Abstract
Action potential generation and conduction requires large quantities of energy to restore Na+ and K+ ion gradients. We investigated the subcellular location and voltage dependence of this metabolic cost in rat neocortical pyramidal neurons. Using Na+/K+ charge overlap as a measure of action potential energy efficiency, we found that action potential initiation in the axon initial segment (AIS) and forward propagation into the axon were energetically inefficient, depending on the resting membrane potential. In contrast, action potential backpropagation into dendrites was efficient. Computer simulations predicted that, although the AIS and nodes of Ranvier had the highest metabolic cost per membrane area, action potential backpropagation into the dendrites and forward propagation into axon collaterals dominated energy consumption in cortical pyramidal neurons. Finally, we found that the high metabolic cost of action potential initiation and propagation down the axon is a trade-off between energy minimization and maximization of the conduction reliability of high-frequency action potentials.
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Acknowledgements
The research leading to these results has received funding from the European Research Council under the European Community's Seventh Framework Program (FP7/2007–2013)/ERC Grant agreement n° P261114 and from the Australian National Health and Medical Research Council (NHMRC) Project Grant n° 525437 to M.H.P.K. S.H. received funding from the Heisenberg Program of the German Research Foundation (HA 6386/1-1 and 2-1). The authors are grateful to Henrik Alle and Christoph Schmidt-Hieber for discussions on earlier versions of this manuscript.
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S.H. and M.H.P.K. designed and conducted the experiments and analyzed data. C.P.J.d.K. provided the in vivo reconstructions. S.H., C.P.J.d.K., G.J.S. and M.H.P.K. wrote the paper.
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Hallermann, S., de Kock, C., Stuart, G. et al. State and location dependence of action potential metabolic cost in cortical pyramidal neurons. Nat Neurosci 15, 1007–1014 (2012). https://doi.org/10.1038/nn.3132
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DOI: https://doi.org/10.1038/nn.3132
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