During the last two years we have made substantial progress in shedding light on these action potentials’ generation and function. Specifically: 1) We have revealed that concentration increases in extracellular potassium ions push neurons into this dynamical regime. This was shown in mathematical models and confirmed in in-vitro experiments in collaboration with the lab of Allen Gulledge (Vanderbilt University, US), see publication Contreras et al., PLoS Computational Biology (2021). 2) We have demonstrated that moderate elevations above physiological temperature can also induce homoclinic spiking. Moreover, we have shown that this type of spike tends to synchronize inhibitory networks and to induce splayed-out, desynchronized states in excitatory networks. Again, the basis forms the mathematical model, an initial experimental confirmation of the switch to homoclinic spikes in hippocampal cells was obtained in collaboration with the lab of Dietmar Schmitz (Charite Berlin, Germany). The results were published in Hesse et al., Nature Communications (2022). 3) As we had found out before the start of the ERC project, also changes in membrane capacitance can induce homoclinic spikes. Membrane capacitance, however, cannot be easily modulated. Hence, we developed a hybrid experimental-in-silico method to artificially modulate membrane capacitance in in-vitro experimental settings. This technique, called 'capacitance clamp’ was applied in collaboration with the lab of Imre Vida (Charite Berlin, Germany) and the results have been published in Pfeiffer et al., eLife (2022). 4) We have mathematically derived the firing statistics of neurons with homoclinic spikes, see Schleimer et al., Phys Rev E (2021). These provide an additional dimension to distinguish homoclinic spikers from other dynamical types. 5) Based on mathematical analysis, we derived a novel desynchronizing effect of neurons with homoclinic spikes when coupled electrically via gap junctions.
