ERC: A New Type of Spike: Homoclinic Spike Generation in Cells and Networks (ANewSpike)

The project addresses the interaction of the nerve cells in our brain. The cells “talk” to each other by means of electrical pulses, so-called action potentials. In this project a new type of action potential dynamics will be investigated, which so far has been widely overlooked in neurobiological research. For this purpose, the nerve cells will be examined with the help of mathematical models and computer simulations. Bridging from the level of individual nerve cells to the level of neural networks will reveal whether this unexplored type of pulse dynamics is an integral part of signal processing in the healthy and diseased brain. Action potentials are not all equal. Despite shared biophysical principles and even similar action-potential shape, neurons with different spike generators can encode vastly different aspects of a stimulus and result in radically different behaviours of the embedding network. Differences between spike generators may be hard to discern because the information content of a spike train is not obvious to the naked eye. This is where computational analysis comes into play: theoretical research has shown that spike generation can be classified into a few dynamical types with qualitatively distinct computational properties. Among these, so-called homoclinic spikes – unlike the other commonly considered types – have been largely ignored. Yet, homoclinic spike generators are special because only they react with high sensitivity to inputs during the refractory period. Indeed, it is directly after a spike when homoclinic spikers “listen” best. As we recently demonstrated, this unique property has computationally exciting consequences: it can provoke a dramatic increase in network synchronization in response to minimal changes in physiological parameters, without requiring alterations in synaptic strength or connectivity. Supported by in-vitro evidence for homoclinic spiking in the rodent brain, ANewSpike explores the intriguing hypothesis that this “forgotten” spike generator provides a unifying framework for the induction of epileptic activity by a wide range of physiological trigger parameters, from temperature to energy deprivation. Using a theory-experiment approach, we explore (i) the prevalence of homoclinic spiking in the brain, (ii) its ability to promote the transmission of high frequencies, and (iii) its ability to boost network synchronization. Our multi-scale study aims to add a novel dimension to our understanding of neural dynamics at the cellular and network level by revealing homoclinic spiking as an integral part of brain dynamics in both health and pathology.