Mathematical model for frequency modulation in the respiratory network
© Toporikova and Butera; licensee BioMed Central Ltd. 2011
Published: 18 July 2011
Neuromodulators, such as amines and neuropeptides, alter the activity of neurons and neuronal networks. In this work, we investigate how neuromodulators which activate G-proteins and second messenger systems can modulate the frequency of bursting neurons in a critical portion of the respiratory neural network, the pre-Bötzinger complex (pBC). Inspiratory neurons in the pBC produce a regular bursting rhythm in phase with the activity of inspiratory muscles in the diaphragm. These neurons are a vital part of the ponto-medullary neuronal network, which generates a stable respiratory rhythm . The frequency of pBC depends on the concentration of Serotonin (5-HT) and Substance P (SP), neurotransmitters released by the nearby Raphe nucleus. Both neurotransmitters, 5-HT and SP, affect pBC neurons by activating receptors coupled with the G q protein pathway, thereby inducing Ca 2 + release from the Endoplasmic Reticulum (ER).
We have previously developed a mathematical model of the pBC neuron, which incorporates explicit activation of G q -protein coupled receptors, and have shown that activation of these receptors can result in Ca 2 + oscillations in the dendritic compartment . The model exhibits two independent bursting mechanisms – bursting in the soma depends on persistent sodium current, whereas bursting in the dendrite follows Ca 2 + oscillations. It has been recently found that the connection between the pBC and the Raphe nucleus is bi-directional: not only does the Raphe nucleus release 5-HT and SP to modulate the frequency of pBC neurons, but also the rhythmic activity in the pBC increases the firing of Raphe neurons . In this work, we extend our model to a network of pBC neurons while incorporating this newly discovered interaction between Raphe and pBC nuclei.
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