Projection-specific and reversible functional blockage in the association cortex of macaque monkeys

The functional manipulation techniques based on optogenetics have been widely and effectively utilized in the rodent brain. However, the applications of these techniques to the macaque cerebral cortex, particularly those to the prefrontal cortex, have been limited due to the extensive size and complex functional organization of each prefrontal area. In this study, we developed projection-specific and reversible functional blockade methods applicable to areas of the macaque prefrontal cortex, based on chemogenetic techniques. In chemogenetics, once a pair of viral vectors has been injected into the regions of projection source and target, the projection-specific functional blockage can be initiated through the oral, intravenous, or intramuscular administration of an appropriate pharmaceutical agent. Two methods were developed using two different effector proteins, an inhibitory DREADD, hM4Di, and tetanus toxin, given the substantial discrepancy in the on-off time course of functional blockade between the two. The Cre-DIO system was combined with hM4Di, and the Tet-On system with tetanus toxin. The effectiveness of these methods was evaluated by developing an electrophysiological assay using photic stimulation and field potential recordings.