The orbitofrontal cortex (OFC) plays an important role in flexible, outcome-guided behavior. Studies in rodents and monkeys have demonstrated that the identity and expected values of specific outcomes are represented by activities in the OFC.

Lesions or inactivation of the OFC impair behavior guided by outcome expectancy and learning driven by the discrepancy between expected and actual outcomes. Direct output from the OFC to other brain regions, including the basolateral amygdala, ventral tegmental area and striatum, is important for learning and reward-related behavior. The OFC also projects to sensory cortices, including primary visual cortex (V1), yet the function of this top-down projection is unclear.

In a study published online in Nature Communications on June 3, the researchers from Dr. YAO Haishan’s Lab at the Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology of the Chinese Academy of Sciences revealed that the top-down projection from OFC to primary visual cortex contributes to visual associative learning.

The researchers first examined how OFC top-down projection influences V1 neuronal responses.

They found that activating OFC axons in V1 significantly reduced the firing rates of V1 neurons in both anesthetized and awake mice. Using slice recording and in vivo fiber photometry recording, they found that activating OFC top-down projection preferentially activated somatostatin (SST) interneurons in V1.

The researchers hypothesized that OFC projection to V1 may function during task engagement to suppress V1 responses to non-relevant visual stimulus. They trained mice to perform a Go/No-Go visual task, in which the Go stimulus and the No-Go stimulus were associated with water reward and no reward, respectively.

The results showed that learning of the task depended on the improvement of correct rejection for the reward-irrelevant No-Go stimulus. In mice performing a Go/No-Go visual task, V1 responses to the reward-irrelevant No-Go stimulus were lower when the mice' outcome expectation was correct than when it was incorrect, and such response modulation was reduced by optogenetic inactivation of OFC projection to V1. Using optogenetic tagging technique, the researchers found that the V1-projecting OFC neurons reduced firing during expectation of reward.

Besides, the researchers found that chronic optogenetic inactivation of OFC projection to V1 slowed the learning of Go/No-Go visual task, and chronic activation of SST interneurons in V1 improved the learning.

This study demonstrates that the OFC projection to V1 plays a key role in filtering out non-relevant visual information to facilitate associative learning.