In medial temporal lobe epilepsy?a common form of epilepsy that affects roughly one million people in the United States alone?seizures often become resistant to anti-epileptic drugs, making surgical resection of the hippocampus the only available treatment option. For successful surgical treatment, it is critical to determine the seizure onset zone and to resect the tissue precisely. However, there is no current diagnostic method available for clearly identifying the seizure onset zone. High frequency oscillations (HFOs), observed via electroencephalograms (EEG), have been proposed as a biomarker for epilepsy and as a potential tool for determining the seizure onset zone. Understanding the cellular mechanisms of HFO generation is important in establishing HFOs as a biomarker and potentially can improve both diagnostics and surgical precision. No single technology can achieve the spatio-temporal resolution required for investigating the correlation between individual cellular activity and network oscillations. Only when integrating multiple approaches can we begin to accomplish this objective. Recently, we demonstrated that a transparent microelectrode made of graphene can record electrical activity and simultaneously capture individual cellular activity via calcium imaging. The application of this technology to in vivo chronic recordings is beneficial for understanding the cellular basis of neuronal oscillations. To facilitate technological innovation, we set two biologically important milestones: (1) recording hippocampal sharp wave-ripples (a type of normal HFOs) in awake-behaving normal mice and simultaneously imaging calcium transients from hundreds of neurons, and (2) recording HFOs in mice models of epilepsy to elucidate the cellular origin of HFOs. We hypothesize that a group of cells, or a cellular assembly, generates HFOs that can be detected by a graphene electrode located near the cell assembly. The proposed work will provide an important new tool for studying cell assemblies and network oscillations and provide the cellular basis of the HFOs' generation. The electrode/cannula assembly developed here can be applied in other laboratories and can be combined with a miniaturized fluorescence microscope on freely moving animals. Thus, this technology development is vital for the broader neuroscience community.
In temporal lobe epilepsy, seizures are often becoming resistant to anti-epileptic drugs and surgical resection is an important treatment option. High frequency oscillations (HFOs) observed in electroencephalograms can potentially be used to determine the seizure onset zone. This project will apply a new technology to understanding the cellular mechanisms of HFO generation in biological model of epilepsy.
