Optogenetically induced spatiotemporal gamma oscillations and neuronal spiking activity in primate motor cortex

Abstract

Transient gamma-band (40-80 Hz) spatiotemporal patterns are hypothesized to play important roles in cortical function. Here we report the direct observation of gamma oscillations as spatiotemporal waves induced by targeted optogenetic stimulation, recorded by intracortical multichannel extracellular techniques in macaque monkeys during their awake resting states. Microelectrode arrays integrating an optical fiber at their center were chronically implanted in primary motor (M1) and ventral premotor (PMv) cortices of two subjects. Targeted brain tissue was transduced with the red-shifted opsin C1V1(T/T). Constant (1-s square pulses) and ramp stimulation induced narrowband gamma oscillations during awake resting states. Recordings across 95 microelectrodes (4 × 4-mm array) enabled us to track the transient gamma spatiotemporal patterns manifested, e.g., as concentric expanding and spiral waves. Gamma oscillations were induced well beyond the light stimulation volume, via network interactions at distal electrode sites, depending on optical power. Despite stimulation-related modulation in spiking rates, neuronal spiking remained highly asynchronous during induced gamma oscillations. In one subject we examined stimulation effects during preparation and execution of a motor task and observed that movement execution largely attenuated optically induced gamma oscillations. Our findings demonstrate that, beyond previously reported induced gamma activity under periodic drive, a prolonged constant stimulus above a certain threshold may carry primate motor cortex network dynamics into gamma oscillations, likely via a Hopf bifurcation. More broadly, the experimental capability in combining microelectrode array recordings and optogenetic stimulation provides an important approach for probing spatiotemporal dynamics in primate cortical networks during various physiological and behavioral conditions.

Optogenetics: 10 years of microbial opsins in neuroscience

“…58) and the nonhuman primate (for example, ref. 59) have also emerged. The capabilities that have come along with the emergence of single-component optogenetics as a standard research tool displaying speed, simplicity and versatility were cited for justifying, in part, the timing and scale of national-scale neuroscience research initiatives launched in 2013, including the BRAIN initia-tive 60 .…”

Metastable brain waves

“…These waves are not merely epiphenomena: For example, they have been reproducibly observed in visual processing [19] -carrying the primary stimulus-evoked response in visual cortex [11,20]; reflecting information flow in response to dynamic natural scenes [21]; encoding directions of moving stimuli [22]; encoding stimulus positions and orientations [23]; underlying bistable perceptual rivalry [24]; reinforcing recent visual experience [25]; and also occur pathologically during visual hallucinations [26]. Waves have been observed in primary motor cortex, where they mediate information transfer during movement preparation [12], can be induced by optogenetic stimulation [27], and reveal the nature of the excitability of neural tissue [28]. They have also been implicated in sensorimotor processing of saccades [29], propagating seizure fronts [30,31], and observed during sleep with a possible role in memory consolidation [4].…”

Forelimb movements evoked by optogenetic stimulation of the macaque motor cortex

“…Despite these remarkable results in rodents, optogenetic stimulation of the sensorimotor cortex in macaque monkeys using ChR2 failed to induce arm and hand movements 13,14 . In another study, although gamma oscillations were induced in the macaque motor cortex by optogenetic stimulation using a ChR2 variant, no clear behavioral modulation was observed 15 . Transduction of enhanced NpHR (eNpHR) into the macaque M1 hand-arm region caused suppression of M1 neuronal activity, but no obvious modulation of reaching and grasping behaviors was found 13,25 .…”

“…Eye movements can be successfully modulated by optogenetic activation or inactivation of the cerebral cortex 8,9,10,11,12 . On the other hand, optogenetic stimulation of the motor cortices in monkeys failed to induce apparent body movements, although it activated or modulated cortical activity 13,14,15 . This may be because opsins were not sufficiently expressed in neurons, and/or lights did not effectively penetrate the monkey brain tissue 13,16 .Inducing movements by optogenetics is a very important next step in non-human primate research.…”