Rostro-caudal specificity of corticospinal tract projections in mice

Abstract

Rostro-caudal specificity of corticospinal tract (CST) projections from different areas of the cortex was assessed by retrograde labeling with fluorogold and retrograde transfection following retro-AAV/Cre injection into the spinal cord of tdT-reporter mice. Injections at C5 led to retrograde labeling of neurons throughout forelimb area of the sensorimotor cortex, the rostral forebrain area (RFA), and a region in the lateral cortex near the barrel field. Injections at L2 led to retrograde labeling of neurons in the posterior sensorimotor cortex (hindlimb area) but not the RFA or lateral cortex. With BDA injections into the main sensorimotor cortex (forelimb region), labeled axons terminated selectively at cervical levels. With BDA injections into caudal sensorimotor cortex (hindlimb region), labeled axons passed through cervical levels without sending collaterals into the gray matter and then elaborated terminal arbors at thoracic-sacral levels. With BDA injections into the RFA and lateral cortex near the barrel field, labeled axons terminated at high cervical levels. Axons from medial sensorimotor cortex terminated primarily in intermediate laminae; Axons from lateral sensorimotor cortex terminated primarily in deep layers of the dorsal horn. One of the descending pathways seen in rats (the ventral CST) was not observed in most mice.SIGNIFICANCEMice are used extensively for studies of regeneration following spinal cord injury because of the ability to create genetic modifications to explore ways to enhance repair and enable axon regeneration. A particular focus has been the corticospinal tract (CST) because of its importance for voluntary motor function. Here, we document features of the rostro-caudal specificity of CST

Brain-wide analysis of the supraspinal connectome reveals anatomical correlates to functional recovery after spinal injury

“…This likely reflects the relative concentration of fluorescence in the nucleus, augmented by slower protein turnover and reduced interference from intervening axon tracts. Our direct comparison of cytoplasmic versus nuclear labeling indicates that previous studies using cytoplasmic FPs, including our own and a recent description of CST neurons in cleared brains, likely underestimated the number of retrogradely transduced neurons (Steward et al, 2021;Wang et al, 2018). Thus nuclear-localized mSc and mGL expand the tool kit for neuronal labeling in cleared tissue and allow flexibility in dual labeling experiments.…”

“…Prior work from our lab and others has combined retrograde viral labeling with 3D imaging to reveal supraspinal neurons and axons, with highly effective labeling in corticospinal tract (CST) and other neurons (Asboth et al, 2018; Frezel et al, 2020; Steward et al, 2021; Wang et al, 2018). Although informative, one limitation was dim label in some subcortical populations, compounded in the brainstem by optical interference from the nearby pyramidal and other descending tracts.…”

“…Interestingly, a rim of cervically labeled cells completely surrounded the lumbar region ( Figure 3O ). Thus lumbar-projecting CST neurons can be described most accurately not as a separate population located caudally, but rather as nested within a broader region of cervical-projecting neurons (Steward et al, 2021). Interesting, the lumbar-projecting region also displayed sparse cervical label.…”

“…Prior work from our lab and others has combined retrograde viral labeling with 3D imaging to reveal supraspinal neurons and axons, with highly effective labeling in corticospinal tract (CST) and other neurons (Asboth et al, 2018;Frezel et al, 2020;Steward et al, 2021;Wang et al, 2018).…”

Single-Cell Transcriptional Profiling of the Adult Corticospinal Tract Reveals Forelimb and Hindlimb Molecular Specialization

“…43 However, the presence of dual labeled CSNs in our study and others, suggests that these neurons are either unique to the rodent or perhaps are functionally silent in the intact spinal cord, but may be pre-wired to assume an auxiliary role in the event of trauma or degeneration. [44][45][46] Indeed, previous work from the Schwab lab has highlighted a potential functional role of these FL/HL CSNs after CNS trauma. They found an increase in functional sprouting of HL CSNs into the cervical spinal cord after stroke and SCI.…”