties of these cells were explored by incorporating active ion channels into modeled compartments. On the basis of evidence from the literature, the mitral cell model included six channel types: fast sodium, fast delayed rectifier (Kfast), slow delayed rectifier (K), transient outward potassium current (KA), voltage- and calcium-dependent potassium current (KCa), and L-type calcium current. The granule cell model included four channel types: rat brain sodium, K, KA, and the non-inactivating muscarinic potassium current (KM). Modeled channels were based on the Hodgkin-Huxley formalism. 4. Representative kinetics for each of the channel classes above were obtained from the literature. The experimentally unknown spatial distributions of each included channel were obtained by systematic parameter searches. These were conducted in two ways: large-scale simulation series, in which each parameter was varied in turn, and an adaptation of a multidimensional conjugate gradient method. In each case, the simulated results were compared with experimental data using a curve-matching function evaluating mean squared differences of several aspects of the simulated and experimental voltage waveforms. 5. Systematic parameter variations revealed a single distinct region of parameter space in which the mitral cell model best fit the data. This region of parameter space was also very robust to parameter variations. Specifically, optimum performance was obtained when calcium and slow K channels were concentrated in the glomeruli, with a lower density in the soma and proximal secondary dendrites. The distribution of sodium and fast potassium channels, on the other hand, was highest at the soma and axon, with a much lighter distribution throughout the secondary dendrites. The KA and KCa channels were also concentrated near the soma. 6. The parameter search of the granule cell model was much less restrained by experimental data. Several parameter regimes were found that gave a good match to the data. In the simplest of these, sodium and K channels were present at high density both at the soma and in the peripheral dendrites, whereas the KA and KM channels were present only in the soma. 7. Further manipulation of the mitral cell model suggests that the predicted channel distributions can be verified physiologically. If the channel distributions suggested by the model are correct, voltage clamping the soma to potentials near the spiking threshold should result in the generation of independent local dendritic action potentials reflecting the effective decoupling of the active membranes of the different dendrites. The model predicts that the glomerular tuft, the soma, and the secondary dendrites of each mitral cell have distinct local electrical properties resulting largely from the localized distribution of ion channels. They may also be functionally distinct. 8. Our extensive search of model parameters suggests that neurons operate in regions of parameter space that are most robust to changes in parameter values. In particular, changes in channel densities by as much as an order of magnitude may have relatively little effect on the behavior of the neuronal model.

Idioma originalEnglish (US)
Páginas (desde-hasta)1948-1965
Número de páginas18
PublicaciónJournal of neurophysiology
EstadoPublished - 1993

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology


Profundice en los temas de investigación de 'Exploring parameter space in detailed single neuron models: Simulations of the mitral and granule cells of the olfactory bulb'. En conjunto forman una huella única.

Citar esto