Media Lab, Massachusetts Institute of Technology, Cambridge, United States; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, United States; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States; G.W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, United States
Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, United States; Picower Institute for Memory and Learning, Massachusetts Institute of Technology, Cambridge, United States
Gregory L Holst
G.W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, United States
Annabelle C Singer
Media Lab, Massachusetts Institute of Technology, Cambridge, United States; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, United States
Department of Biomedical Engineering, Boston University, Boston, United States
Emery N Brown
Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, United States; Picower Institute for Memory and Learning, Massachusetts Institute of Technology, Cambridge, United States; Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, United States
Edward S Boyden
Media Lab, Massachusetts Institute of Technology, Cambridge, United States; McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, United States; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States
The activities of groups of neurons in a circuit or brain region are important for neuronal computations that contribute to behaviors and disease states. Traditional extracellular recordings have been powerful and scalable, but much less is known about the intracellular processes that lead to spiking activity. We present a robotic system, the multipatcher, capable of automatically obtaining blind whole-cell patch clamp recordings from multiple neurons simultaneously. The multipatcher significantly extends automated patch clamping, or 'autopatching’, to guide four interacting electrodes in a coordinated fashion, avoiding mechanical coupling in the brain. We demonstrate its performance in the cortex of anesthetized and awake mice. A multipatcher with four electrodes took an average of 10 min to obtain dual or triple recordings in 29% of trials in anesthetized mice, and in 18% of the trials in awake mice, thus illustrating practical yield and throughput to obtain multiple, simultaneous whole-cell recordings in vivo.