Organization of Multisynaptic Inputs from Prefrontal Cortex to Primary Motor Cortex as Revealed by Retrograde Transneuronal Transport of Rabies Virus

Abstract

The organization of multisynaptic projections from the prefrontal cortex to the primary motor cortex (MI) was examined in macaque monkeys by retrograde transneuronal transport of rabies virus. In the first series of experiments, the virus was injected into the MI forelimb region, and the time-dependent distribution patterns of transsynaptic labeling were analyzed in the frontal lobe with various survivals (2-4 d). Two days after the viral injection, neuronal labeling emerged in the caudal aspects of the nonprimary motor-related areas that are known to project to the MI directly. At the same time, the motor thalamus contained labeled neurons. On the third day, cortical labeling extended into the rostral motor-related areas and, also, prearcuate area 8. Moreover, a number of labeled neurons were located in the internal pallidum and the cerebellar nuclei. At the 4 d postinjection period, neuronal labeling occurred widely in prefrontal areas as well as in the putamen and the cerebellar cortex. In the second series of experiments, the viral injection was made into the MI hindlimb region, and the distribution pattern of prefrontal labeling on the fourth day was compared with that in the forelimb-injection case. The labeled neurons in each prefrontal area were much fewer in the hindlimb-injection case than in the forelimb-injection case. Whereas ventral area 46 was most densely labeled from the forelimb region, only sparse labeling from the hindlimb region was observed in this prefrontal area. The present results suggest the importance of ventral area 46 in the cognitive control of forelimb movements.

Segregated Pathways Carrying Frontally Derived Top-Down Signals to Visual Areas MT and V4 in Macaques

“…As neither area 46v nor SEF directly projects to MT or V4, neuronal labeling in these areas at the 3 d postinjection period verifies the trans-synaptic transport of rabies virus. Furthermore, the internal control tested in our laboratory (Miyachi et al, 2005) and the consistency of labeling patterns in V1 with previous data Ninomiya et al, 2011) indicate that neuronal labeling in area 46v and SEF is ascribable to the second-order labeling occurring at the 3 d postinjection period. However, there may exist the possibility that some weak disynaptic connections remain unlabeled with the 3 d survival time.…”

“…This strain was the same as that introduced by Ugolini (1995) and Kelly and Strick (2000) to demonstrate specific retrograde trans-synaptic transport of the virus. The rate of retrograde transport for the viral batch used in this study was calibrated in our previous study (Miyachi et al, 2005). By evaluating transneuronal labeling in the cortico-basal and cerebro-cerebellar loop circuits, we concluded that it takes ϳ2 d for first-order neuron labeling and one additional day per one synapse for subsequent transneuronal labeling.…”

“…Coronal or parasagittal sections were cut serially at 60 m thickness on a freezing microtome. In the case of rabies injections, a series of every sixth section was immunohistochemically stained for rabies virus with the standard avidin-biotin peroxidase complex (ABC) method as described previously (Miyachi et al, 2005;Ninomiya et al, 2011). Briefly, the sections were immersed in 1% skim milk for 1 h and incubated overnight at 4°C with rabbit anti-rabies antibody (diluted at 1:10,000; Inoue et al, 2003) in 0.1 M PBS containing 0.1% Triton X-100 and 1% normal goat serum.…”

Selection of Prime Actor in Humans during Bimanual Object Manipulation

“…Recent evidence suggests that the anterior cingulate cortex can produce signals specific of the first distinct reward, which marks the end of exploration (Quilodran et al, 2008). By directly and indirectly providing directions for the operational states of dlPFC as well as for the dorsal premotor areas (Miyachi et al, 2005;Tanji and Hoshi, 2008), it is likely that such signals supported the implementation of the desired action representation in the bimanual trials. Indeed, evidence in macaques during reaching indicates that arm selection involves neural processes in the dorsal premotor and supplementary motor areas Tanji, 2000, 2004).…”

Subsecond Changes in Top–Down Control Exerted by Human Medial Frontal Cortex during Conflict and Action Selection: A Combined Transcranial Magnetic Stimulation–Electroencephalography Study

“…Although spread of induced current to adjacent brain areas is possible, studies using a similar coil have reported an effective resolution of approximately a centimeter Walsh and Cowey, 2000) and the effect of dMFC TMS can be distinguished from that of adjacent dorsal premotor cortex (Rushworth et al, 2002;Kennerley et al, 2004b). Although pre-SMA is not directly interconnected with M1 or spinal cord (Luppino et al, 1993;He et al, 1995), it contains neurons that respond when hand movements are made (Fuji et al, 2001) and it is interconnected with M1 through a multisynaptic pathway (Miyachi et al, 2005). It is realistic to assume that dMFC TMS could impact on M1 activity via a multisynaptic pathway.…”