Fast and reversible neural inactivation in macaque cortex by optogenetic stimulation of GABAergic neurons

Abstract

<jats:p>Optogenetic techniques for neural inactivation are valuable for linking neural activity to behavior but they have serious limitations in macaques. To achieve powerful and temporally precise neural inactivation, we used an adeno-associated viral (AAV) vector carrying the channelrhodopsin-2 gene under the control of a Dlx5/6 enhancer, which restricts expression to GABAergic neurons. We tested this approach in the primary visual cortex, an area where neural inactivation leads to interpretable behavioral deficits. Optical stimulation modulated spiking activity and reduced visual sensitivity profoundly in the region of space represented by the stimulated neurons. Rebound firing, which can have unwanted effects on neural circuits following inactivation, was not observed, and the efficacy of the optogenetic manipulation on behavior was maintained across &gt;1000 trials. We conclude that this inhibitory cell-type-specific optogenetic approach is a powerful and spatiotemporally precise neural inactivation tool with broad utility for probing the functional contributions of cortical activity in macaques.</jats:p>

Non-linear dimensionality reduction on extracellular waveforms reveals cell type diversity in premotor cortex

“…NHP optogenetics is slowly advancing and efforts in many research groups around the world are producing new methods for in vivo optogenetics ( Tremblay et al, 2020 ). We expect future experiments using the promising new mDlx ( De et al, 2020 ) and h56d ( Mehta et al, 2019 ) promoter sequences to selectively opto-tag inhibitory neurons or PV + neurons directly ( Vormstein-Schneider et al, 2020 ) will greatly benefit validation of these derived cell classes. Finally, WaveMAP ’s ability to find clusters of putative biological relevance using waveform shape alone encourages its application in settings where ground truth evaluation is particularly difficult to obtain such as in the human brain ( Paulk et al, 2021 ).…”

Combining Brain Perturbation and Neuroimaging in Non-human Primates

“…Over the past few years, important progress has been made in optogenetic targeting and electrophysiological assessment of specific cell types. Examples include the successful targeting and control of neurons in the koniocellular visual lateral geniculate nucleus pathway (Klein et al, 2016), Purkinje cells in the cerebellar vermis (El-Shamayleh et al, 2017), GABA-ergic interneurons in cortex (De et al, 2020;Dimidschstein et al, 2016), dopaminergic neurons of the midbrain (Stauffer et al, 2016), feedforward and feedback connections between motor thalamus and cortex (Galvan et al, 2016;Yazdan-Shahmorad et al, 2018b), transcortical connections between somatosensory and motor cortex (Yazdan-Shahmorad et al, 2018a), saccade-related projections from FEF to SC (Inoue et al, 2015), ocular dominance and orientation columns in V1 (Chernov et al, 2018), and feedback projections from V2 to V1 (Nurminen et al, 2018). Considerable progress has been made to assess the effect of optogenetic stimulation on cellular activity using electrophysiological methods, and even though optogenetically induced alterations of behavior in NHPs are still sparse, consistent progress is also being made in identifying the circuit-level mechanisms underlying sensation, cognition and motor behavior (reviewed in (El-Shamayleh and Horwitz, 2019;Galvan et al, 2017).…”

Non-linear Dimensionality Reduction on Extracellular Waveforms Reveals Cell Type Diversity in Premotor Cortex

“…NHP optogenetics is slowly advancing and efforts in many research groups around the world are producing new methods for in vivo optogenetics 121 . We expect future experiments using the promising new mDlx 122 and h56d 123 promoter sequences to selectively opto-tag inhibitory neurons or PV + neurons directly 124 will greatly benefit validation of these derived cell classes.…”