From molecular pathways to neural populations: investigations of different levels of networks in the transverse slice respiratory neural circuitry.

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Tsao, Tzu-Hsin B.
Butera, Robert J.
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By exploiting the concept of emergent network properties and the hierarchical nature of networks, we have constructed several levels of models facilitating the investigations of issues in the area of respiratory neural control. The first of such models is an intracellular second messenger pathway model, which has been shown to be an important contributor to intracellular calcium metabolism and mediate responses to neuromodulators such as serotonin. At the next level, we have constructed new single neuron models of respiratory-related neurons (e.g. the pre-Btzinger complex neuron and the Hypoglossal motoneuron), where the electrical activities of the neurons are linked to intracellular mechanisms responsible for chemical homeostasis. Beyond the level of individual neurons, we have constructed models of neuron populations where the effects of different component neurons, varying strengths and types of inter-neuron couplings, as well as network topology are investigated. Our results from these simulation studies at different structural levels are in line with experiment observations. The small-world topology, as observed in previous anatomical studies, has been shown here to support rhythm generation along with a variety of other network-level phenomena. The interactions between different inter-neuron coupling types simultaneously manifesting at time-scales orders of magnitude apart suggest possible explanations for variations in the outputs measured from the XII rootlet in experiments. In addition, we have demonstrated the significance of pacemakers, along with the importance of considering neuromodulations and second-messenger pathways in an attempt to understand important physiological functions such as breathing activities.
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