Project Summary/Abstract
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.