Two of the most fundamental questions of sensory neuroscience are: 1) how is stimulus information represented by the activity of neurons at different levels of information processing? And 2) what features of this activity are read by the higher brain areas to guide behavior? The first question has been the subject of a large body of work across different sensory modalities. To answer the second question, one needs to establish a causal link between neuronal activity and behavior. In many systems, fine spatiotemporal patterns of activity underlie the neural representation of information. In these systems, deciphering the salient neural code will require manipulating sets of neurons with fine spatiotemporal resolution while monitoring behavior. Ultimately, we would like to be able to manipulate arbitrary subsets of the neurons comprising neural circuits, and to do so with precise spatiotemporal control. Further, we would like to do so during natural behavior, to provide the ability to discern the salient spatiotemporal patterns that are behaviorally relevant from the broader cacophony of activity. Olfaction is emerging as an ideal system for investigating spatiotemporal coding. Recent studies have revealed that fine temporal scales are essential to olfactory information processing, both in terms of representation and the behavioral readout. Moreover, joint spatiotemporal activity perturbations affect this readout. Here, we propose to develop and apply within the context of early olfaction an advanced holographic optogenetic technology, which will enable flexible manipulation of the spatiotemporal firing patterns of dozens of neurons within a network, down to single-neuron resolution and several milliseconds of temporal resolution. The essential code underlying the evolutionarily crucial ability to detect and to discriminate odor stimuli is carried at a very fine spatiotemporal resolution and our goal with this new approach is to dissect which features of this code are behaviorally accessible. By combining state-of-the-art tools for patterned cellular-resolution optogenetic stimulation with olfactory- guided behavioral paradigms in head-fixed mice, the proposed research is expected to contribute a powerful new approach for dissecting which features of neural codes are behaviorally accessible.

Public Health Relevance

A fundamental question in neuroscience is how the nervous system processes information under normal and pathological conditions. The experiments described in this proposal examine how cortex reads sensory codes and what are the principles of information transmission between brain areas, using the olfactory system as a model and a new optical technology. We hope that the insights from this work will lead to a better understanding of the language that neurons at multiple levels of the brain use to communicate with each other.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZNS1-SRB-S (61))
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Gnadt, James W
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New York University
Schools of Medicine
New York
United States
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