Optical intrinsic signal imaging with optogenetics reveals functional cortico-cortical connectivity at the columnar level in living macaques

Abstract

Despite extensive research on primate cognitive function, understanding how anatomical connectivity at a neural circuit level relates to information transformation across different cortical areas remains primitive. New technology is needed to visualize inter-areal anatomical connectivity in living monkeys and to tie this directly to neurophysiological function. Here, we developed a novel method to investigate this structure-function relationship, by combining optical intrinsic signal imaging (OISI) with optogenetic stimulation in living monkeys (opto-OISI). The method involves expressing channelrhodophsin-2 in one area (source) followed by optical imaging of optogenetic activations in the other area (target). We successfully demonstrated the potential of the method with interhemispheric columnar projection patterns between V1/V2 border regions. Unlike the combination of optogenetics and functional magnetic resonance imaging (opto-fMRI), opto-OISI has the advantage of enabling us to detect responses of small clusters of neurons, even if the clusters are sparsely distributed. We suggest that opto-OISI can be a powerful approach to understanding cognitive function at the neural circuit level, directly linking inter-areal circuitry to fine-scale structure and function.

Using rAAV2-retro in rhesus macaques: Promise and caveats for circuit manipulation

“…Until recently, rAAVs produced limited retrograde transport (Aschauer et al, 2013;Castle et al, 2014;Hadaczek et al, 2016;Masamizu et al, 2011;McFarland et al, 2009;Salegio et al, 2013;Taymans et al, 2007;Towne et al, 2010). In NHP opto-and chemogenetics studies, AAVs primarily have been used to manipulate neural activity local to the injection site (Acker et al, 2016;Afraz et al, 2015;Cavanaugh et al, 2012;Dai et al, 2014;El-Shamayleh et al, 2017;Fetsch et al, 2018;Grayson et al, 2016;Ju et al, 2018;Klein et al, 2016;Lu et al, 2015;May et al, 2014;Nagai et al, 2016;Nakamichi et al, 2019;Stauffer et al, 2016;Tamura et al, 2017;Upright et al, 2018;Yazdan-Shahmorad et al, 2016). However, a new rAAV variant-rAAV2-retro-developed through in vivo directed evolution (Tervo et al, 2016) has gained recent popularity because of its highly efficient retrograde transport in rodents (Birdsong et al, 2019;Hong and Heo, 2020).…”

Cerebro-cerebellar interactions in nonhuman primates examined by optogenetic functional magnetic resonance imaging

“…By contrast, the activation of remote brain regions through polysynaptic routes by opto-ICMS in macaques has been unsuccessful. For example, previous studies showed that optogenetic stimulation of the primary visual cortex (V1) evoked activities only in V1 and the areas directly connected to V1 ( Nakamichi et al. 2019 ; Ortiz-Rios et al.…”

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

“…Galvan et al expressed ChR2 in the primary motor cortex of macaque monkeys and optogenetically activated the terminals of the corticothalamic projection from the motor cortex, revealing that this projection pathway plays a modulatory role in the thalamus (Galvan et al, 2016). These studies in non-human primates demonstrate the wider applicability of optogenetics for circuit and behavior analysis with both projection (Inoue et al, 2015;Galvan et al, 2016) and cell-type specificity (Han et al, 2009;Jazayeri et al, 2012;Klein et al, 2016;Nakamichi et al, 2019).…”