Closed-loop neural control with optogenetics and MEAs
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1
Georgia Institute of Technology and Emory University School of Medicine, Laboratory for Neuroengineering, Department of Biomedical Engineering, United States
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2
Emory University School of Medicine, Department of Physiology, United States
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3
Axion Biosystems, Applications Development, United States
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4
Massachusetts Institute of Technology, Picower Institute for Learning and Memory, United States
For 16 years (1999-2015), my labs at Caltech and Georgia Tech developed closed-loop hybrid systems incorporating MEAs and living neural tissue. In some cases, cultured cortical networks were used to control robots or simulated animals, with distributed MEA electrical stimulation serving as a modulation signal, as a training signal, and as artificial sensory input. In our most recent work, and in collaboration with the labs of Garrett Stanley and Peter Wenner, we developed and tested a closed loop system in which modulatory input was delivered with light that was controlled by the neural activity recorded from MEAs. Optogenetics provides a number of advantages for controlling neural activity, such as high time resolution, cell-type specificity, the ability to excite or inhibit neurons, and freedom from electrical artifacts. By transducing rat cortical cultures with optogenetic constructs, we were able to raise network activity with blue light, and to lower it with yellow light, in a very precise and graduated way. By closing the control loop using the recorded activity from the MEAs upon which the cultures grew (Fig. 1), we could clamp neural activity to any selected value (Fig. 2) with different amounts of blue (excitatory) and yellow (inhibitory) LED light. We call this the Optoclamp (1), and we applied it to the study of homeostatic mechanisms (2) and sensory processing (1) in neural circuits. Using the Optoclamp, we were able to clamp the activity of cortical cultures at various set points, even in the face of perturbations such as drugs or real sensory input, that would tend to reduce or increase firing. This enabled the powerful method of separating previously intertwined variables of synaptic transmission and neural firing. In my farewell talk to the MEA community, I will describe the usefulness of closed-loop control in studying and influencing neural systems. I will outline progress in our lab and elsewhere on hybrid (living + artificial) thinking systems, and describe where I hope this field progresses, with more incorporation of higher-bandwidth technology for both optical and electrical interfaces. I will emphasize the importance of feedback in well-engineered systems with the hope of encouraging more researchers and neuroengineers to incorporate closed-loop control in their hybrid systems. REFERENCES 1. Newman, J. P., Fong, M. F., Millard, D. C., Whitmire, C. J., Stanley, G. B., & Potter, S. M. (2015). Optogenetic feedback control of neural activity. Elife, 4, e07192. 2. Fong, M. F., Newman, J. P., Potter, S. M., & Wenner, P. (2015). Upward synaptic scaling is dependent on neurotransmission rather than spiking.Nature communications, 6. FIGURE CAPTIONS Figure 1. Schematic of closed-loop optical stimulation system. Spiking activity is recorded through the MEA. When the integrated error between the target and measured MEA-wide firing rate becomes positive, a 10-ms current pulse is delivered to an LED. A Kšhler illuminator is used to produce uniformly bright illumination at the cell layer. Reprinted from (2). Figure 2. Proportional-Integral (PI) feedback control to track a changing target rate. (A) Firing rate of detected units. Each row displays the firing rate of a particular unit, encoded by the grey-scale to the right (1 s bins). (B) The average firing rate of the network (black), the target firing rate (red), and the error signal during different control periods. The pre-control firing rate is indicated by a dotted line. (C) Optical control signals delivered by the PI controller during the control epoch. Reprinted from (1).
Acknowledgements
I wish to take this opportunity to thank the MEA community (including the MEA Users group) for all their support, collaboration, and friendship over the years. I also wish to thank the many others in my lab and elsewhere who created the foundations upon which this work was built. I thank the National Institutes of Health for funding this research, via grant R01NS079757. I thank Karl Deisseroth and Ed Boyden for their sharing of optogenetic constructs. These studies were performed in strict accordance with the National Research Council’s Guide for the care and use of laboratory animals using protocols approved by the Georgia Tech IACUC.
Keywords:
Feedback,
optogenetics,
closed-loop,
animat,
Hybrot
Conference:
MEA Meeting 2016 |
10th International Meeting on Substrate-Integrated Electrode Arrays, Reutlingen, Germany, 28 Jun - 1 Jul, 2016.
Presentation Type:
oral
Topic:
MEA Meeting 2016
Citation:
Potter
SM,
Wenner
P,
Millard
DC,
Whitmire
CJ,
Stanley
GB,
Fong
M and
Newman
JP
(2016). Closed-loop neural control with optogenetics and MEAs.
Front. Neurosci.
Conference Abstract:
MEA Meeting 2016 |
10th International Meeting on Substrate-Integrated Electrode Arrays.
doi: 10.3389/conf.fnins.2016.93.00135
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Received:
12 Jul 2016;
Published Online:
13 Jul 2016.
*
Correspondence:
Dr. Steve M Potter, Georgia Institute of Technology and Emory University School of Medicine, Laboratory for Neuroengineering, Department of Biomedical Engineering, Atlanta, United States, stevepwork@gmail.com