ANATOMICAL MAPPING OF THE CORTICO-RETICULOSPINAL PATHWAY IN MICE

Voluntary movement is regulated by the sensorimotor cortex, which generates motor commands and modulates sensory afferents via the corticospinal tract (CST). However, work conducted in our laboratory has shown that in the absence of the CST, the cortex can still initiate movements, suggesting the existence of parallel motor control pathways. The cortico-reticulo-spinal (CRS) pathway, in which cortical neurons project to reticulospinal neurons (RSn), may serve as one such alternative route. While CRS projections have been physiologically demonstrated in cats and primates, their precise anatomical organization in rodents remains poorly characterized. Thus, using advanced viral strategies—retrograde, anterograde, and trans-synaptic—we aim to systematically map the CRS pathway in the mouse. Preliminary results show that anterograde trans-synaptic labeling efficiently identifies cortical projections to RSn. We confirmed the existence of direct cortical input to RSn (RSn/CI), supporting the presence of a CRS pathway in mice. Preliminary results indicate that the CRS pathway exhibits a stereotyped anatomical organization regardless of cortical origin, with RSn/CI concentrated primarily in pontine reticular nuclei (PRN) and gigantocellular reticular nucleus (GRN). Notably, lateral sensory cortex, despite lacking direct lumbar CS projections, communicates indirectly with lumbar spinal circuits via the reticular formation, suggesting parallel sensory-to-motor transformation pathways, while medial cortex controls the same lumbar spinal region through both direct (CS) and indirect (CRS) routes, potentially enabling flexible and robust motor control through pathway redundancy. Ongoing experiments aim to determine and characterize the molecular profile of these RSn/Cl neurons using immunohistochemistry and RNAscope to precisely define their cellular identity.