UC Davis

Oscillations in olfactory bulb activity are modulated by neurodegenerative disease pathology. Particularly, Alzheimer's disease pathology has been found to strengthen the gamma-band oscillatory activity that arises from the interface between mitral and granule cells. Using two different computational models of the olfactory bulb network, this work investigates the effect of synaptic damage on olfactory bulb gamma oscillations and explores various mechanisms involved in gamma oscillation generation. The first model treats the olfactory bulb as a set of coupled nonlinear oscillators and propagates synaptic weight degradation locally and globally. Gamma oscillations are enhanced at moderate levels of damage, followed by a loss of oscillatory activity predictable by linearized analysis. The second set of simulations uses the large-scale mechanistic model presented by Kersen, Tavoni, and Balasubramanian, implementing Izhikevich dynamical equations. This work adds synapse-specific graded inhibition to the mitral cells, resulting in activity-dependent inhibition critically involving granule cell NMDA current, similar to recent experimental findings. The modified model also implements tonic inhibition to the granule cell population, which reduces granule cell firing and increases mitral cell spike participation and network synchrony. The present iterations of this model do not yield robust gamma oscillations. However, the same model framework could feasibly achieve gamma activity via an entrainment mechanism by using resonant mitral cells with subthreshold oscillations. Finally, the last chapter proposes an extension of the model that implements inhibition-dependent backpropagation of mitral cell action potentials. Previous work theorized that such a mechanism could underlie the increased gamma power and decreased gamma frequency which is observed after modest application of GABA antagonist, an experimental result not yet captured by computational modeling. Thus this work aims to provide critical elements and potentially fruitful directions in the continued investigations of the generation and perturbation of olfactory bulb gamma oscillations.