Investigating the roles of sodium pumps in healthy and MND-affected spinal neurons using human iPSCs and animal models

We have recently shown that the ubiquitous Na+-K+ exchange pump plays an important role in adapting neural networks in an activity-dependent and homeostatic manner. Within spinal locomotor networks, we found that Na pumps mediate a long-lasting, activity-dependent hyperpolarisation, which provides a form of short-term memory of previous network activity that shapes future network performance (Picton et al., J Neurosci, 2017). In this fully-funded PhD studentship we intend to utilise electrophysiological and live calcium imaging techniques applied to animal models and human induced pluripotent stem cells (iPSCs), to test the hypothesis that pump-mediated memory is critical to prevent neural fatigue, and that sodium pumps provide strategic targets for neuromodulators which promote flexibility in neural network function. Na pumps are also implicated in numerous diseases, including Motor Neuron Disease (MND). We therefore also aim to investigate whether sodium pump function is perturbed in animal and human iPSC-based models of MND. We hypothesise that changes in Na pump-mediated hyperpolarisations may contribute to altered motoneuron excitability that we (Devlin et al., 2015, Nat Commun) and others have observed in MND models and that Na pumps may therefore serve as an important target for the development of new treatments for MND.
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