Descrizione del progetto
Dinamiche neurali e induzione dell’attività epilettica
Qualsiasi modello di funzione cerebrale prende in considerazione la variabilità nella generazione degli spike neuronali, noti anche come scariche neuronali. La ricerca computazionale ha dimostrato l’esistenza di differenze tra i generatori di spike e ha evidenziato che questi possono essere classificati in varie tipologie dinamiche con proprietà computazionali distinte. In particolare, i generatori di spike omoclinici reagiscono specificamente e con elevata sensibilità agli input durante il periodo refrattario neuronale. Grazie al sostegno fornito da evidenze di spiking omoclinico nell’encefalo di roditori, il progetto ANewSpike, finanziato dall’UE, indaga l’interessante ipotesi che tali generatori di spike forniscano un quadro unificatore per l’induzione dell’attività epilettica causata da una vasta gamma di fattori fisiologici scatenanti, dalla temperatura fino alla privazione di energia. Lo studio attuale aggiunge una nuova dimensione alla comprensione delle dinamiche neurali, e considera gli spike omoclinici una parte integrante delle dinamiche cerebrali.
Obiettivo
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.
Campo scientifico
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-COG - Consolidator GrantIstituzione ospitante
10117 Berlin
Germania