Functional properties and computational function of top-down feedback in early visual cortex: an optogenetic investigation

University Of Utah, Salt Lake City UT

Investigators

Abstract

Cognitive functions such as thinking, perceiving and remembering, rely on the coordinated activity of neurons in the cerebral cortex, the site of conscious experience. In the cerebral cortex of higher mammals, sensory information travels along feedforward connections through a hierarchy of cortical areas, each processing increasingly complex stimulus features. In turn, higher processing areas send much denser feedback connections to lower processing areas. The role of feedback connections in sensory processing has remained hypothetical due to unavailability of methods for rapid and selective perturbation of feedback circuit activity. The goal of the studies proposed in this application is to understand the role of feedback in the processing of sensory stimuli, using optogenetics. This is a novel methodology, which allows to selectively and rapidly perturb, using light, the activity of feedback neurons expressing light-sensitive excitatory or inhibitory opsins derived from bacteria. In turn, opsin expression in feedback neurons is induced via injections into the cortex of viruses carrying the exogenous opsin gene. The interdisciplinary nature of the proposal will offer a unique opportunity to train young graduate and undergraduate students in both neuroscience and mathematics. Women and minority undergraduate students will be specifically recruited working with existing outreach local programs. Moreover, use of optogenetics to understand the function of feedback circuits in higher mammals is a major technical innovation, which will have a major impact on studies of neural circuit function in higher mammalian species. Optogenetic activation will be used to identify feedback neurons in different cortical areas and characterize their specific functional properties (Aim 1). This will reveal the unique properties of feedback neurons and how they differ from those of feedforward or other cortical neurons. Instead, optogenetic inactivation will be used to determine how silencing feedback from higher cortical areas affects the processing of sensory stimuli in lower cortical areas (Aim 2). Finally, computational modeling will be used to understand how feedback neuron activity affects the cortical network and its dynamics (Aim 3). In particular, the modeling work will reveal how the complex interactions between feedback neurons and other cortical circuits generates the results observed in the experimental studies. Together, the proposed studies will increase understanding of how the cerebral cortex works by revealing the role of feedback connections in sensory information processing. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.