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Modelling homeostatic control of intrinsic excitability in single neurons

Yann Sweeney1, 2* and Matthias Hennig1
  • 1 University of Edinburgh, School of Informatics, United Kingdom
  • 2 KTH Royal Institute of Technology, Department of Computational Biology, Sweden

Intrinsic excitability in neurons is controlled by a number of homeostatic mechanisms, among which are the modulation of conductances in voltage-dependent ion channels and the modulation of the distance of the axon initial segment (AIS) from the soma. Due to their large size and good accessibility in slice experiments, a useful model system for these forms of homeostatic regulation are principal neurons of the medial nucleus of trapezoid body (MNTB) in the auditory brainstem. These act as relay neurons, receiving excitatory input and transmitting inhibitory signals to the auditory nuclei involved in sound localisation. One form of homeostasis of intrinsic excitability has been shown to be mediated by Nitric Oxide (NO), which is released by MNTB neurons in an activity-dependent manner and modulates Kv3 and Kv2 potassium channels conductance. We have investigated this homeostatic regulation in a multi-compartment MNTB neuron model, incorporating the localisation of ion channels in the soma and the AIS. The analysis of the model showed that the main effects of NO synthesis, a reduction of excitability and concomitant changes in action potential shape as observed in vitro (Steinert et al., Neuron, 2008, 2011), can be accounted for by increasing Kv2 conductances. Moreover, we found that the localisation of ion channels in the AIS, as opposed to the soma, results in a significantly faster action potential onset, with this effect increasing as the AIS is located more distally to the soma. Consistent with previous reports (Grubb & Burrone, Nature, 2010), the latter also increased neural excitability. We currently investigate how NO synthesis and AIS location affect the integration of synaptic inputs for different average activity levels and other statistical features of the input.

Acknowledgements

MRC Fellowship G0900425
EuroSPIN EMJD Fellowship
EPSRC and BBSRC funded Doctoral Training Centre programme at School of
Informatics, University of Edinburgh

References

[Steinert et al., 2008] Steinert, J. R., Kopp-Scheinpflug, C., Baker, C., Challiss, R. a J., Mistry, R., Haustein, M. D., Griffin, S. J., et al. (2008). Nitric oxide is a volume transmitter regulating postsynaptic excitability at a glutamatergic synapse. Neuron, 60(4), 642-56. Elsevier Inc. doi:10.1016/j.neuron.2008.08.025

[Steinert et al., 2011] Steinert, J. R., Robinson, S. W., Tong, H., Haustein, M. D., Kopp-Scheinpflug, C., & Forsythe, I. D. (2011). Nitric oxide is an activity-dependent regulator of target neuron intrinsic excitability. Neuron, 71(2), 291-305. Elsevier Inc. doi:10.1016/j.neuron.2011.05.037

[Grubb & Burrone, 2010] Grubb, M. S., & Burrone, J. (2010). Activity-dependent relocation of the axon initial segment fine-tunes neuronal excitability. Nature, 465(7301), 1070-4. Nature Publishing Group. doi:10.1038/nature09160

Keywords: axon initial segment, Compartmental neuron model, Homeostasis, Ion Channels, MNTB, Nitric Oxide

Conference: Bernstein Conference 2012, Munich, Germany, 12 Sep - 14 Sep, 2012.

Presentation Type: Poster

Topic: Other

Citation: Sweeney Y and Hennig M (2012). Modelling homeostatic control of intrinsic excitability in single neurons. Front. Comput. Neurosci. Conference Abstract: Bernstein Conference 2012. doi: 10.3389/conf.fncom.2012.55.00239

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Received: 18 Sep 2012; Published Online: 12 Sep 2012.

* Correspondence: Mr. Yann Sweeney, University of Edinburgh, School of Informatics, Edinburgh, Edinburgh, EH8 9AB, United Kingdom, yann.sweeney@ed.ac.uk