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HEIndividual fellowship2023–2025

EpiNeuron · Tracing human cortical neurons involved in epileptic processes at multiple scales

Horizon Europe — Marie Skłodowska-Curie Actions

Duration
2023-09-01 → 2025-08-31
EU contribution
€195,915
Participants
1
Scheme
HORIZON-TMA-MSCA-PF-EF

Lines connect the coordinator with its partners.

Results in brief

Tracing human cortical neurons involved in epileptic processes at multiple scales

Epilepsy affects more than 50 million people worldwide, and about one-third of patients do not respond to medication. The causes of uncontrolled seizures lie in the abnormal activity of specific neurons, yet the detailed behaviour of these cells in the human brain is still largely unknown. Most available knowledge comes from animal experiments, which differ from human neurophysiology in key aspects such as neuronal size, connectivity, and chemical environment. The EpiNeuron project aimed to bridge this knowledge gap by directly studying the electrical activity of neurons in patients undergoing pre-surgical assessment for drug-resistant epilepsy. Using microelectrodes implanted during surgery, the project recorded neuronal firing at high temporal resolution and compared these findings with data obtained from the same patients’ brain tissue after surgery. The ultimate goal was to identify how different types of neurons - particularly excitatory principal cells and inhibitory interneurons - contribute to epileptogenic processes. By combining in vivo and in vitro approaches, the project sought to determine which neuronal properties are intrinsic and which depend on the surrounding network. This knowledge is essential for understanding epileptogenic mechanisms and, in the longer term, for developing more targeted therapeutic strategies.

Data: CORDIS, © European Union

Project objective

Epilepsy is one of the most common chronic neurological diseases in humans, affecting 50 million people worldwide. This brain disorder is characterised by hypersynchronous neural activity resulting in seizures. Abnormal recruitment of cells induces unusual behaviour, sensations or loss of awareness. Epilepsy has a substantial economic effect on health care needs or the loss of productivity in work.Investigating the role of different neuron types in generating pathological activities is essential for identifying what makes a brain region predisposed to generate epileptic events. Most information regarding the properties of neuronal circuits during epileptic activity comes from animal models. However, recent studies have shown substantial differences when comparing human tissue to animals and epilepsy models to disease. I aim to utilise a unique multilevel approach to follow how neurons are recruited into epileptic events and categorise them at an unprecedented level of detail in human epileptic patients. I plan to analyse cellular activity in recordings obtained in vivo and characterise human cortical neurons in vitro with simultaneous intra- and extracellular electrophysiology completed with post hoc histology. This will be the first study examining neuronal behaviour and subtypes in the same epileptic patients, both in vivo (before surgery) and in vitro (after surgery). This innovative approach will provide valuable information on the role of the different neuron types in the generation of epileptiform activity.The fundamental knowledge of the cellular mechanisms of epileptic events specific to humans could help us understand the human disease deeply and thus achieve a significant breakthrough in epilepsy treatment. Enhancement in the diagnostics and cure of epilepsy would considerably decrease the cost of medical care and promise an invaluable improvement in the quality of life on the individual level.

Original text from CORDIS.

Participants

  • INSTITUT DU CERVEAU ET DE LA MOELLE EPINIERE · ParisCoordinatorFrance

Links

Data: CORDIS, © European Union