The role of the locus coeruleus noradrenergic system in seizures and epilepsy

Epilepsy is a common neurological disorder affecting upwards of 1% of the population, of which one in three patients do not respond to available antiepileptic medication. This can be at least partially attributed to a poor understanding of mechanisms underlying seizures and epilepsy. In recent experiments, my colleagues and I have gathered compelling evidence that hippocampal seizures are associated with a temporary strong release of noradrenaline in rodent seizure models. Noradrenaline is an endogenous modulator known to play an important role in regulation of excitability and synaptic plasticity. In this project, it is hypothesized that release of noradrenaline in relation to seizures promotes pathological excitability and plasticity thus playing an essential role in driving epileptic seizure activity and in the formation of seizure networks during epileptogenesis. Investigating these hypotheses is enabled through 1) access to novel chemo- and optogenetic tools for precision modulation of the locus coeruleus, 2) access to means of quantifying noradrenaline concentrations in relevant brain areas with subsecond temporal precision, and 3) decades of experience with relevant rodent seizure and epilepsy models, presenting an unique opportunity to make important progress in the understanding of seizure and epilepsy pathophysiology.