A Large-Scale Interface for Optogenetic Stimulation and Recording in Nonhuman Primates

Abstract

While optogenetics offers great potential for linking brain function and behavior in nonhuman primates, taking full advantage of that potential will require stable access for optical stimulation and concurrent monitoring of neural activity. Here we present a practical, stable interface for stimulation and recording of large-scale cortical circuits. To obtain optogenetic expression across a broad region, here spanning primary somatosensory (S1) and motor (M1) cortices, we used convection-enhanced delivery of the viral vector, with online guidance from MRI. To record neural activity across this region, we used a custom micro-electrocorticographic (μECoG) array designed to minimally attenuate optical stimuli. Lastly, we demonstrated the use of this interface to measure spatiotemporal responses to optical stimulation across M1 and S1. This interface offers a powerful tool for studying circuit dynamics and connectivity across cortical areas, for long-term studies of neuromodulation and targeted cortical plasticity, and for linking these to behavior.

Primate optogenetics: Progress and prognosis

“…M1 is reciprocally connected with the primary somatosensory cortex (S1). To investigate communication between these areas, Yazdan-Shahmorad et al (42) expressed C1V1 in areas M1 and S1 of macaques, delivered optical stimulation through artificial dura, and measured neural activity using electrocorticography. Optical stimulation of the 2 areas simultaneously or in isolation strengthened the functional connectivity between them (43).…”

At Light Speed: Advances in Optogenetic Systems for Regulating Cell Signaling and Behavior

“…As with in vitro methods, spatial precision can be conveyed with a spatial light modulator (107) or a scanning laser (108). Such methods can also be extended to the mammalian brain, where window craniotomies in live animal brains give light access to the superficial layers of the cortex from a microscope (widefield or point-scanning) (109, 110), mounted LED (111), or fiberoptic cable (97, 112, 113). These techniques are further enhanced by engineered red-shifted variants of rhodopsins (114, 115) and rhodopsin two-photon excitation (116, 117) to allow deeper tissue penetration.…”

Long-term all-optical interrogation of cortical neurons in awake-behaving non-human primates

“…Channelrhodopsin-2 (ChR2) is a commonly used optogenetic actuator for NHPs, though it often requires high laser power to evoke neuronal and behavioral responses [14][15][16][17]21 . The high conductance and red-shifted absorption spectrum of C1V1 makes it a preferable choice 12,34,38,39 . This is especially true for AOI experiments, since C1V1's excitation spectrum is well separated from that of GCaMPs 31,32 .…”