Parvalbumin-containing neurons mediate the feedforward inhibition of rat rubrospinal neurons

The calcium-binding protein, parvalbumin and glutamic acid decarboxylase immunohistochemistry were used to locate candidate neurons mediating the inhibition of rat rubral neurons. A group of cells with small to medium-sized cell bodies that reacted positively to both were found in the red nucleus and its immediate vicinity. At the caudal nuclear level, these neurons gathered in the reticular formation, the pararubral area dorsolateral to the nucleus. As the nucleus expanded in size rostrally these neurons started to incorporate into the nucleus at about the anterior half of the middle nucleus and were all located within the rostral nucleus. Since these neurons were spatially segregated from the caudal nucleus we tested their connection by applying anterograde tracer to the pararubral area at the caudal red nuclear level. Labeled fibers with bouton-like swellings were found to enter the caudal nucleus and closely apposed rubrospinal neuronal cell bodies. These findings are consistent with our earlier observation that stimulating the pararubral area elicited a monosynaptic gamma-aminobutyric-acid(A) receptor-mediated inhibition on rubrospinal neurons in brainstem slices. In addition, the present study also shows that these inhibitory neurons remained unaltered in rats subjected to unilateral upper cervical rubrospinal tractotomy, suggesting that the reduction of pararubral stimulus-induced inhibition on rubrospinal neurons following spinal axonal injury resulted from causes other than the loss of these inhibitory neurons. In the rats, sensorimotor cortical fibers are known to reach the rostral red nucleus and the pararubral area but not the caudal nucleus. This prompted us to propose that neocortical inputs inhibit rubrospinal neurons through the activation of these PV-containing neurons. The proposed feedforward inhibitory circuit enables the cerebral cortex to disynaptically modulate the rubrospinal control over flexor motor execution.