Parallel processing is a common motif in neural sensory systems. In the mammalian olfactory bulb (MOB), odor information from the glomeruli is transmitted by the tufted and mitral cells (TCs and MCs) to different regions of the olfactory cortex, resulting in two parallel odor-processing pathways. The nature and functional significance of information processing performed by each pathway is not understood. Intrinsic cellular and network connectivity differences have been found between the two pathways, and stereotypical MOB gamma oscillation activity (gamma fingerprints) in local field potential recordings have been hypothesized to result from these differences. However, no explanation has been proposed that would mechanistically link the cellular and connectivity differences to the gamma fingerprints. To make progress in understanding the nature of processing by these pathways, we propose a computational modeling approach that will build a rigorously validated, biophysically detailed network model of the MOB containing the TC and MC pathways. The model will be used to systematically manipulate the cellular and connectivity differences to establish their role in the formation of gamma fingerprints. Furthermore, the model will be used to investigate the differences in information processing by the TC and MC sub-systems, by simulating principal cell output and characterizing their differences. The model and the results of the manipulations will result in a mechanistic understanding of information processing by the TC/MC pathways. In the first Specific Aim, published models of MOB cells will be validated against experimental data using the NeuronUnit framework developed in our lab for validating computational models, and models that best approximate experimental observations will be identified and extended. Membrane ion channel conductances and morphologies of TC and MC models then will be systematically manipulated to investigate their contributions to cell behaviors that support the formation of gamma fingerprints. In the second Specific Aim, validated cell models will be used to assemble a network model of the MOB. Lateral connectivity, synaptic properties, and inhibitory interneuron proportions will be systematically manipulated to investigate their contributions to the gamma fingerprints. Under the mentorship of a computational neuroscientist Sponsor and with guidance from a Collaborator with expertise in olfaction research, the proposed project will form the basis of the Principal Investigator's graduate dissertation research. All models will be implemented in NEURON, shared using the modular, simulator-independent language NeuroML, which facilitates discovery, sharing, and reuse of models and their components by other researchers, and will be made available via online model sharing repositories.
The mammalian olfactory bulb is involved in neurodegenerative, mood, and substance abuse disorders. Understanding how the olfactory system functions can lead to better understanding and treatment. Rigorously validated, biophysically detailed computer models provide mechanistic understanding of neural systems, which allows accurate simulations of common (e.g. pharmacological, surgical, and implant) medical intervention modalities.
