In vivo optogenetic stimulation of the primate retina activates the visual cortex after long-term transduction.
Ontology highlight
ABSTRACT:
SUBMITTER: Chaffiol A
PROVIDER: S-EPMC8671818 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:In primates, visual perception is mediated by brain circuits composed of submillimeter nodes linked together in specific networks that process different types of information, such as eye specificity and contour orientation. We hypothesized that optogenetic stimulation targeted to cortical nodes could selectively activate such cortical networks. We used viral transfection methods to confer light sensitivity to neurons in monkey primary visual cortex. Using intrinsic signal optical imaging and single-unit electrophysiology to assess effects of targeted optogenetic stimulation, we found that (i) optogenetic stimulation of single ocular dominance columns (eye-specific nodes) revealed preferential activation of nearby same-eye columns but not opposite-eye columns, and (ii) optogenetic stimulation of single orientation domains increased visual response of matching orientation domains and relatively suppressed nonmatching orientation selectivity. These findings demonstrate that optical stimulation of single nodes leads to modulation of functionally specific cortical networks related to underlying neural architecture.
| S-EPMC6187135 | biostudies-literature
Project description:Because aberrant network-level functional connectivity underlies a variety of neural disorders, the ability to induce targeted functional reorganization would be a profound development toward therapies for neural disorders. Brain stimulation has been shown to induce large-scale network-wide functional connectivity changes (FCC), but the mapping from stimulation to the induced changes is unclear. Here, we develop a model which jointly considers the stimulation protocol and the cortical network structure to accurately predict network-wide FCC in response to optogenetic stimulation of non-human primate primary sensorimotor cortex. We observe that the network structure has a much stronger effect than the stimulation protocol on the resulting FCC. We also observe that the mappings from these input features to the FCC diverge over frequency bands and successive stimulations. Our framework represents a paradigm shift for targeted neural stimulation and can be used to interrogate, improve, and develop stimulation-based interventions for neural disorders.
| S-EPMC9095749 | biostudies-literature
Project description:Astrocytes play important roles in synaptic transmission and plasticity. Despite in vitro evidence, their causal contribution to cortical network activity and sensory information processing in vivo remains unresolved. Here we report that selective photostimulation of astrocytes with channelrhodopsin-2 in primary visual cortex enhances both excitatory and inhibitory synaptic transmission, through the activation of type 1a metabotropic glutamate receptors. Photostimulation of astrocytes in vivo increases the spontaneous firing of parvalbumin-positive (PV(+)) inhibitory neurons, while excitatory and somatostatin-positive (SOM(+)) neurons show either an increase or decrease in their activity. Moreover, PV(+) neurons show increased baseline visual responses and reduced orientation selectivity to visual stimuli, whereas excitatory and SOM(+) neurons show either increased or decreased baseline visual responses together with complementary changes in orientation selectivity. Therefore, astrocyte activation, through the dual control of excitatory and inhibitory drive, influences neuronal integrative features critical for sensory information processing.
| S-EPMC4075037 | biostudies-literature
Project description:Optogenetics has revolutionized neurosciences by allowing fine control of neuronal activity. An important aspect for this control is assessing the activation and/or adjusting the stimulation, which requires imaging the entire volume of optogenetically-induced neuronal activity. An ideal technique for this aim is fUS imaging, which allows one to generate brain-wide activation maps with submesoscopic spatial resolution. However, optical stimulation of the brain with blue light might lead to non-specific activations at high irradiances. fUS imaging of optogenetic activations can be obtained at these wavelengths using lower light power (< 2mW) but it limits the depth of directly activatable neurons from the cortical surface. Our main goal was to report that we can detect specific optogenetic activations in V1 even in deep layers following stimulation at the cortical surface. Here, we show the possibility to detect deep optogenetic activations in anesthetized rats expressing the red-shifted opsin ChrimsonR in V1 using fUS imaging. We demonstrate the optogenetic specificity of these activations and their neuronal origin with electrophysiological recordings. Finally, we show that the optogenetic response initiated in V1 spreads to downstream (LGN) and upstream (V2) visual areas.
| S-EPMC8206208 | biostudies-literature
Project description:Our perception of how objects are laid out in visual scenes is remarkably stable, despite rapid shifts in the patterns of light that fall on the retina with each saccade. One mechanism that may help establish perceptual stability is border ownership assignment. Studies in macaque area V2 have identified border ownership neurons that signal which side of a border belongs to a foreground surface. This signal persists for hundreds of milliseconds after border ownership has been rendered ambiguous by deleting the stimulus features that distinguish foreground from background. Remarkably, this signal survives eye movements: border ownership neurons also exhibit border ownership signals de novo when an eye movement places the newly ambiguous border within their receptive field. The grouping cell hypothesis proposes the existence of hypothetical grouping cells in a downstream brain area. These cells would compute persistent proto-object representations and therefore have the properties to endow cells in upstream brain areas with selectivity for border ownership. Such grouping cells have been predicted to show a centripetal and persistent pattern of preferred side of ownership for a border placed parallel to the perimeter of their classical receptive field, and such a centripetal ownership preference pattern should also occur de novo in these same cells if an ambiguous border lands in their receptive field after a saccade. It is unknown if grouping cells exist. Here we used laminar multielectrodes in area V4 - the main source of feedback to V2 - of behaving macaques to determine whether such grouping cells exist. Consistent with the model prediction we find a substantial population of neurons with these properties, in all laminar compartments, and they exhibit a response latency that is short enough to act as the source that endows neurons in V2 with selectivity for border ownership. While grouping cell activity provides information about the location of foreground surfaces, these neurons are, counterintuitively, not as strongly tuned for luminance contrast polarity, a feature of those surfaces, as are border ownership cells. Our data suggest a division of labor in which these newly discovered grouping cells provide spatiotemporal continuity of segmented surfaces whereas border ownership cells link this location information with surface features such as luminance contrast.
| S-EPMC10827172 | biostudies-literature
Project description:Humans and other primates rely on eye movements to explore visual scenes and to track moving objects. As a result, the image that is projected onto the retina-and propagated throughout the visual cortical hierarchy-is almost constantly changing and makes little sense without taking into account the momentary direction of gaze. How is this achieved in the visual system? Here, we show that in primary visual cortex (V1), the earliest stage of cortical vision, neural representations carry an embedded "eye tracker" that signals the direction of gaze associated with each image. Using chronically implanted multi-electrode arrays, we recorded the activity of neurons in area V1 of macaque monkeys during tasks requiring fast (exploratory) and slow (pursuit) eye movements. Neurons were stimulated with flickering, full-field luminance noise at all times. As in previous studies, we observed neurons that were sensitive to gaze direction during fixation, despite comparable stimulation of their receptive fields. We trained a decoder to translate neural activity into metric estimates of gaze direction. This decoded signal tracked the eye accurately not only during fixation but also during fast and slow eye movements. After a fast eye movement, the eye-position signal arrived in V1 at approximately the same time at which the new visual information arrived from the retina. Using simulations, we show that this V1 eye-position signal could be used to take into account the sensory consequences of eye movements and map the fleeting positions of objects on the retina onto their stable position in the world.
| S-EPMC6519108 | biostudies-literature
Project description:BackgroundRecent neuroimaging studies have revealed that putatively unimodal regions of visual cortex can be activated during auditory tasks in sighted as well as in blind subjects. However, the task determinants and functional significance of auditory occipital activations (AOAs) remains unclear.Methodology/principal findingsWe examined AOAs in an intermodal selective attention task to distinguish whether they were stimulus-bound or recruited by higher-level cognitive operations associated with auditory attention. Cortical surface mapping showed that auditory occipital activations were localized to retinotopic visual cortex subserving the far peripheral visual field. AOAs depended strictly on the sustained engagement of auditory attention and were enhanced in more difficult listening conditions. In contrast, unattended sounds produced no AOAs regardless of their intensity, spatial location, or frequency.Conclusions/significanceAuditory attention, but not passive exposure to sounds, routinely activated peripheral regions of visual cortex when subjects attended to sound sources outside the visual field. Functional connections between auditory cortex and visual cortex subserving the peripheral visual field appear to underlie the generation of AOAs, which may reflect the priming of visual regions to process soon-to-appear objects associated with unseen sound sources.
| S-EPMC2644787 | biostudies-literature
Project description:Normalization has been proposed as a canonical computation that accounts for a variety of nonlinear neuronal response properties associated with sensory processing and higher cognitive functions. A key premise of normalization is that the excitability of a neuron is inversely proportional to the overall activity level of the network. We tested this by optogenetically activating excitatory neurons in alert macaque primary visual cortex and measuring changes in neuronal activity as a function of stimulation intensity, with or without variable-contrast visual stimulation. Optogenetic depolarization of excitatory neurons either facilitated or suppressed baseline activity, consistent with indirect recruitment of inhibitory networks. As predicted by the normalization model, neurons exhibited sub-additive responses to optogenetic and visual stimulation, which depended lawfully on stimulation intensity and luminance contrast. We conclude that the normalization computation persists even under the artificial conditions of optogenetic stimulation, underscoring the canonical nature of this form of neural computation.
| S-EPMC4534089 | biostudies-literature
Project description:A specific memory is thought to be encoded by a sparse population of neurons. These neurons can be tagged during learning for subsequent identification and manipulation. Moreover, their ablation or inactivation results in reduced memory expression, suggesting their necessity in mnemonic processes. However, the question of sufficiency remains: it is unclear whether it is possible to elicit the behavioural output of a specific memory by directly activating a population of neurons that was active during learning. Here we show in mice that optogenetic reactivation of hippocampal neurons activated during fear conditioning is sufficient to induce freezing behaviour. We labelled a population of hippocampal dentate gyrus neurons activated during fear learning with channelrhodopsin-2 (ChR2) and later optically reactivated these neurons in a different context. The mice showed increased freezing only upon light stimulation, indicating light-induced fear memory recall. This freezing was not detected in non-fear-conditioned mice expressing ChR2 in a similar proportion of cells, nor in fear-conditioned mice with cells labelled by enhanced yellow fluorescent protein instead of ChR2. Finally, activation of cells labelled in a context not associated with fear did not evoke freezing in mice that were previously fear conditioned in a different context, suggesting that light-induced fear memory recall is context specific. Together, our findings indicate that activating a sparse but specific ensemble of hippocampal neurons that contribute to a memory engram is sufficient for the recall of that memory. Moreover, our experimental approach offers a general method of mapping cellular populations bearing memory engrams.
| S-EPMC3331914 | biostudies-literature
Project description:Brain stimulation and imaging studies in humans have highlighted a key role for the prefrontal cortex in clinical depression; however, it remains unknown whether excitation or inhibition of prefrontal cortical neuronal activity is associated with antidepressant responses. Here, we examined cellular indicators of functional activity, including the immediate early genes (IEGs) zif268 (egr1), c-fos, and arc, in the prefrontal cortex of clinically depressed humans obtained postmortem. We also examined these genes in the ventral portion of the medial prefrontal cortex (mPFC) of mice after chronic social defeat stress, a mouse model of depression. In addition, we used viral vectors to overexpress channel rhodopsin 2 (a light-activated cation channel) in mouse mPFC to optogenetically drive "burst" patterns of cortical firing in vivo and examine the behavioral consequences. Prefrontal cortical tissue derived from clinically depressed humans displayed significant reductions in IEG expression, consistent with a deficit in neuronal activity within this brain region. Mice subjected to chronic social defeat stress exhibited similar reductions in levels of IEG expression in mPFC. Interestingly, some of these changes were not observed in defeated mice that escape the deleterious consequences of the stress, i.e., resilient animals. In those mice that expressed a strong depressive-like phenotype, i.e., susceptible animals, optogenetic stimulation of mPFC exerted potent antidepressant-like effects, without affecting general locomotor activity, anxiety-like behaviors, or social memory. These results indicate that the activity of the mPFC is a key determinant of depression-like behavior, as well as antidepressant responses.
| S-EPMC3004756 | biostudies-literature