Functional ultrasound imaging of the spreading activity following optogenetic stimulation of the rat visual cortex

Abstract

Optogenetic stimulation of the primary visual cortex (V1) is a promising therapy for sight restoration, but it remains unclear what total cerebral volume is activated after surface stimulation. In this study, we expressed the red-shifted opsin ChrimsonR in excitatory neurons within V1 in rats, and used the fine spatial resolution provided by functional ultrasound imaging (fUS) over the whole depth of the brain to investigate the brain response to focal surface stimulation. We observed optogenetic activation of a high proportion of the volume of V1. Extracellular recordings confirmed the neuronal origin of this activation. Moreover, neuronal responses were even located in deep layers under conditions of low irradiance, spreading to the LGN and V2, consistent with a normal visual information process. This study paves the way for the use of optogenetics for cortical therapies, and highlights the value of coupling fUS with optogenetics.

Vision Restoration by Optogenetic Therapy and Developments Toward Sonogenetic Therapy

“…Expression of a microbial opsin in the visual cortex was found to activate cortical neurons even in the cortex depth following surface illumination of the brain. 55 – 57 In non-human primates, this cortical activation produced visual saccades toward the corresponding point in the visual field 55 , 56 , 58 and was able to elicit activity in other visual areas as indicated by functional magnetic resonance imaging (fMRI). 58 More subtle changes were described, such as an increased sensitivity to the stimulus orientation, only when the optogenetic stimulation was applied on a column with an orientation selectivity close to that of the stimulus.…”

Neural correlates of blood flow measured by ultrasound

“…fUSI is appealing because it estimates changes in cerebral blood volume with high resolution, resolving spatial features in the order of ~100 μm up to a depth of ~2 cm (Macé et al, 2011). It is thus used to study how the activity of brain regions depends on sensory stimuli, internal state, and behavior, in multiple species including mice (Aydin et al, 2020;Boido et al, 2019;Brunner et al, 2020;Ferrier et al, 2020;Koekkoek et al, 2018;Macé et al, 2018;Sans-Dublanc et al, 2021), rats (Bergel et al, 2018;Bergel et al, 2020;Gesnik et al, 2017;Macé et al, 2011;Osmanski et al, 2014;Provansal et al, 2021;Rahal et al, 2020;Sieu et al, 2015;Urban et al, 2015), marmosets (Zhang et al, 2021), ferrets (Bimbard et al, 2018), and macaques (Blaize et al, 2020;Dizeux et al, 2019). In a small animal like a mouse, fUSI can image the whole brain, yielding measurements that may parallel those obtained in humans with functional magnetic resonance imaging (fMRI).…”