Abstracts

Rationale: 2-Dimensional high-density microelectrode array (HD-MEA) systems are advanced tools used in electrophysiological research. These systems use complementary metal-oxide semiconductor (CMOS) technology that can be used to capture epileptiform activity from brain tissue slices with great spatial and temporal accuracy. However, using these systems can be challenging because brain tissue must remain healthy and be properly adhered to the array to get high-quality data. To help researchers leverage this technology, we aim to provide a guide on using HD-MEA systems to record seizure-like activity. We will demonstrate the utility of this technology to record ictal-like activity and argue that this technology can be a powerful new tool in our goal to understand seizure disorders and the neuropathological activity associated with these disorders.


Methods: Acute mouse brain slices were prepared with a vibratome at a depth of 350 μm. The slice containing neocortex and hippocampus is placed on the microelectrode array. A pro-convulsant media, such as 4-AP and 0 Mg²⁺ solutions, is then introduced to the perfusion system to induce seizure-like activity. The frequency, amplitude, and spectral properties of the electrographic seizure data were then analyzed using a graphic user interface (GUI) developed by the lab.

Results: The results generated from our protocol highlight the utility of CMOS HD-MEA technology for epilepsy research that employs ex vivo seizure models. Our experiments using CMOS-HD-MEA systems suggest that the 0 Mg²⁺ paradigm generated stronger electrographic seizure-like activity in neocortical regions compared to the 4AP paradigm. Overall, our results suggest that the 0 Mg²⁺ paradigm is preferable for studying high-frequency data with CMOS-HD-MEA systems, while the 4AP model provides valuable insights into lower frequency bands and general epileptiform discharges. Importantly, both paradigms effectively produce high-quality tonic-clonic-like seizures using our protocol.

Conclusions: The unique protocol we have developed with the HD-MEAs provides an innovative method for studying ictogenesis and seizure propagation using ex vivo models in unprecedented spatial and temporal resolution. This research demonstrates that CMOS-HD-MEA technology can be used to elucidate the spatiotemporal dynamics of seizure-like activity in ex vivo models when proper methodology is utilized, significantly advancing techniques in empirical epilepsy research.


Funding: Funding was provided by Brigham Young University College of Life Sciences, Brigham Young University College of Physical and Mathematical Sciences, AES/EF Junior Investigation Award.