SUBJECT: Ph.D. Dissertation Defense
BY: Gregory Holst
TIME: Monday, October 24, 2016, 1:00 p.m.
TITLE: In Vivo Serial Patch Clamp Robotics for Cell-Type Identification in the Mouse Visual Cortex
COMMITTEE: Dr. Craig R. Forest, Chair (ME)
Dr. Hongkui Zeng (Allen Institute For Brain Science)
Dr. Edward S. Boyden (Media Lab, MIT)
Dr. Garrett B. Stanley (BME)
Dr. Todd Sulchek (ME)
Dr. Suhasa B. Kodandaramaiah (MD, University of Minnesota)


In 2013, President Obama announced the Brain Initiative to fund the development of new tools for studying the brain and to identify the root causes of nervous system disorders. Our knowledge of the brain is currently limited by our ability to record the dynamic activity of neurons in intact, behaving circuits. Here we show the development of robotics tools to investigate the unique behaviors of neurons in the visual cortex of mice and transform the highly manual art of obtaining patch clamp recordings into a systematic, automated procedure. The patch clamp technique is the gold standard for recording the intracellular electrical activity of individual cells and has the highest resolution and specificity of any other technique. However, the manual methods used to control the position, pressure, and voltage of the glass recording pipette severely limit the throughput and the ability to perform multiple simultaneous recordings in vivo. This work shows the development of automation systems to precisely and repeatably prepare the recording pipette, position it in the brain, establish the recording, and conduct the entire electrophysiological experiment all without requiring the presence of a human operator. The robot has autonomously obtained multiple, consecutive recordings in vivo with the same quality and throughput as a human operator. Robotic hardware and software algorithms enable parallel scaling for increased throughput, systematic operation, and rapid dissemination of challenging techniques. These tools will increase our capacity to rapidly identify new cell-type classification schemes and understand the in vivo function and dysfunction of cells within the nervous system.