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Geometrical aspects of action potential initiation

Mustafa S. Hamada1, 2, Romain Brette3 and Maarten H. Kole1, 2*
  • 1 Netherlands Institute for Neuroscience, Axonal Signalling, Netherlands
  • 2 University of Utrecht, Cellular Biology, Netherlands
  • 3 Institut de la Vision, France

The initiation of action potentials (APs) is a fundamental operation of the nervous system. In most excitable cells, the temporally precise transfer of incoming synaptic signals into meaningful AP rate and temporal codes is produced within axons. Axonal AP initiation is mediated by clustering of high densities of sodium channels to the axon initial segment (AIS) generating a back-propagating AP evolving into the somato-dendritic AP (Kole and Stuart, 2012). Besides the eminent role of high-density sodium channel clustering recent computational work indicates that specific cable properties of the axon and dendrites may play additional and complex roles during initiation. On the one hand, the rising phase of the local axonal AP is accelerated by the axial resistance and non-uniform voltage gradients between the AIS and soma (Brette, 2013). On the other hand, during steady-state action potential firing the large dendritic tree can impose a current sink for antidromically propagating action potentials invading the dendrites (Hay et al., 2013). To accommodate for the cell-to-cell variability of dendritic trees it was hypothesized that the sodium channel density in the soma and AIS scales proportionally with the degree of dendritic conductance load (Hay et al., 2013). Whether this occurs biologically is not known. A confounding factor in most compartmental models is the limited number of variables which can be empirically collected from an individual neuron. Here, our recent advances in modelling optimization will be discussed. Whole-cell patch-clamp recordings were obtained from thick-tufted layer 5 pyramidal neurons in rodent brain slices (300 µm), cells filled with biocytin and recorded for action potential properties and subthreshold voltage transients. Slices were subsequently fixed and stained for AIS-specific anchoring protein markers and biocytin-streptavidin to collect detailed information about the geometrical properties and position of the AIS and nodes of Ranvier. High-resolution confocal laser-scanning microscopy was used to sample the branch pattern of the axonal and dendritic trees and integrate the immunofluorescence data into the three-dimensional reconstructions, allowing an accurate representation of the axonal subdomains within a morphologically realistic conductance-based compartmental model (Hamada and Kole, 2015). Finally, the recorded subthreshold voltage transients and APs were used to constrain the conductance densities in the model. In this talk, I will discuss about the possibility of generic geometrical scaling rules and show how the AIS, in part, may compensate for both the capacitive and conductance load of the dendritic tree.

Acknowledgements

The investigation was supported by a European Research Council Starting Grant (ERC-StG #261114) to M.H.P.K. and an Agence Nationale de la Recherche grant (ANR-14-CE13-0003) to R.B.

References

Brette, R. (2013). Sharpness of spike initiation in neurons explained by compartmentalization. PLoS Comput Biol 9, e1003338. doi:10.1371/journal.pcbi.1003338.
Hamada, M. S., and Kole, M. H. P. (2015). Myelin loss and axonal ion channel adaptations associated with gray matter neuronal hyperexcitability. J Neurosci 35, 7272–7286. doi:10.1523/JNEUROSCI.4747-14.2015.
Hay, E., Schürmann, F., Markram, H., and Segev, I. (2013). Preserving axosomatic spiking features despite diverse dendritic morphology. J Neurophysiol 109, 2972–2981. doi:10.1152/jn.00048.2013.
Kole, M. H. P., and Stuart, G. J. (2012). Signal processing in the axon initial segment. Neuron 73, 235–247. doi:10.1016/j.neuron.2012.01.007.

Keywords: Axon, action potential initiation, compartmental modeling, geometry, axon initial segment, layer 5 pyramidal cell

Conference: Spike Initiation: Models & Experiments, Prague, Czechia, 22 Jul - 22 Jul, 2015.

Presentation Type: Oral Presentation

Topic: Neuroscience

Citation: Hamada MS, Brette R and Kole MH (2015). Geometrical aspects of action potential initiation. Front. Neurosci. Conference Abstract: Spike Initiation: Models & Experiments. doi: 10.3389/conf.fnins.2015.90.00005

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Received: 07 Jul 2015; Published Online: 07 Jul 2015.

* Correspondence: Prof. Maarten H Kole, Netherlands Institute for Neuroscience, Axonal Signalling, Amsterdam, 1105 BA, Netherlands, m.kole@nin.knaw.nl