ELECTROPHYSIOLOGICAL BIOMARKERS OF FOCAL CORTICAL DYSPLASIA (FCD) RECORDED USING NEUROPIXELS PROBES IN AWAKE HEAD-FIXED MICE

Focal cortical dysplasia type II (FCDII) is a brain disorder characterized by abnormal cortical development and dysplastic neurons, often leading to drug-resistant epilepsy and associated cognitive and behavioral issues. Despite the availability of rodent models of FCDII, the mechanisms underlying seizure initiation and propagation remain unclear. This project aims to investigate the recruitment of neurons across multiple brain areas in awake, head-fixed mice using Neuropixels probes, focusing on interictal epileptic discharges (IEDs) and seizures to identify neural targets for potential gene therapies. A well-established FCDII mouse model was used, generated by in utero electroporation of neuronal progenitors with a plasmid containing a constitutively active version of the Ras homolog enriched in brain (RHEB) gene together with a tdTomato fluorescent reporter. Control mice were generated by electroporating only the tdTomato reporter. Post-hoc analysis was performed after staining the probes. In all mice, we successfully recorded high-density local field potentials (LFPs) and single-unit activity from neurons on two separate recording days. Interictal discharges (IEDs) and seizures were identified in the epileptic mice and localized to specific regions of the brain. Neurons in the dysplastic region were distinguished from those in non-dysplastic region based on their spike morphology and firing patterns. This study demonstrates the successful use of Neuropixels probes to record pathological activity in FCDII mice. The ability to spatially map the initiation and spread of these activities could provide valuable insights to identify targets for anti-epileptic gene therapies.