This project aims to elucidate the dynamics, population correlation changes, and cell types involved in divisive normalization in mouse V1. Divisive normalization is a canonical nonlinear computation that allows for multisensory integration, and that is carried out by populations of neurons. In the computation, the response of one neuron to a given stimulus is a weighted average of its response to all stimuli shown ? not just its preferred stimulus. Divisive normalization underlies sensory modalities as diverse as olfactory integration in fruit flies and photoreceptor adaptation from light to dark environments, as well as higher-order cognitive functions like decision-making in monkey parietal cortex and changes in neural correlates of attention in monkey. When central brain computations go awry, the consequences can be severe ? and divisive normalization has been implicated in brain disorders like autism. While divisive normalization is a ubiquitous and potentially clinically relevant brain computation, its functional circuitry, and even the cell types involved in the computation, remain unknown. This project aims to address that gap in understanding. To complete this project, I will investigate divisive normalization in mouse visual cortex. A mouse model will enable the use of powerful in vivo genetic, electrophysiology, imaging, optogenetic, and psychophysics techniques. Here, I will use transgenic and viral transfections to functionally label excitatory and inhibitory neurons in mouse V1. Through a surgically implanted chronic window, I will use state-of-the-art two-photon imaging to capture the activity of V1 excitatory and inhibitory neuron populations in awake, ambulating mice presented with stimuli that evoke divisive normalization. Additionally, I will optogenetically manipulate inhibitory populations during divisive normalization. To analyze my data, I will use advanced computational approaches to model circuit activity. These experiments will further elucidate the functional population dynamics and cell type contributions involved in divisive normalization. We anticipate this project will provide groundwork for continuing to study divisive normalization in the mouse and may ultimately lead to circuit dissection and behavioral assays, contributing to an understanding of the role of divisive normalization in normal physiology and behavior, aberrant circuitry, and disease.

Public Health Relevance

The goal of this proposal is to elucidate the dynamics, correlation changes, and cell types involved in divisive normalization, a canonical computation, in mouse V1. The proposed research will answer questions about the spatial, temporal, layer-specific, cell-type, and population dynamics during divisive normalization, a nonlinearity relevant for multisensory information processing. This will facilitate and understanding of normal brain computations which may be relevant for understanding and treating neurological and psychiatric disorders.

National Institute of Health (NIH)
National Eye Institute (NEI)
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
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Special Emphasis Panel (ZRG1)
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Agarwal, Neeraj
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University of Chicago
Schools of Medicine
United States
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