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 and a region in the dorsolateral cortex near the barrel field (S2). Injections at L2 led to retrograde labeling of neurons in the posterior sensorimotor cortex (hindlimb area) but not the dorsolateral cortex. With injections of biotinylated dextran amine (BDA) 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 dorsolateral cortex near the barrel field, labeled axons terminated at high cervical levels. Axons from medial sensorimotor cortex terminated primarily in intermediate laminae and axons from lateral sensorimotor cortex terminated primarily in laminae III–V of the dorsal horn. One of the descending pathways seen in rats (the ventral CST) was not observed in most mice.

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Rostro-caudal specificity of corticospinal tract projections in mice

10.1101/2020.07.21.214908 ◽

2020 ◽

Author(s):

Oswald Steward ◽

Kelly M. Yee ◽

Mariajose Metcalfe ◽

Rafer Willenberg ◽

Juan Luo ◽

...

Keyword(s):

Spinal Cord ◽

Sensorimotor Cortex ◽

Corticospinal Tract ◽

Descending Pathways ◽

Lateral Cortex ◽

Retrograde Labeling ◽

Barrel Field ◽

Cord Injury ◽

Deep Layers ◽

High Cervical

ABSTRACTRostro-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

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Comparison of the distribution and somatodendritic morphology of tectotectal neurons in the cat and monkey

Visual Neuroscience ◽

10.1017/s095252389815513x ◽

1998 ◽

Vol 15 (5) ◽

pp. 903-922 ◽

Cited By ~ 34

Author(s):

ETIENNE OLIVIER ◽

JOHN D. PORTER ◽

PAUL J. MAY

Keyword(s):

Superior Colliculus ◽

Cell Types ◽

Macaque Monkey ◽

Cell Type ◽

Biotinylated Dextran Amine ◽

Superior Colliculi ◽

Retrograde Labeling ◽

Biotinylated Dextran ◽

Cat Superior Colliculus

The presence of a commissure connecting the two superior colliculi suggests they do not act independently, but the function of the tectotectal connection has never been firmly identified. To develop a better understanding of this commissural system, the present study determined the distribution and morphology of tectotectal neurons in the cat and macaque monkey, two animals with well-studied, but different orienting strategies. First, we compared the distribution of tectotectal cells retrogradely labeled following WGA-HRP injections into the contralateral superior colliculus. In monkeys, labeled tectotectal cells were found in all layers, but were concentrated in the intermediate gray layer (75%), particularly dorsally, and the adjacent optic layer (12%). Tectotectal cells were distributed throughout nearly the entire rostrocaudal extent of the colliculus. In cats, tectotectal cells were found in all the layers beneath the superficial gray, but the intermediate gray layer contained the greatest concentration (56%). Labeled cells were almost exclusively located in the rostral half of the cat superior colliculus, in contrast to the monkey distribution. In the context of the representation of visuomotor space in the colliculus, the distribution of monkey and cat tectotectal cells suggests a correspondence with oculomotor range. So these neurons may be involved in directing orienting movements performed within the oculomotor range. The somatodendritic morphology of tectotectal cells in these two species was revealed by homogeneous retrograde labeling from injections of biocytin or biotinylated dextran amine into the contralateral colliculus. The cell classes contributing to this pathway are fairly consistent across the two species. A variety of neuronal morphologies were observed, so there is no single tectotectal cell type. Instead, cell types similar to those found in each layer, excepting the largest neurons, were present among tectotectal cells. This suggests that a sample of each layer's output is sent to the contralateral colliculus.

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Formation of Descending Pathways Mediating Cortical Command to Forelimb Motoneurons in Neonatally Hemidecorticated Rats

Journal of Neurophysiology ◽

10.1152/jn.00968.2009 ◽

2010 ◽

Vol 104 (3) ◽

pp. 1707-1716 ◽

Cited By ~ 23

Author(s):

Tatsuya Umeda ◽

Masahito Takahashi ◽

Kaoru Isa ◽

Tadashi Isa

Keyword(s):

Spinal Cord ◽

Sensorimotor Cortex ◽

Corticospinal Tract ◽

Descending Pathways ◽

Dorsal Funiculus ◽

Intact Side ◽

Spinal Interneurons ◽

Upper Cervical ◽

Anterograde Tracer ◽

Medullary Pyramid

Neonatally hemidecorticated rats show fairly normal reaching and grasping behaviors of the forelimb contralateral to the lesion at the adult stage. Previous experiments using an anterograde tracer showed that the corticospinal fibers originating from the sensorimotor cortex of the intact side projected aberrant collaterals to the spinal gray matter on the ipsilateral side. The present study used electrophysiological methods to investigate whether the aberrant projections of the corticospinal tract mediated the pyramidal excitation to the ipsilateral forelimb motoneurons and, if so, which pathways mediate the effect in the hemidecorticated rats. Electrical stimulation to the intact medullary pyramid elicited bilateral negative field potentials in the dorsal horn of the spinal cord. In intracellular recordings of forelimb motoneurons, oligosynaptic pyramidal excitation was detected on both sides of the spinal cord in the hemidecorticated rats, whereas pyramidal excitation of motoneurons on the side ipsilateral to the stimulation was much smaller in normal rats. By lesioning the dorsal funiculus at the upper cervical level, we clarified that the excitation was transmitted to the ipsilateral motoneurons by at least two pathways: one via the corticospinal tract and spinal interneurons and the other via the cortico-reticulo-spinal pathways. These results suggested that in the neonatally hemidecorticated rats, the forelimb movements on the side contralateral to the lesion were modulated by motor commands through the indirect ipsilateral descending pathways from the sensorimotor cortex of the intact side either via the spinal interneurons or reticulospinal neurons.

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Effects of treating traumatic brain injury with collagen scaffolds and human bone marrow stromal cells on sprouting of corticospinal tract axons into the denervated side of the spinal cord

Journal of Neurosurgery ◽

10.3171/2012.11.jns12753 ◽

2013 ◽

Vol 118 (2) ◽

pp. 381-389 ◽

Cited By ~ 26

Author(s):

Asim Mahmood ◽

Hongtao Wu ◽

Changsheng Qu ◽

Ye Xiong ◽

Michael Chopp

Keyword(s):

Spinal Cord ◽

Stromal Cells ◽

Bone Marrow Stromal Cells ◽

Corticospinal Tract ◽

Marrow Stromal Cells ◽

Control Group ◽

Axonal Sprouting ◽

Collagen Scaffolds ◽

Biotinylated Dextran Amine ◽

Biotinylated Dextran

Object This study was designed to investigate how transplantation into injured brain of human bone marrow stromal cells (hMSCs) impregnated in collagen scaffolds affects axonal sprouting in the spinal cord after traumatic brain injury (TBI) in rats. Also investigated was the relationship of axonal sprouting to sensorimotor functional recovery after treatment. Methods Adult male Wistar rats (n = 24) underwent a controlled cortical impact injury and were divided into three equal groups (8 rats/group). The two treatment groups received either hMSCs (3 × 106) alone or hMSC (3 × 106)–impregnated collagen scaffolds transplanted into the lesion cavity. In the control group, saline was injected into the lesion cavity. All treatments were performed 7 days after TBI. On Day 21 after TBI, a 10% solution of biotinylated dextran amine (10,000 MW) was stereotactically injected into the contralateral motor cortex to label the corticospinal tract (CST) originating from this area. Sensorimotor function was tested using the modified neurological severity score (mNSS) and foot-fault tests performed on Days 1, 7, 14, 21, 28, and 35 after TBI. Spatial learning was tested with Morris water maze test on Days 31–35 after TBI. All rats were sacrificed on Day 35 after TBI, and brain and spinal cord (cervical and lumbar) sections were stained immunohistochemically for histological analysis. Results Few biotinylated dextran amine–labeled CST fibers crossing over the midline were found in the contralateral spinal cord transverse sections at both cervical and lumbar levels in saline-treated (control) rats. However, hMSC-alone treatment significantly increased axonal sprouting from the intact CST into the denervated side of the gray matter of both cervical and lumbar levels of the spinal cord (p < 0.05). Also, this axonal sprouting was significantly more in the scaffold+hMSC group compared with the hMSC-alone group (p < 0.05). Sensorimotor functional analysis showed significant improvement of mNSS (p < 0.05) and foot-fault tests (p < 0.05) in hMSC-alone and scaffold+hMSC-treated rats compared with controls (p < 0.05). Functional improvement, however, was significantly greater in the scaffold+hMSC group compared with the hMSC-alone group (p < 0.05). Morris water maze testing also showed significant improvement in spatial learning in scaffold+hMSC and hMSC-alone groups compared with the control group (p < 0.05), with rats in the scaffold+hMSC group performing significantly better than those in the hMSC-alone group (p < 0.05). Pearson correlation data showed significant correlation between the number of crossing CST fibers detected and sensorimotor recovery (p < 0.05). Conclusions Axonal plasticity plays an important role in neurorestoration after TBI. Transplanting hMSCs with scaffolds enhances the effect of hMSCs on axonal sprouting of CST fibers from the contralateral intact cortex into the denervated side of spinal cord after TBI. This enhanced axonal regeneration may at least partially contribute to the therapeutic benefits of treating TBI with hMSCs.

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Plasticity to neonatal sensorimotor cortex injury

Translational Neuroscience ◽

10.2478/v10134-010-0011-1 ◽

2010 ◽

Vol 1 (1) ◽

Cited By ~ 2

Author(s):

Sarah Galley ◽

Gavin Clowry

Keyword(s):

Spinal Cord ◽

Dorsal Horn ◽

Sensorimotor Cortex ◽

Corticospinal Tract ◽

Fluorescent Protein ◽

Yellow Fluorescent Protein ◽

Red Nucleus ◽

Neuronal Cell ◽

Ventral Horn ◽

Dorsal Funiculus

AbstractA CST-YFP transgenic mouse has been developed for the study of the corticospinal tract in which yellow fluorescent protein is expressed under the control of thy1 and emx1 promoters in order to restrict expression to forebrain neurones. We explored plasticity of the developing corticospinal tract of these mice following a unilateral lesion to the sensorimotor cortex at postnatal day 7. The extent of innervation of the cervical spinal cord at time points post-lesion was assessed by measuring density of immunoperoxidase reactivity for yellow fluorescent protein in the dorsal funiculi and a defined region of each dorsal horn, and by counting immunoreactive axonal varicosities in the ventral horns. Two/three days post-lesion, the density of immunoreactivity in the dorsal horn contralateral to the lesion was reduced proportional to the decrease in positive fibres in the dorsal funiculus, however density of immunoreactive varicosities in the ventral horn was more resistant to loss. Over a three week period, immunoreactive axonal processes in the grey matter increased on the contralateral side, particularly in the ventral horn, but without an increase in immunopositive fibres in the contralateral dorsal funiculus, demonstrating sprouting of surviving immunoreactive fibres to replace lesioned corticospinal axons. However, the origin of sprouting fibres could not be identified with confidence as parallel observations revealed strongly immunoreactive neuronal cell bodies in the spinal cord, medulla and red nucleus. We have demonstrated plasticity in response to a developmental lesion but discovered a drawback to using these mice if visualisation of individual axons is enhanced by immunohistochemistry.

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