Modelling homeostatic control of intrinsic excitability in single neurons

Yann A. Sweeney, Jeanette Hellgren-Kotaleski, Matthias Hennig

Research output: Contribution to conferencePosterpeer-review


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.
Original languageEnglish
Publication statusPublished - 2012
EventThe Bernstein Conference on Computational Neuroscience 2012 - Klinkum rechts der Isar, Munich, Munich, Germany
Duration: 12 Sep 201214 Sep 2012


ConferenceThe Bernstein Conference on Computational Neuroscience 2012

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