Projektbeschreibung
Forschung zu neuronaler Dynamik und Induktion epileptischer Aktivität
Modelle von Gehirnfunktionen müssen immer auch die Variabilität bei der Erzeugung neuronaler Aktionspotenziale (Spikes) mitberücksichtigen. Computergestützten Untersuchungen zufolge lassen sich die unterschiedlichen Spike-Generatoren einigen wenigen dynamischen Typen mit jeweils computerspezifischen Merkmalen zuordnen. Insbesondere Generatoren homokliner Spikes reagieren speziell in der neuronalen Refraktärperiode hochempfindlich auf Inputs. Das EU-finanzierte Projekt ANewSpike baut auf wissenschaftlichen Daten zu homoklinen Spikes im Gehirn von Nagetieren auf und untersucht die spannende Hypothese, dass sich diese Spike-Generatoren als universeller Rahmen eignen, um epileptische Aktivität über zahlreiche physiologischer Trigger wie Temperatur oder Energiedeprivation zu induzieren. Die aktuelle Studie erweitert das bisherige Wissen über neuronale Dynamik um eine neue Dimension und etabliert homokline Spikes als integralen Bestandteil der Gehirndynamik.
Ziel
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 behaviors 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.
Wissenschaftliches Gebiet
Programm/Programme
Thema/Themen
Finanzierungsplan
ERC-COG - Consolidator GrantGastgebende Einrichtung
10117 Berlin
Deutschland