Optogenetics is a neuromodulation technique which offers a targeted way to modulate neuronal activity using light to control specific neuron populations with high temporal and spatial precision. Light-sensitive microbial proteins, called opsins, are introduced into selected neurons to control their activity with millisecond precision. By combining genetic targeting with optical stimulation, it allows highly specific activation or silencing of defined cell populations within epileptic circuits. At the same time, it enables studies into the neuronal dynamics that underlie pathological activity and how these can be modulated to reveal new therapeutic insights. Insights gained from this approach help guide the development of more efficient and selective treatment strategies.
This is an illustration of an EEG-signal with an epileptic seizure recorded in a preclinical epilepsy mouse model. The seizure is automatically detected, followed by pulsed illumination which suppresses the seizure by suppressing the neurons in the epileptic source.
Inhibitory opsins
For seizure control, inhibitory opsins can be expressed in excitatory hippocampal neurons so that light rapidly suppresses pathological firing. Researcher at 4BRAIN showed that WiChR opsins mediate potent seizure suppression when optical stimulation is performed in the intrahippocampal kainic acid model (IHKA) of temporal lobe epilepsy.
Closed-loop device
In a closed-loop approach, an implanted device continuously records hippocampal activity, detects seizure onset in real time, and immediately triggers light delivery through an optrode. In the IHKA model, such a minimalist embedded system using onboard EEG processing and blue-light stimulation was able to significantly shorten seizures after detection, supporting the feasibility of responsive optogenetic therapy.
At 4Brain, we combine optogenetic manipulation with electrophysiology, histology, and behavioral analyses to build a detailed picture of the mechanisms underlying seizure activity and how these can be used to develop minimally invasive treatment methods.
One of the projects at our lab investigated both this closed-loop system and alternative probe designs for optogenetic neurostimulation. Interested to know more? Read our publications!
Parys A. et al. (2026): Radiopaque coating for improved implantability and in vivo imaging of neural probes.
Pazzaglia F. et al. (2025): Biocompatible, low-loss waveguides for optical neurostimulation.
Lasure S. et al. (2025): Embedded system for responsive optogenetic control of spontaneous seizures in a preclinical temporal lobe epilepsy model.
Researcher(s) involved in this research line:
-
Robrecht Raedt
Professor Robrecht Raedt, PhD, is leading the preclinical 4Brain research lab, with a main focus on new treatment techniques as a treatment for various neuropsychiatric disorders (epilepsy, stroke, multiple sclerosis, glioblastoma).
-
-
-
