Task Demand-dependent Contribution of Frontal-Sensory Cortical Projections to Attentional Behavior in Mice

Top-down attention is a dynamic cognitive process that facilitates the detection of the task-relevant stimuli from our complex sensory environment. A neural mechanism capable of deployment under specific task-demand conditions would be crucial to efficiently control attentional processes and promote goal-directed attention performance in task-demand dependent manner. Previous studies have shown that frontal top-down neurons projecting from the anterior cingulate area (ACA) to the visual cortex (VIS; ACAVIS) are required for attentional behavior during the 5-choice serial reaction time task (5CSRTT) in mice. However, it is unknown whether the contribution of this projecting neurons is dependent on the extent of task demand. Here, we examine the differential contribution of ACAVIS projection neurons to the attentional behavior in adult male mice performing two visual attention tasks of varying task demand: the 5CSRTT and 2-choice serial reaction time task (2CSRTT). We found that optogenetic suppression ACAVIS projections immediately before stimulus presentation has no effect during the 2CSRTT in contrast to the impaired performance during the 5CSRTT. Fiber photometry calcium imaging of ACAVIS neuron activity revealed that these neurons, which are recruited after errors during 5CSRTT, are not recruited during 2CSRTT. These results suggest that ACAVIS projections are necessary only when task demand is high and that ACAVIS neuron activity may not provide an error monitoring signal when task demand is low. Collectively, this frontal-sensory ACAVIS projection regulates visual attention behavior during specific high task demand conditions, pointing to a flexible circuit-based mechanism for promoting attentional behavior. Significance Statement Task demand-dependent recruitment of neural circuits would be essential for efficient attentional control. Anterior cingulate area projections to the visual cortex (ACAVIS) are required for attentional behavior in mice, but it is uncertain whether this is task-demand dependent. We first established that visual attentional performance is dependent on task demand, before using an inhibitory optogenetic approach to demonstrate that ACAVIS projections play a causal role in the anticipatory attention only during high task demand conditions. Also, circuit-selective fiber photometry recordings showed that ACAVIS projections are recruited following errors during high, but not low, task demand conditions. This finding advances our understanding of flexible circuit-based mechanisms for promoting attentional behavior that may underlie task-demand dependent behavior deficits in psychiatric disorders. ### Competing Interest Statement The authors have declared no competing interest.