Microelectrode array scaled for human hippocampal slices

Abstract

Objective: Temporal lobe epilepsy (TLE) is characterized by recurrent seizures originating usually from the hippocampus, and approximately one-third of TLE patients remain refractory to pharmacological interventions. Surgical resection offers a potential cure for refractory TLE cases, with approximately 70% achieving seizure freedom. Still, the pathogenesis of TLE remains poorly understood. Electrophysiological characterization of the resected tissue with microelectrode arrays (MEAs) can help reveal the pathogenesis of TLE, but the commercially available MEAs cover only a small part of the hippocampal cross-section. The objective here is to develop a MEA that can cover a significant area of a human hippocampal slice to help understand the electrophysiology of TLE pathogenesis. Methods: The custom MEA, entitled Hippo-MEA, was designed to have 60 round electrodes, each 60 μm in diameter, in an area of 5.6 mm × 5.6 mm. The titanium nitride-coated electrodes were deposited on borosilicate glass using ion beam-assisted e-beam deposition (IBAD) process. Hippo-MEA's sample chamber, named Sample Cup, was designed large enough to hold a human hippocampal slice. Hippocampal samples were obtained from patients undergoing neurosurgical tissue resection for TLE treatment and sliced to 300 μm thick sections for Hippo-MEA recording. Data from the Hippo-MEA were recorded using the commercially available MEA2100-Mini-system. Cellular composition of the recording area was analyzed with immunohistochemistry (IHC). Results: Extracellular action potentials (EAPs) and local field potentials (LFPs) were successfully recorded from acute human hippocampal slices. Activity was mainly localized to the dentate gyrus, whereas the CA regions found sclerotic and gliotic in IHC analysis showed little to no activity. Significance: Hippo-MEA is compatible with a commercially available and widely used data acquisition system and enables recording of EAPs and LFPs across several regions of human hippocampal tissue. This enables Hippo-MEA, in combination with other methods, to help discover the neurophysiological mechanisms of TLE. Plain Language Summary: In some cases of temporal lobe epilepsy (TLE), the only treatment option is to surgically remove a part of the brain, including a structure known as the hippocampus, which is often the source of the electrical epileptic activity. Understanding hippocampal function is important to understanding the reasons behind TLE and designing the surgeries. Microelectrode arrays (MEAs) are a tool for recording the electrical function of tissues. Here we present a new MEA, named Hippo-MEA, that is big enough to measure a cross-section of the human hippocampus.