Chemogenetic suppression of anterior cingulate cortical neurons projecting to the visual cortex disrupts attentional behavior in mice

Aim: Attention is a goal-directed cognitive process that facilitates the detection of task-relevant sensory stimuli from dynamic environments. Anterior cingulate cortical area (ACA) is known to play a key role in attentional behavior, but the specific circuits mediating attention remain largely unknown. As ACA modulates sensory processing in the visual cortex (VIS), we aim to test a hypothesis that frontal top-down neurons projecting from ACA to VIS (ACA_VIS ) contributes to visual attention behavior through chemogenetic approach.

Methods: Adult, male mice were trained to perform the 5-choice serial reaction time task (5CSRTT) using a touchscreen system. An intersectional viral approach was used to selectively express inhibitory designer receptors exclusively activated by designer drugs (iDREADD) or a static fluorophore (mCherry) in ACA_VIS neurons. Mice received counterbalanced injections (i.p.) of the iDREADD ligand (clozapine-N-oxide; CNO) or vehicle (saline) prior to 5CSRTT testing. Finally, mice underwent progressive ratio testing and open field testing following CNO or saline administration.

Results: Chemogenetic suppression of ACA_VIS neuron activity decreased correct task performance during the 5CSRTT mainly driven by an increase in omission and a trending decrease in accuracy with no change in behavioral outcomes associated with motivation, impulsivity, or compulsivity. Breakpoint during the progressive ratio task and distance moved in the open field test were unaffected by ACA_VIS neuron suppression. CNO administration itself had no effect on task performance in mCherry-expressing mice.

Conclusion: These results identify long-range frontal-sensory ACA_VIS projection neurons as a key enactor of top-down attentional behavior and may serve as a beneficial therapeutic target.