Closed-loop Optogenetic Disruption of Interictal Epileptiform Discharges in the Dentate Gyrus to Target Cognitive Dysfunction in Neurodegenerative Disease.

• Applicant: Dr. Elisabeth Heynold
• Subject Area: Molecular and Cellular Neurology and Neuropathology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 536202420

The hippocampus deep in the temporal lobe of the brain is a key processing unit for conscious memories. Interictal epileptiform discharges (IEDs) disrupt the encoding and retrieval of memories in epilepsy patients, even in the absence of seizures. IEDs also occur in various other neurologic diseases, including Alzheimer’s dementia, traumatic brain injury, autism, ADHD and many more. In the here proposed project we plan to investigate IEDs in detail, we want to understand their propagation through the hippocampus and trial an innovative therapeutic approach.In this project we will use a mouse model of Alzheimer’s disease to examine IEDs with chronically implanted, high-density electrodes and a technique called optogenetics, which allows us to manipulate the activity of selected neurons with light. The project's first aim is to investigate how IEDs travel through the hippocampus. We are especially interested in the role of inhibitory neurons in a substructure of the hippocampus, the dentate gyrus. Our hypothesis is that the dentate gyrus acts as gate for physiological but also pathological signals arriving to the hippocampus and that the concerted activity of one subclass of these inhibitory cells, which express the neuropeptide somatostatin, can stop IEDs or let them pass. The second aim of the project is to detect IEDs in real time and stop them by stimulating these inhibitory brain cells ‘on-demand’ in a closed loop fashion but let simultaneously occurring memory-bearing signals pass uninterrupted. The third and final aim of the project is to investigate the effect of this closed loop stimulation on memory tasks. We thereby want to pave the way for new memory-improving neurostimulation treatments in patients with neurocognitive disorders.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Professor Dr. Gyorgy Buzsaki, Ph.D.