The Neuron as a Cell: Can IP3 Mediated Dendritic Ca2+ Waves Contribute to Altered Integration and Persistent Activity in Cortical Neurons?

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Second messenger-mediated intracellular Ca2+ release mechanisms will be incorporated into detailed compartment models of cortical pyramidal cells. The investigators, as well as others, have observed these waves of Ca2+ release in neuronal dendrites experimentally, and these detailed cellular models will be used to replicate the waves, investigate their function, and make predictions for future experiments. The key novel aspect of this work is linking the nonlinear dynamics of the intracellular signaling pathways to the electrical behavior of the neuron. This represents a fundamental shift because changes related to intracellular signaling have largely been implemented as static parameter changes in past neurocomputational models. Detailed biophysical models will enable the investigators to test whether the internal neuronal biochemistry can function to alter integration properties of cortical neurons and whether these intracellular processes can affect the behavior of networks of neurons.The problem of intracellular Ca2+ signaling in neurons has immediate relevance for understanding mechanisms of plasticity and for understanding disease processes that are known to involve malfunctions of intracellular signaling pathways. Reusable tools will be crafted for the NEURON general-purpose simulator that will allow others to extend widely different neural models with intracellular signaling mechanisms and explore a variety of related problems. In terms of broader impact, the project will bring together the fields of computational neuroscience and computational cell biology - communities that do not currently overlap a great deal - in order to start to investigate the many aspects the function of neurons not currently addressed by theoretical neuroscience. As part of this work, research experience opportunities for undergraduate diversity programs will be provided at the University of Illinois at Chicago.