Neuronal signals travel the cerebral cortex through local, feedforward and feedback projections. Although many studies have examined the function of local and feedforward connections, the role of feedback connections remains poorly understood. Previous work has utilized a variety of methodologies, including pharmacological inactivation, electrical microstimulation, cortical cooling and transcranial magnetic stimulation to study feedback projections. However, these techniques are limited, as they cannot specifically suppress feedback terminals without altering feedforward processing. For example, studies using pharmacological methods inject a drug into a higher cortical area in order to suppress feedback to lower cortical areas. The drug, however, inherently suppresses the feedforward signals leaving the higher cortical area. In addition to being spatially imprecise, these methods are also temporally imprecise ? these techniques work on the order of minutes to hours whereas neuronal signals are modulated on the order of milliseconds. Furthermore, previous studies focus on single unit analysis, without examining the network-level effects of feedback or laminar location of the feedback projections. In order to address these limitations, we will use an optogenetic construct (AAV8-hSyn-Jaws-GFP) to selectively suppress feedback signals, as optogenetic methods allow for temporally and spatially precise manipulations. We will combine optogenetics and electrophysiology in an unprecedented manner in the nonhuman primate to examine the functional role of feedback in the visual system. Mid-level visual cortex (V4), which has been implicated in cognitively demanding processes (like attention), sends feedback projections to the superficial layers of the primary visual cortex (V1). The injected virus will express in all parts of the V4 neurons, including their axons which project to V1. This allows us to optically stimulate the transfected V4 feedback terminals in V1, without perturbing the feedforward processing in V4. Our working hypothesis is that feedback connections exhibit functional specificity, and increase the population coding accuracy and communication among cortical neurons. We will determine how suppressing V4 feedback terminals in V1 influences single cell and network level stimulus encoding (Aim 1), behavioral performance (Aim 2), and attentional modulation (Aim 3). Specifically, we expect that suppressing V4 feedback terminals in V1 will (i) decrease gain and strength of tuning, and increase noise correlations (Aim 1), (ii) decrease performance in an orientation discrimination task (Aim 2) and, (iii) decrease gain and increase noise correlations in attended compared to unattended trials (Aim 3). We also expect that the supragranular layer, targeted by feedback projections, will show larger effects compared to the granular and infragranular layers, avoided by feedback projections. The experiments in this proposal will determine the single neuron and network-level effects of feedback in the visual system, and further, examine how feedback influences behavior and attentional modulation. The findings will have a lasting impact on our basic understanding of cortical communication, with long-term influences on clinical applications like visual prosthetics.

Public Health Relevance

We propose to causally manipulate an important type of brain connectivity, feedback projections, believed to play a major role in attention, expectation, and decision making. To accomplish this goal, we plan to selectively suppress feedback projections and record the responses of neurons while animals perform a behavioral task. These efforts can offer new insights into a network-based understanding of perceptual decisions, and help improve future visual prosthetic devices that would take into account feedback projections, which are a general type of connectivity found in the brain of all mammalian species.

National Institute of Health (NIH)
National Eye Institute (NEI)
Predoctoral Individual National Research Service Award (F31)
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Special Emphasis Panel (ZRG1)
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Agarwal, Neeraj
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University of Texas Health Science Center Houston
Schools of Medicine
United States
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