Visual object recognition is central to quality of life in health and disease, but it is not understood at a deep, mechanistic level. For example, while primate inferior temporal cortex (IT) is likely a key neuronal processing bottleneck, we still have only a dim understanding of its causal role at a fine spatial and temporal grain. This exploratory proposal (R21) aims to deploy, characterize, and behaviorally validate novel tools to produce spatially precise, temporally delimited silencing of neuronal activity in the IT cortex of the awak, behaving primate. Concretely, we want to choose a mm-scale location on a magnetic resonance image of a non-human primate brain, and then ask: what is the importance of normally-evoked neuronal activity at that location in supporting a given behavioral task? Rather than try to inject neuronal signals, our strategy is to develop methods to briefly (10-300 ms) block the neuronal activity that normally intervenes between visual stimulus onset and the animal's reaction time. To that end, this exploratory proposal has two synergistic aims: First, our preliminary results show that virally delivered optically-gated silencing molecules can indeed produce strong silencing of neuronal activity in IT cortex, but we have little understanding of the reliability, spatial extent and temporal limits of this silencing. Thus, we will (Aim 1) make x-ray targeted viral injections, followed by x-ray targeted optical fiber implantation, and spatially precise (~10 um) maps of neuronal silencing (or enhancement) effects in and around the optical fiber tip at multiple sites in IT cortex. The expected outcome is a spatiotemporal map of light-induced neuronal silencing around the optical fiber tip, and its dependence on light intensity, duration and latency. Second, we do not know if optical silencing of IT sub-regions leads to measurable behavioral effects on object recognition tasks. Thus, we have developed recognition tasks that are likely to be affected by IT silencing, and we have already discovered that pharmacological neuronal silencing at specific IT sub-regions (muscimol) leads to behavioral deficits in at least one recognition task (but not all such tasks). We now aim (Aim2) to test the ability of optical silencing tools to produce behavioral deficits in that same task at those same locations. The expected outcome is a demonstration that optical silencing of IT sub-regions can produce specific behavioral recognition deficits, as well as a comparison with pharmacologically induced deficits. If successful, the proposed work will enable entirely new lines of interventional work to systematically test the causal role of IT cortex in visual object recognition, and will contribute o a still nascent, but promising toolbox of optical techniques for systems-level questions in primates.

Public Health Relevance

Visual object and face recognition are fundamental to our well-being. While our brain is remarkably good at accomplishing these challenging tasks, we do not yet know how it does so. The goal of these experiments is develop new interventional tools to discover the precise locations and times of neuronal activity that the brain uses to accomplish object and face recognition -- processes that allow us to see, evaluate, and, remember the visual world.

National Institute of Health (NIH)
National Eye Institute (NEI)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (SPC)
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Steinmetz, Michael A
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Massachusetts Institute of Technology
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United States
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