Event Abstract Back to Event Site of spike initiation changes with functional context in coincidence detector neurons Simon Lehnert1* and Christian Leibold1, 2 1 Ludwig-Maximilians-Universität München, Department of Biology II, Germany 2 Bernstein Center for Computational Neuroscience Munich, Germany Principal cells of the medial superior olive (MSO) are very fast coincidence detectors in the auditory brainstem that encode interaural time differences by their firing rate. Their enormously low time constant of only a few hundred microseconds is caused by the very low input resistance of about 5MΩ at rest [1], which arises from the expression of low-voltage-activated potassium channels (KLVA) and hyperpolarization-activated unspecific cation channels (HCN). Spike initiation is generally assumed to occur in the axon's initial segment (AIS). However, in neurons with very low input resistance, as in the MSO, this may no longer hold true, because the soma constitutes an enormous current sink. Moreover, these cells receive a huge amount fast excitation and slowly-decaying inhibition at rates up to 2 kHz, such that their input resistance in vivo is even much smaller than at rest. Hence the questions arise: how are these cells able to elicit action potentials (APs)? And, how are these cells able to uphold their biological function? By using a multi-compartmental model of an MSO cell and its axon, we found that, at rest, the spike initiation segment (SIS) in the model is indeed the AIS, because the electrotonic independence of the AIS from the leaky soma results in an input resistance of the axonal segments that is considerably higher than at the soma. For higher input conductances, as they are obtained by simulating naturalistic synaptic activity, the SIS can also be found further distal in the axon. This is because the excitatory and inhibitory conductances by themself and via opening KLVA and HCN channels, respectively, reduce the excitability of the AIS, while more distal axonal regions are much less affected. We conclude that, although in cases where the AIS itself is not excitable, the deeper axon is, and enables the cell to convey information downstream. We show that the cells ability to initiate spikes distally enhances the dynamic range of the generated rate code. Moreover, the model suggests that especially the low rate part of the code is mostly established by distally initiated AP responses.