Targeted cortical stimulation reveals principles of cortical contextual interactions

Abstract

Cross-orientation suppression is a classic form of contextual normalization in visual cortex, yet the degree to which cortical circuits participate in the normalization computation is unclear. We visualized orientation maps of individual ferrets, and provided patterned optogenetic stimulation to both excitatory and inhibitory cells in orientation columns that either matched or were orthogonal to the preferred visual orientation of neurons recorded with electrodes. When visual or optogenetic stimulation of columns preferring one orientation was combined with optogenetic stimulation of columns preferring the orthogonal orientation, we observed less suppression than when orthogonal stimulation was provided visually, suggesting that cortical circuits do not provide a large fraction of visual cross-orientation suppression. Integration of visual and optogenetic signals was linear when neurons exhibited low firing rates and became sublinear when neurons exhibited higher firing rates. We probed the nature of sublinearities in cortex by examining the influence of optogenetic stimulation of cortical interneurons. We observed a range of responses, including evidence for paradoxical responses in which interneuron stimulation caused a decrease in inhibitory firing rate, presumably due to the withdrawal of recurrent excitation. These results are compatible with cortical circuits that exhibit strong recurrent excitation with stabilizing inhibition that provides normalization, albeit normalization that is too weak across columns to account for cross-orientation suppression.

Mechanisms underlying reshuffling of visual responses by optogenetic stimulation in mice and monkeys

“…The response properties of cortical networks to optogenetic inputs we have found here might also be relevant to understanding responses of neurons observed in other conditions. Large numbers of suppressed cells in response to optogenetic activation of pyramidal cells have been reported in experiments using one-photon stimulation in mouse visual cortex (O’Rawe et al, 2022), ferret visual cortex (Wang et al, 2022), and targeted two-photon stimulation of small ensembles in mouse barrel cortex (Dalgleish et al, 2020). Weak changes in mean population activity together with large changes in individual neuronal firing rates also characterize the response of cortex to some modulatory inputs (Sherman and Guillery, 1998), e.g .…”

Mechanisms underlying reshuffling of visual responses by optogenetic stimulation in mice and monkeys

“…The modulation of visual responses by optogenetic stimuli we have described, characterized by large changes in single neuron firing that weakly affect the overall activity of the network, might be relevant to understand responses of neurons observed in other conditions. Large numbers of suppressed cells in response to optogenetic activation of pyramidal cells have been reported in experiments using one-photon stimulation in mouse visual cortex (O'Rawe et al, 2022), ferret visual cortex (Wang et al, 2022), and targeted two-photon stimulation of small ensembles in mouse barrel cortex (Dalgleish et al, 2020).…”

Optogenetic stimulation recruits cortical neurons in a morphology-dependent manner

“…Until recently, longterm optogenetic wide-field manipulations in higher mammals were limited, but now become feasible through implantable stimulator arrays using single-photon-based stimulation (3,4). This advancement opens a path towards a sophisticated interrogation of sensory or motor code in meaningful volumes of cortex (3,(5)(6)(7)(8), as well as development of neuro-prosthetic systems for vision and hearing loss remediation (3,(8)(9)(10). However, these applications require spatially precise stimulation to selectively engage functional cortical representations at a spatial scale of cortical columns (11,12) requiring sub-millimeter precision (13), which in experiments proved challenging due to the spatial spread of stimulation-evoked responses (5,6,8).…”

“…This advancement opens a path towards a sophisticated interrogation of sensory or motor code in meaningful volumes of cortex (3,(5)(6)(7)(8), as well as development of neuro-prosthetic systems for vision and hearing loss remediation (3,(8)(9)(10). However, these applications require spatially precise stimulation to selectively engage functional cortical representations at a spatial scale of cortical columns (11,12) requiring sub-millimeter precision (13), which in experiments proved challenging due to the spatial spread of stimulation-evoked responses (5,6,8). The observed spatial spreading and complex distribution of responses to stimulation may be attributed to propagation and transformation of the stimulation-evoked responses in the network (14)(15)(16)(17).…”