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Optogenetic examination of the role of feedback on visual processing and perception (NeuroOptoGen)
Start date: Jul 1, 2012, End date: Jun 30, 2017 PROJECT  FINISHED 

We need to understand the brain mechanisms of perception and cognition in order to develop treatments for disorders in which these abilities fail, such as schizophrenia, attention-deficit-hyperactivity disorder or autism. Over the past half-century neurophysiologists have enormously advanced our knowledge of how the feed-forward connections give rise to the response properties in the visual cortex. However, although we know from anatomy that most afferents in cortex constitute feedback projections, their function is still largely unknown.Visual perception in humans and monkeys depends on context. These perceptual phenomena are thought to be mediated by feedback, and many are altered in schizophrenic patients. Understanding the role of feedback is therefore important not only for unraveling fundamental mechanisms of cognition, but also for addressing their dysfunction in cognitive disorders. Until now technical limitations have made it nearly impossible to test the role of feedback.Novel approaches allow us to examine the role of cortico-cortical feedback in visual perception in the behaving monkey. We will use optogenetic techniques and retrograde viral vectors (lentivirus pseudotyped with rabies glycoprotein) to target specific monosynaptic cortico-cortical projections in vivo. By expressing the light-sensitive proteins channelrhodopsin2 (ChrR2) or archaerhodopsin (Arch) in these projection neurons, we can activate (ChR2) or inactivate (Arch) them with light. We will combine this approach with multi-channel electrophysiology, behavior and computational analyses. We will first quantify the effect of (in)activating cortico-cortical feedback from visual cortex V2 on the neuronal responses in the primary visual, and then on the monkey’s visual perception during tasks manipulating attention. If successful, this work will help advance our functional understanding of feedback, and may open the possibility to examine the function of any connection in the primate brain.

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