Robotic Patch Clamp Electrophysiological Signal Measurement in Multiple Brain Regions Based on Brain Slice Registration

Patch clamp technique is a ”gold standard” approach to the study of ion channel biophysics and pharmacology. Due to the complexity of the operation and the heavy reliance on the experience of the experimenter, more and more researchers are focusing on patch clamping automation. In manual patch clamping, the operators patch the neurons in the specific brain region by experience, which lacks quantitative indicators of brain region selection. At present, the existing automated patch clamp focuses more on searching and measuring single cells under a high magnification lens, but ignores the localization of different brain regions under a low magnification lens, affecting the efficiency and application of the automated system. Addressing this, a 2D-3D registration method is proposed to register the experimental microscopic image of brain slices onto the brain atlases. This method is then embedded into the patch clamp system for brain region selection and electrophysiological recordings of neurons in multiple brain regions. It is the first time to achieve automated selection of brain regions in patch clamp experiments. The experimental results indicate that brain slice registration and brain region selection completely meet the requirements of the patch clamp experiment. Compared with the original robotic patch clamp process, the total time for the whole-cell patch clamp initialization with the improved process is reduced by 280 seconds, and the efficiency is increased by 42%. Meanwhile, the time for brain region switching is reduced to 1/6 of the original. In the future, this method will be applied to automatic image-guided patch clamp systems. Note to Practitioners—Calibrating the depth of the experimental brain slice in the brain and dividing the distribution of each brain region in the brain slice are the most important preparations for electrophysiological experiments. In this paper, we design 2D-3D registration to establish a method for brain region selection and robotic patch clamping of different brain regions in one brain slice. We have successfully detected the electrophysiological signals of neurons in 3 major brain regions, including the visual region, auditory region, and hippocampus. The experimental results show that the method proposed in this paper is suitable for the existing robotic patch clamp system and greatly improves the degree of automation.