Propagation measurement between brain regions in acute brain slice using CMOS-MEA

<p>[Introduction] Brain disease and drug toxicity are often caused by transmission disorder between brain regions. Drug discovery in the central nervous system also is aimed at improving transmission disorder. A method to measure the action potential (AP) propagation between brain regions in detail is effective for drug efficacy and toxicity assessment. However, detection of AP propagation in detail between brain regions requires the measurement device with high spatiotemporal resolution. In this research, we attempted to detect the propagation pattern between brain regions and the change of pattern by drug administration using CMOS-Microelectrode Array(MEA), which has over 10,000 electrodes with an electrode pitch 11.72μm.</p><p></p><p>[Methods] The brain slices (300μm) were acutely isolated from adult male C57/BL6NCrSlc mice aged 6-7 weeks and placed in oxygenated (95% O2 and 5% CO2), ice-cold artificial cerebrospinal fluid (ACSF). Spontaneous activities in brain slice were recorded with CMOS-MEA chip (Sony Semiconductor Solutions Corporation). 4-aminopyridine (4-AP) 10 μM and kainic acid (KA) 1 μM were administered to examine the change in propagation pattern due to drug administration, respectively.</p><p></p><p>[Results] Detailed pattern of AP propagation between DG, CA1, CA2, and CA3 regions in hippocampus were detected in convulsants administration. Interestingly, AP propagation between the hippocampus and the cerebral cortex was also measured. This is a feature of our CMOS-MEA, which has a large measurement area that can detect not only the hippocampus region but also other areas at the same time. 4-AP and KA increased the number of synchronous burst firings, but the AP propagation pattern was different. </p><p></p><p>[Conclusion] Using CMOS-MEA measurement method, we detected AP propagation pattern between the brain slice regions, and found that the propagation pattern was different depending on mechanisms of action of drugs. This CMOS-MEA measurement method combined with brain slice is expected to be a new drug efficacy and toxicity assessment method based on the propagation pattern between brain regions.</p>