Multisynaptic projections from the ventrolateral prefrontal cortex to hand and mouth representations of the monkey primary motor cortex

• Multisynaptic inputs from prefrontal cortex to motor cortex (MI) were examined.
• Ventral area 46 projects preferentially to the MI hand and mouth regions.
• Orbitofrontal cortex projects predominantly to the MI mouth region.

Different sectors of the prefrontal cortex have distinct neuronal connections with higher-order sensory areas and/or limbic structures and are related to diverse aspects of cognitive functions, such as visual working memory and reward-based decision-making. Recent studies have revealed that the prefrontal cortex (PF), especially the lateral PF, is also involved in motor control. Hence, different sectors of the PF may contribute to motor behaviors with distinct body parts. To test this hypothesis anatomically, we examined the patterns of multisynaptic projections from the PF to regions of the primary motor cortex (MI) that represent the arm, hand, and mouth, using retrograde transsynaptic transport of rabies virus. Four days after rabies injections into the hand or mouth region, particularly dense neuron labeling was observed in the ventrolateral PF, including the convexity part of ventral area 46. After the rabies injections into the mouth region, another dense cluster of labeled neurons was seen in the orbitofrontal cortex (area 13). By contrast, rabies labeling of PF neurons was rather sparse in the arm-injection cases. The present results suggest that the PF-MI multisynaptic projections may be organized such that the MI hand and mouth regions preferentially receive cognitive information for execution of elaborate motor actions.