Debes, Dragoi publish work on optogenetic control of brain circuits in Science

By Roman Petrowski, Office of Communications

Drs. Samantha Debes and Valentin Dragoi - Science Paper

Recent research from Samantha Debes, Phd, and Valentin Dragoi, PhD, revealing for the first time that cortical feedback projections carry attentional signals to individual neurons and cell populations in visual cortex, has been published in Science.

Recent research from the lab of Valentin Dragoi, PhD, Rochelle and Max Levitt Distinguished Professor in the Neurosciences, revealing for the first time that cortical feedback projections carry attentional signals to individual neurons and cell populations in visual cortex, has been published in Science as a research article.

The first author of the paper, titled “Suppressing feedback signals to visual cortex abolishes attentional modulation,” is Samantha Debes, PhD, a recent graduate from the Dragoi Lab. Work done for the paper relies on years of research in the Dragoi Lab on applying optogenetic tools to manipulate cortical circuits and behavior and is funded by the NIH BRAIN Initiative and National Eye Institute, including an F31 fellowship to Debes from the NEI.

The paper presents the first causal evidence that the attentional modulation of individual neurons and cell populations in visual cortex is carried out by cortical feedback projections from higher areas.

“Attention is a well-known phenomenon that has been extensively studied worldwide for more than 100 years,” Dragoi said. “Despite the prominence of this phenomenon, the neural underpinnings of attention are incompletely understood.”

To collect research, animals in the lab performed hundreds of spatial attention trials whereby stimuli were presented on one side of the screen, i.e., the “attended” side, while animals ignored stimuli in the contralateral hemifield. Across sessions, the unattended and attended sides of the screen were swapped repeatedly.

Debes and Dragoi injected a suppressive viral construct into mid-level visual cortical area (V4), and then researchers shined light using a fiber optic onto the postsynaptic axonal terminals in primary visual cortex (V1) while simultaneously recording the responses of populations of neurons in both visual cortical areas, which are connected via indirect feedforward connections and direct feedback connections.

“This was an elegant method to suppress the feedback inputs that V1 cells receive without affecting the other sources of inputs received by V1 cells, such as local and feedforward signals,” Dragoi said. “Throughout this manipulation, animals performed the demanding attentional task allowing behavioral responses to be accurately measured.”

Results from the lab’s research showed that inactivating feedback axonal terminals in V1 for a fraction of a second, without altering local intracortical and feedforward inputs, reduced the response gain of single cells and impaired the accuracy of neural populations for encoding external stimuli. The effects of the inactivation were modest in individual cells, however, when looking at large neural populations, the changes were highly significant, indicating that attention primarily influences neural computations at the network level.

“These results are important because they provide the first evidence that attention casually enhances sensory coding across the visual cortex by specifically altering the strength of corticocortical feedback in a layer-dependent manner,” Dragoi said. “This is a radical departure from previous studies relying on correlational, not causal, relationships between sensory coding, cortical feedback, and attention.”

The research also brings the possibility of using viral tools to dissect attentional circuits throughout the brain, and not just in the visual cortex.

“New tools need to be developed to alleviate some of the unwanted effects of light simulation,” Dragoi said. “This could potentially help uncover the large-scale subcortical and cortical circuits allowing attention to influence neural computations in many brain areas. In the near future, effective therapeutic solutions could be based on light simulation to ameliorate mental health due to severe attention deficits.”