Increased oscillatory power in a computational model of the olfactory bulb due to synaptic degeneration

Abstract

Several neurodegenerative diseases impact the olfactory system, and in particular the olfactory bulb, early in disease progression. One mechanism by which damage occurs is via synaptic dysfunction. Here, we implement a computational model of the olfactory bulb and investigate the effect of weakened connection weights on network oscillatory behavior. Olfactory bulb network activity can be modeled by a system of equations that describes a set of coupled nonlinear oscillators. In this modeling framework, we propagate damage to synaptic weights using several strategies, varying from localized to global. Damage propagated in a dispersed or spreading manner leads to greater oscillatory power at moderate levels of damage. This increase arises from a higher average level of mitral cell activity due to a shift in the balance between excitation and inhibition. That this shift leads to greater oscillations critically depends on the nonlinearity of the activation function.Linearized analysis of the network dynamics predicts when this shift leads to loss of oscillatory activity. We thus demonstrate one potential mechanism involved in the increased gamma oscillations seen in some animal models of Alzheimer's disease and highlight the potential that pathological olfactory bulb behavior presents as an early biomarker of disease. I. INTRODUCTIONThe olfactory system, and in particular the olfactory bulb (OB), is implicated in early stages of a number of neurodegenerative diseases, including two of the most prevalent, Alzheimer's disease (AD) and Parkinson's disease (PD) [1][2][3]. In both AD and PD, olfactory deficits occur years before diagnosis and often before other symptoms [2,[4][5][6][7][8][9]. Furthermore, the OB is a site of early pathology in both diseases [7,[10][11][12][13][14][15], with resulting aberrant neural activity [16][17][18][19][20][21]. We hope that computationally modeling olfactory bulb activity in diseaselike conditions can help to further shed light on mechanisms of dysfunction, identify markers of disease, and bring attention to the opportunity the OB presents for earlier diagnosis of neurodegenerative illnesses.The OB is the first processing area for incoming odor information [22], but exactly how it is represented is an ongoing question for which there are various theories, mainly revolving around combinatorics of principal neuron activity [23][24][25][26]. Oscillations in neural activity in