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Published October 16, 2013 | Published
Journal Article Open

Saccade Modulation by Optical and Electrical Stimulation in the Macaque Frontal Eye Field

Abstract

Recent studies have demonstrated that strong neural modulations can be evoked with optogenetic stimulation in macaque motor cortex without observing any evoked movements (Han et al., 2009, 2011; Diester et al., 2011). It remains unclear why such perturbations do not generate movements and if conditions exist under which they may evoke movements. In this study, we examine the effects of five optogenetic constructs in the macaque frontal eye field and use electrical microstimulation to assess whether optical perturbation of the local network leads to observable motor changes during optical, electrical, and combined stimulation. We report a significant increase in the probability of evoking saccadic eye movements when low current electrical stimulation is coupled to optical stimulation compared with when electrical stimulation is used alone. Experiments combining channelrhodopsin 2 (ChR2) and electrical stimulation with simultaneous fMRI revealed no discernible fMRI activity at the electrode tip with optical stimulation but strong activity with electrical stimulation. Our findings suggest that stimulation with current ChR2 optogenetic constructs generates subthreshold activity that contributes to the initiation of movements but, in most cases, is not sufficient to evoke a motor response.

Additional Information

© 2013 The Authors. Received June 24, 2013. Revision received September 9, 2013. Accepted September 14, 2013. Author contributions: S.O. and D.Y.T. designed research; S.O. performed research; S.O., P.G., and N.S. contributed unpublished reagents/analytic tools; S.O. analyzed data; S.O. and D.Y.T. wrote the paper. This work was supported by National Institute of Health Grant 1R01EY019702, the Della Martin Foundation, and a Searle Scholar Award (D.Y.T.). We thank Sebastian Moeller for his assistance in preparing the electrical microstimulation experiments, David Anderson for using his confocal setup to image histological slices, Ilka Diester for her continuing support with setting up viral injections, Karl Deisseroth for the hSyn–ChR2(H134R)– eYFP, hSyn–ChR2(E123A)– eYFP, CaMKII–ChR2(E123A)–mCherry and hSyn– eNpHR3.0–eYFP plasmids, and Ed Boyden for the CAG–Arch– eGFP plasmid. The authors declare no competing financial interests.

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