Descripción del proyecto
Dinámica neuronal e inducción de la actividad epiléptica
Cualquier modelo de la función encefálica tiene en consideración la variedad de la generación o activación de los impulsos neuronales. La investigación computacional ha demostrado diferencias entre los generadores de impulsos, lo que demuestra que pueden clasificarse en varios tipos dinámicos con distintas propiedades computacionales. En concreto, los generadores de impulsos homoclínicos reaccionan específicamente con alta sensibilidad a estímulos durante el periodo refractario neuronal. El proyecto ANewSpike, financiado con fondos europeos, apoyado por las pruebas de los impulsos homoclínicos en el encéfalo de roedores, estudia la intrigante hipótesis de que dichos generadores de estímulos ofrecen un marco unificador para la inducción de la actividad epiléptica mediante una amplia gama de factores desencadenantes, desde la temperatura a la privación de energía. El estudio actual añade una nueva dimensión a la comprensión de la dinámica neuronal, incluidos impulsos homoclínicos como parte integral de la dinámica encefálica.
Objetivo
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.
Ámbito científico
Programa(s)
Régimen de financiación
ERC-COG - Consolidator GrantInstitución de acogida
10117 Berlin
Alemania