WP 2 | Dysfunctional communication in the epileptic brain

Objectives

O2.1 Identification of pathways involved in early epileptogenesis and ictogenesis
O2.2 Analysis of secondarily generalized seizures in TLE and genetically determined seizures in AE
O2.3 Confirmation of results obtained in animal models in human surgical specimen

WP2 will comprise the comparative analysis of Ca²⁺-based signalling of neuron-glia communication in models of chemical-induced epileptiform activity as well as in genetic mouse and rat models of epilepsy. Analyses of the temporal and spatial relationship between epileptiform activity patterns and glial Ca²⁺ signals in correlation to neuronal network activity, and the impact of gliotransmitter release on the different patterns of neuronal hyperactivity, will be performed. The results will clarify to what extent a dysregulation of neuron-glia signalling contributes to seizure onset, maintenance, and cessation. Ultimately, the unique possibility to obtain living hippocampal specimens from epilepsy patients will be exploited to afford functional analyses of neuron-glia interactions in human brain tissue. A fully equipped research set-up will be provided to combine the different expertise of the consortium with the aim to investigate in human tissue the mechanisms of neuron-glia interactions that had been established and verified in animal models.

Tasks (and involved participants)

T2.1 Analysis of astrocyte dysfunction in early epileptogenesis (UKB, CdF, OUS)
T2.2 Analysis of astrocyte dysfunction during ictogenesis (CNR, UKB, FINCB)
T2.3 Analysis of astrocyte dysfunction during generalized seizures in TLE and AE (USAAR, CU, NPI, CdF, AU)
T2.4 Comparison of results obtained in animal models with human surgical specimen (UKB, FINCB, AMC)

Deliverables 

D2.1 Description of molecular and cellular properties defining neuron-glia network activities during the early phase of epileptogenesis and ictal seizures in slices and in vivo (Mo 18);
D2.2 Quantitative description of GABAergic neuron-glia communication in animal models of TLE and AE (Mo 24);
D2.3 Catalogue of miRNA-related expression profiles in human astrocytes obtained from patient material (Mo 18)