Influence of Dendritic Morphology on Neuronal Electrophysiology

Why is it so important to model neuronal anatomy in detail? Neuroscientists are convinced that dendritic morphology plays an important role in neural computation, but there are very few attempts to investigate this role quantitatively. We are systematically studying the effect of the geometry and topology of neurons on their electrical behavior by means of computational simulations.
firing tracesWe took several experimentally traced neurons from a public electronic archive, converted them for use with the GENESIS simulator, and loaded them with a standard model for their morphological class (CA3 pyramidal cell's Traub model). We paid special attention in setting the exact same distributions of electrophysiological properties (e.g. ionic concentrations and conductances) in all the neurons. Then we started stimulating them (with somatic current injections) with an identical protocol for all of the cells. Thus, every single parameter was constant across these neurons, aside from their dendritic morphology. This variability was sufficient to cause both qualitative and quantitative differences in the firing output of the neurons. Different qualitative behaviors were observed as distinct types of firing modes (regular spiking, as for the two top cells, or train bursting, as in the two bottom cells). Within each mode, there were dramatic quantitative differences (as in the spiking rate between the two top cells, or in the baseline within a burst, in the bottom cells). This project aims at quantifying the exact relationships between morphological and physiological parameters.

Recently, we started applying this research method to the study of the involvement of dendritic morphology in the abnormal neuronal electrophysiology at the basis of Alzheimer's Disease, in a project supported by the Krasnow Institute and by Award No. 00-1 from the Commonwealth of Virginia’s Alzheimer’s and Related Diseases Research Award Fund, administered by the Virginia Center on Aging, Virginia Commonwealth University.

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