Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, United States; Laboratory for Neuroengineering, Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, United States
Ming-fai Fong
Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, United States; Laboratory for Neuroengineering, Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, United States; Department of Physiology, Emory University School of Medicine, Atlanta, United States
Daniel C Millard
Laboratory for Neuroengineering, Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, United States; Axion Biosystems, Atlanta, United States
Clarissa J Whitmire
Laboratory for Neuroengineering, Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, United States
Garrett B Stanley
Laboratory for Neuroengineering, Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, United States
Steve M Potter
Laboratory for Neuroengineering, Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, United States
Optogenetic techniques enable precise excitation and inhibition of firing in specified neuronal populations and artifact-free recording of firing activity. Several studies have suggested that optical stimulation provides the precision and dynamic range requisite for closed-loop neuronal control, but no approach yet permits feedback control of neuronal firing. Here we present the ‘optoclamp’, a feedback control technology that provides continuous, real-time adjustments of bidirectional optical stimulation in order to lock spiking activity at specified targets over timescales ranging from seconds to days. We demonstrate how this system can be used to decouple neuronal firing levels from ongoing changes in network excitability due to multi-hour periods of glutamatergic or GABAergic neurotransmission blockade in vitro as well as impinging vibrissal sensory drive in vivo. This technology enables continuous, precise optical control of firing in neuronal populations in order to disentangle causally related variables of circuit activation in a physiologically and ethologically relevant manner.
