Excitatory/Inhibitory Responses Shape Coherent Neuronal Dynamics Driven by Optogenetic Stimulation in the Primate Brain

Abstract

Coherent neuronal dynamics play an important role in complex cognitive functions. Optogenetic stimulation promises to provide new ways to test the functional significance of coherent neural activity. However, the mechanisms by which optogenetic stimulation drives coherent dynamics remain unclear, especially in the nonhuman primate brain. Here, we perform computational modeling and experiments to study the mechanisms of optogenetic-stimulation-driven coherent neuronal dynamics in three male nonhuman primates. Neural responses arise from stimulation-evoked, temporally dynamic excitatory (E) and inhibitory (I) activity. Spiking activity is more likely to occur during E/I imbalances. Thus the relative difference in the driven E and I responses precisely controls spike timing by forming a brief time interval of increased spiking likelihood. Experimental results agree with parameter-dependent predictions from the computational models. These results demonstrate that optogenetic stimulation driven coherent neuronal dynamics are governed by the temporal properties of E/I activity. Transient imbalances in excitatory and inhibitory activity may provide a general mechanism for generating coherent neuronal dynamics without the need for an oscillatory generator.

Profiling the transcallosal response of rat motor cortex evoked by contralateral optogenetic stimulation of glutamatergic cortical neurons

“…Detailed knowledge about the dose-response properties is critical to the selection of the optimal stimulation parameters and to understanding the evoked neuronal response. A recent study measured locally evoked spiking and LFP activity at the site of cortical optogenetic stimulation in awake, alert non-human primates confirms our conclusion [28]. In that study, the selection of stimulation variables determined the stimulation-evoked, excitatory-inhibitory responses, highlighting the role of in-depth understanding of dose-response relationships in optogenetic stimulation studies.…”

“…The present study significantly extends previous work on optogenetic stimulation of transcallosal projections in rodents. We explored the impact of a various combinations of stimulus intensities and durations on the magnitude of the transcallosally evoked cortical potential, covering the most commonly used stimulation variables [20,28,[45][46][47][48][49][50][51]. We show that the probability to reliably evoke a transcallosal cortical response gradually increased with the intensity and duration of the (which was not certified by peer review) is the author/funder.…”

“…But appropriate use of optogenetic interventions requires detailed knowledge about the stimulusresponse relationship between the stimulation variables and the evoked neuronal response in the contralateral hemisphere. Recent optogenetic studies in rodents and nonhuman primates emphasize that the stimulation induced neuronal activity in the brain, such as the size of the evoked local field potential (LFP) or the change in axonal firing rates, depends on the stimulation variables, such as the stimulation intensity applied or the duration of laser stimulation [25,27,28]. Although the impact of key variables might have been investigated systematically beforehand in many optogenetic stimulation studies, it often remains unclear why a specific set of stimulation variables was used for optogenetic stimulation.…”

Marmosets: a promising model for probing the neural mechanisms underlying complex visual networks such as the frontal–parietal network

“…By exploiting viruses incorporating cell-specific promoters, it has been possible to determine the contribution of different cell types, particularly excitatory and inhibitory cells (Cardin et al 2009;De et al 2020). This is important because computational modelling has suggested that temporally coherent neural activity is driven by windows of neural excitation and inhibition (Shewcraft et al 2020). This opens the door to using optogenetics to probe network dynamics and their cellular origins.…”

Light Up the Brain: The Application of Optogenetics in Cell-Type Specific Dissection of Mouse Brain Circuits

“…Optogenetics has also been used in higher mammals, such as Rhesus monkeys, enabling the causal study of circuits involved in complex behaviors and neurological diseases (Han et al, 2009;Jazayeri et al, 2012;Shewcraft et al, 2020). In the first study that validated the use of optogenetics in non-human primates, Han et al used lentivirus to express ChR2 in the frontal cortex of macaques, and established that viral expression of opsins is safe and can support long-term experiments (Han et al, 2009).…”