Trajectory of redirected corticospinal axons after unilateral lesion of the sensorimotor cortex in neonatal rat; a phaseolus vulgaris-leucoagglutinin (PHA-L) tracing study

The corticospinal neurons of the rat project almost exclusively to the contralateral spinal cord. Retrograde and anterograde tracing experiments showed that only about 2-4% of the corticospinal neurons of the sensorimotor cortex project to the ipsilateral spinal cord in the normal rat. The large majority of corticospinal axons (more than 90%) travel at spinal level at the base of the contralateral dorsal funiculus; in addition a few axons run in the contralateral lateral funiculus and at the base of the dorsal horn. The undecussated axons run in the ipsilateral dorsal (about 1-2%) and ventral (about 1-2%) funiculi. The rearrangement of the corticospinal projections was studied with various tracing methods in rats subjected to unilateral lesion of the sensorimotor cortex at Postnatal Day 2 to 4. Spinal injections of the tracer WGA-HRP that were restricted to the side opposite to the cortical lesion showed a significant increase of retrogradely labeled corticospinal neurons in the intact cortex as compared to the proportion of ipsilateral projections in control experiments. This was consistent with an increased density of anterogradely labeled corticospinal terminals in the spinal cord ipsilateral to an injection of WGA-HRP in the motor cortex opposite to neonatal lesion, in comparison to normal rats. The trajectory of these "aberrant" ipsilateral corticospinal projections resulting from the neonatal lesion of the opposite sensorimotor cortex was analyzed by means of the anterograde tracer phaseolus vulgaris-leucoagglutinin (PHA-L), injected in the motor cortex. These data indicated that decussated corticospinal axons recross at spinal levels, close to their terminal zone, where they appear to ramify and terminate in the spinal gray including the motoneurons. Such recrossing axons thus represent one new possible mechanism, among other previously reported ones, contributing to the increase of ipsilateral corticospinal projections in rats subjected to neonatal cortical lesion.     

Effects of changes in the periphery on development of the corticospinal motor system in the rat

Effects of changes in the periphery on development of the corticospinal (CS) motor system were studied in the rat. Unilateral forelimb restraint between ages 5 and 30 days resulted in an increase in the number of CS neurons which persisted in the adult. The effect was most marked ipsilateral to limb restraint where both crossed and uncrossed CS connections were increased, but it also occurred to a lesser extent on the contralateral side. Animals with limb restraint had enlargement of the areas of cerebral cortex in which CS neurons occurred. The enlargement of motor cortex regions and increase in CS neurons closely resembled the changes found in the remaining cerebral hemisphere after neonatal hemispherectomy. The findings in animals with forelimb restraint differed markedly from those after forelimb amputation, where little change occurred in either number or location of CS neurons. Limb restraint initiated at the time of postnatal hemispherectomy had no effects on location or number of CS neurons beyond those of hemispherectomy alone. It is proposed that transient CS axons that occur normally in the postnatal rat may be recruited for formation of permanent connections under very diverse conditions, i.e. hemispherectomy and limb restraint. Failure to observe an additional effect of limb restraint in hemispherectomized animals may be due to the fact that after hemispherectomy all available transient fibers in the remaining hemisphere are recruited for innervation of the side of the spinal cord that has lost its cortical input.     

Extensive spinal decussation and bilateral termination of cervical corticospinal projections in rhesus monkeys

To examine neuroanatomical mechanisms underlying fine motor control of the primate hand, adult rhesus monkeys underwent injections of biotinylated dextran amine (BDA) into the right motor cortex. Spinal axonal anatomy was examined using detailed serial‐section reconstruction and modified stereological quantification. Eighty‐seven percent of corticospinal tract (CST) axons decussated in the medullary pyramids and descended through the contralateral dorsolateral tract of the spinal cord. Eleven percent of CST axons projected through the dorsolateral CST ipsilateral to the hemisphere of origin, and 2% of axons projected through the ipsilateral ventromedial CST. Notably, corticospinal axons decussated extensively across the spinal cord midline. Remarkably, nearly 2‐fold more CST axons decussated across the cervical spinal cord midline (≈12,000 axons) than were labeled in all descending components of the CST (≈6,700 axons). These findings suggest that CST axons extend multiple segmental collaterals. Furthermore, serial‐section reconstructions revealed that individual axons descending in either the ipsilateral or contralateral dorsolateral CST can: 1) terminate in the gray matter ipsilateral to the hemisphere of origin; 2) terminate in the gray matter contralateral to the hemisphere of origin; or 3) branch in the spinal cord and terminate on both sides of the spinal cord. These results reveal a previously unappreciated degree of bilaterality and complexity of corticospinal projections in the primate spinal cord. This bilaterality is more extensive than that of the rat CST, and may resemble human CST organization. Thus, augmentation of sprouting of these extensive bilateral CST projections may provide a novel target for enhancing recovery after spinal cord injury. J. Comp. Neurol. 513:151–163, 2009. © 2009 Wiley‐Liss, Inc.     

Bilateral corticospinal projections arise from each motor cortex in the macaque monkey: a quantitative study

The corticospinal projection is considered to influence fine motor function through nearly exclusively contralateral projections from the cortex in primates. However, unilateral lesions to this system in various species are frequently followed by significant functional improvement, raising the possibility that bilateral projections of this pathway may exist or emerge after injury. To examine the detailed anatomy and projections of the corticospinal motor neurons in rhesus monkeys (n = 4), we injected the high-resolution anterograde tracer biotinylated dextran amine (BDA) into 126 sites centered about the right lower extremity (LE) primary motor cortex. Projection and termination patterns were quantified at lumbar levels L1, L4, and L7 and mapped by using serial-section reconstructions. Notably, a mean of 10.1 +/- 0.6% (+/- SEM) of corticospinal tract (CST) axons descended in the lateral CST ipsilateral to the cortical BDA injection, and 87.9 +/- 1.0% of total CST axons projected in the contralateral lateral CST. The ipsilateral ventral CST contained only 1.0 +/- 0% of all projecting CST axons, whereas the contralateral ventral CST contained 0.3 +/- 0.2% of all axons. In addition, a minor dorsal column CST projection was identified. Measurement of BDA-labeled terminals in the spinal cord gray matter revealed that 11.2 +/- 2.2% of CST axons terminated ipsilateral to the side of cortical injection, and the remainder terminated contralaterally. As previously reported, most CST axons terminated in spinal cord laminae V-VIII, as well as the laterodorsal motoneuronal group of lamina IX (which innervates distal extremity muscles). Notably, many CST axons crossed the spinal cord midline (mean 19.9 +/- 4.9 axons per 40-microm-thick section). Detailed single-axon reconstructions revealed that most ipsilaterally projecting lateral CST axons terminated in ipsilateral gray matter. Notably, we found that the bouton-like swellings of many ipsilateral CST axons descending in the dorsolateral tract were located within Rexed's lamina IX, in close proximity to motoneuronal somata. Thus, bilateral projections of corticospinal axons originating from a single motor cortex could contribute to bilateral control of spinal motor neurons and to the highly evolved degree of fine motor control in primates. Furthermore, bilateral CST projections from a single motor cortex could represent a potential source of plasticity after injury, as well as a target of therapeutic effort in neural regeneration strategies.     

Corticospinal tract development and its plasticity after perinatal injury

The final pattern of the origin and termination of the corticospinal tract is shaped during development by the balance between projection and withdrawal of axons. In animals, unilateral inhibition of the sensorimotor cortex during development results in a sparse contralateral projection from this cortex and retention of a greater number of ipsilateral projections from the more active cortex. Similarly in subjects with hemiplegic cerebral palsy if transcranial magnetic stimulation (TMS) of the damaged motor cortex fails to evoke responses in the paretic upper limb, TMS of the undamaged ipsilateral motor cortex evokes abnormally large and short-onset responses. Rather than representing a “reparative plasticity in response to injury”, this review presents evidence that increased ipsilateral projections from the non-infarcted motor cortex arise from perturbation of ongoing developmental processes, whereby reduced activity in the damaged hemipshere, leads to increased withdrawal of its surviving contralateral corticospinal projections because their terminals have been displaced by the more active ipsilateral projections of the undamaged hemisphere and thereby adding to the degree of long-term motor impairment.     

Evidence of activity-dependent withdrawal of corticospinal projections during human development.

OBJECTIVE: To characterize the development of ipsilateral corticospinal projections from birth and compare to 1) development of contralateral projections in the same subjects and 2) ipsilateral corticospinal projections in subjects with unilateral lesions of the corticospinal system acquired perinatally or in adulthood. METHOD: Transcranial magnetic stimulation excited the motor cortex, and responses were recorded bilaterally in pectoralis major, biceps brachii, and the first dorsal interosseus muscles. Subjects studied included 9 neonates recruited at birth, studied longitudinally for 2 years; 85 healthy subjects aged from birth to adulthood; 10 subjects with hemiplegic cerebral palsy; and 8 with hemiplegia after stroke. RESULTS: In neonates, ipsilateral responses had significantly shorter onsets than contralateral responses but similar thresholds and amplitudes. Thresholds within both pathways increased in the first 3 months. Differential development was present from 3 months so that by 18 months ipsilateral responses were significantly smaller and had significantly higher thresholds and longer onset latencies than contralateral responses. A similar pattern of smaller and later ipsilateral responses was observed after transcranial magnetic stimulation of the intact cortex in subjects with stroke. In contrast, subjects with hemiplegic cerebral palsy had ipsilateral responses with onsets, thresholds and amplitudes similar to those of contralateral responses. Significant branching of contralateral corticospinal axons from the intact motor cortex was excluded by cross-correlation analysis. CONCLUSIONS: These data, together with previously published anatomic and radiologic studies, are consistent with activity-dependent corticospinal axonal withdrawal during development and maintenance of increased corticomotoneuronal projections from the intact hemisphere after unilateral perinatal lesions.     

A retrograde tracing study of compensatory corticospinal projections in rats with neonatal hemidecortication

To examine the compensatory mechanisms in rats that underwent left decortication at postnatal day 7 (P7), we injected the retrograde tracers fluorescein isothiocyanate-cholera toxin B subunit (FITC-CTB) and Fast Blue (FB) into the right and left upper cervical spinal cord, respectively, at postoperative weeks 2, 3, 4, and 5 and counted the number of retrogradely labeled corticospinal neurons in the right cerebral cortex compared with that in normally developed rats. Significantly more ipsilaterally projecting neurons were labeled with FITC-CTB in the decorticated rats compared with normal rats at all time points examined. The number of labeled neurons was similar to that at P7 in normal rats. There were also some FITC-CTB and FB double-labeled neurons in both decorticated and normal rats. The number of double-labeled neurons in the decorticated rats increased each week and was significantly greater than that in normal rats at postoperative weeks 4 and 5. The present results suggest that the elimination of ipsilaterally projecting axons observed in normal rats was prevented in the decorticated rats, so that the cerebral cortex neurons on the unlesioned side projected corticospinal tracts to the ipsilateral spinal cord. Furthermore, the collaterals of the corticospinal tracts originating from the cerebral cortex on the unlesioned side also project to the ipsilateral spinal cord. These compensatory mechanisms might underlie the acquisition of motor function in these animals.     

Redirected growth of pyramidal tract axons following neonatal pyramidotomy in cats

After the pyramidal tract at the pontomedullary junction in neonatal cats had been cut and the ipsilateral frontoparietal cortex injected with intra-axonal markers at 40 to 74 days of age, cortical axons were labeled in aberrant pathways that descended into the caudal medulla and spinal cord. Some labeled axons from the damaged pyramidal tract crossed the midline, descended with fibers in the intact pyramidal tract through the pyramidal decussation, and entered the lateral corticospinal tract. Another group of aberrant projections descended bilaterally along the ventrolateral edge of the medulla and either ended in the lateral reticular nuclei or continued into the spinal cord. Finally, some axons descended individually through the central medullary tegmentum and ended bilaterally in the spinal trigeminal, dorsal column, and lateral reticular nuclei. Although these findings suggest that pyramidal tract axons regenerate after injury, the findings from a second series of experiments refute this conclusion. In 2- to 5-day-old cats, the fluorescent dye Fast Blue was injected into the spinal cord, and 7 to 8 days later the contralateral pyramidal tract was cut. In these animals, there were never any cortical neurons retrogradely labeled with Fast Blue in the frontoparietal cortex ipsilateral to the pyramidotomy, although numerous neurons were labeled contralaterally. Control experiments confirmed that the interval between the Fast Blue injections and the pyramidotomies was long enough for retrogradely labeling cortical neurons, that the spinal cord injections did not adversely affect the retrogradely labeled cortical neurons, and following axotomy dying cortical neurons could be demonstrated directly using silver impregnation techniques. We conclude that neonatal pyramidotomy causes the death of all axotomized cortical neurons in kittens, and, therefore, the aberrant cortical projections seen caudal to the lesion must be redirected, late-developing, and undamaged cortical axons, and not regenerated axons.     

Regeneration of corticospinal axons in the rat.

In the rat, a few long descending motor tracts capable of carrying an impulse and causing a propagated impulse in the ipsilateral sciatic nerve will regenerate after complete spinal cord transection. In this experiment such regeneration was found in both treated and control animals. Orthograde axonal transport of tritiated proline injected into the motor cortex labels only the corticospinal tracts in the rat spinal cord. Scintillation counts of measured lengths of spinal cord can be used as a measure of the number of labeled corticospinal axons. Comparison of radioactivity per unit length of measured cord segments taken from above and below the site of a previous spinal cord transection can give a reliable estimate of the number of labeled axons that regenerated and crossed the site of injury. Using this test we have demonstrated that some corticospinal axons had regenerated six months after spinlal cord transection in control animals, animals made tolerant to degenerating spinal cord antigens, and animals treated with cyclophosphamide. A group treated with a single 75 mg per kilogram dose of cyclophosphamide 24 hours after spinal cord transection showed the best evidence of corticospinal tract regeneration.     

Development and malformations of the human pyramidal tract

Abstract The corticospinal tract develops over a rather long period of time, during which malformations involving this main central motor pathway may occur. In rodents, the spinal outgrowth of the corticospinal tract occurs entirely postnatally, but in primates largely prenatally. In mice, an increasing number of genes have been found to play a role during the development of the pyramidal tract. In experimentally studied mammals, initially a much larger part of the cerebral cortex sends axons to the spinal cord, and the site of termination of corticospinal fibers in the spinal grey matter is much more extensive than in adult animals. Selective elimination of the transient corticospinal projections yields the mature projections functionally appropriate for the pyramidal tract. Direct corticomotoneuronal projections arise as the latest components of the corticospinal system. The subsequent myelination of the pyramidal tract is a slow process, taking place over a considerable period of time. Available data suggest that in man the pyramidal tract develops in a similar way. Several variations in the funicular trajectory of the human pyramidal tract have been described in otherwise normally developed cases, the most obvious being those with uncrossed pyramidal tracts.A survey of the neuropathological and clinical literature, illustrated with autopsy cases, reveals that the pyramidal tract may be involved in a large number of developmental disorders. Most of these malformations form part of a broad spectrum, ranging from disorders of patterning, neurogenesis and neuronal migration of the cerebral cortex to hypoxic-ischemic injury of the white matter. In some cases, pyramidal tract malformations may be due to abnormal axon guidance mechanisms. The molecular nature of such disorders is only beginning to be revealed.     

Absence of impairments or recovery mediated by the uncrossed pyramidal tract in the rat versus enduring deficits produced by the crossed pyramidal tract

The pyramidal tract of the rat consists of at least two components. A majority of the fibers cross in the lower medulla and descend through the spinal cord in the ventral portion of the dorsal funiculus. The remaining 5% of the corticospinal projection does not cross and descends in the ipsilateral ventral funiculus into the cervical spinal region where its projections terminate in the internuncial portions of the spinal gray matter. The anatomical origin and terminal distribution of the ipsilateral component suggests that it may be involved in the control of the ipsilateral limb, but the possible contribution of the ipsilateral corticospinal tract has not been systematically examined. To determine whether the ipsilateral corticospinal tract makes a contribution to skilled movement, the corticospinal tract was severed unilaterally at the medullary level rostral to the decussation, thus severing both the crossed component of the tract as well as the ipsilateral component. Performance of the ipsilateral and the contralateral limbs of rats were then evaluated on tests of limb posture, preference, placing, and use in two skilled reaching tasks. No impairments on any quantitative or qualitative measure of performance were detected in the use of the limb ipsilateral to the lesion but severe, enduring impairments on all qualitative and quantitative measures were obtained in use of the limb contralateral to the lesion. Thus, the study finds: (1) no evidence that the ipsilateral portion of the corticospinal tract makes a contribution to skilled movement of the kind made by the contralateral portion of the corticospinal tract, and (2) no evidence that the remaining uncrossed portion of the tract contributes to recovery of symptoms produced by severing the crossed portion of the tract.     

Neurophysiology of unimanual motor control and mirror movements.

In humans, execution of unimanual motor tasks requires a neural network that is capable of restricting neuronal motor output activity to the primary motor cortex (M1) contralateral to the voluntary movement by counteracting the default propensity to produce mirror-symmetrical bimanual movements. The motor command is transmitted from the M1 to the contralateral spinal motoneurons by a largely crossed system of fast-conducting corticospinal neurons. Alteration or even transient dysfunction of the neural circuits underlying movement lateralization may result in involuntary mirror movements (MM). Different models exist, which have attributed MM to unintended motor output from the M1 ipsilateral to the voluntary movement, functionally active uncrossed corticospinal projections, or on a combination of both. Over the last two decades, transcranial magnetic stimulation (TMS) proved as a valuable, non-invasive neurophysiological tool to investigate motor control in healthy volunteers and neurological patients. The contribution of TMS and other non-invasive electrophysiological techniques to characterize the neural network responsible for the so-called 'non-mirror transformation' of motor programs and the various mechanisms underlying 'physiological' mirroring, and congenital or acquired pathological MM are the focus of this review.     

Spinocerebellar projections to the vermis of the posterior lobe and the paramedian lobule in the cat,as studied by retrograde transport of horseradish peroxidase

Spinal neurons projecting to the posterior lobe of the cerebellum were identified with the retrograde horseradish peroxidase technique in the cat. In four cases with the injections, which were preceded by hemisections at cervical or thoracic levels, it was determined whether in the spinal cord the identified neurons give rise to crossed ascending axons or uncrossed ascending ones. The main groups of neurons projecting to sublobule VIIIB were located in the central cervical nucleus (with crossed ascending axons), Clarke's column (with uncrossed ascending axons), and the medial part of lamina VII of L6 to the caudal segments (with crossed ascending axons). Additional labeled neurons were found in the medial part of lamina VI between C2 and T1 and of L5 and L6 (with uncrossed ascending axons), and in the ventral as well as dorsal horns of the sacral-caudal segments (with crossed ascending axons). On the other hand, neurons projecting to sublobule C (the copular part) of the paramedian lobule, which appeared always ipsilaterally to the side of the injections, were located in lamina V of C8 to L4 (with uncrossed ascending axons). Marginal neurons of Clarke's column (with uncrossed ascending axons) and spinal border cells (with crossed ascending axons that recross in the cerebellum) projected specifically to this part. At L1 and L2 or L2 and L3 labeled large and medium-sized neurons were also found within Clarke's column. The present study suggests that there are segregated projections of spinal neurons to the cortex of the cerebellar posterior lobe.     

Distinct lateral and medial projections of the spinohypothalamic tract of the rat

We recently described a direct nociceptive projection from the spinal cord to the hypothalamus in the rat. Several electrophysiological studies of this projection indicated that the axons of some spinohypothalamic tract neurons (SHT) reach the hypothalamus either by a lateral or by a medial route. The purpose of this study was to determine the origin of all SHT neurons that reach the hypothalamus through the lateral and the medial projections, and to investigate the possibility of ablating the SHT without damaging other important sensory and motor tracts by combining retrograde tracing techniques with axonal ablation. As compared with control cases, significant (P < .05) reductions in the number of labeled SHT neurons were encountered, 26% in the ipsilateral spinal cord following lesions of the medial projection, 67% in the contralateral spinal cord following lesions of the lateral projection, and 94% in both contra- and ipsilateral sides following lesions of both the medial and lateral projections. Bilateral lesions of the lateral projections had no effect on the distribution of labeled neurons in the spinal cord and dorsal column nuclei following injections of Fluoro-Gold (FG) into the thalamus, and a small unilateral lesion of the lateral projection reduced the ipsilateral labeling in the motor cortex following injections of FG into the pyramidal decussation. These findings suggest that most SHT neurons ascend through the contralateral lateral projection and that less than half continue in the medial projection to the ipsilateral side. They also suggest a site that can be lesioned without affecting other ascending sensory spinal pathways. © 1996 Wiley-Liss, Inc.     

Reorganization of the corticospinal tract following neonatal unilateral cortical ablation in rats

The corticospinal tract in the rat after neonatal ablation of the unilateral cerebral cortex was studied morphologically and histochemically using the retrograde and antegrade horseradish peroxidase (HRP) tracing methods. The normal corticospinal tract in the lumbar cord was composed of a number of small and some large axons. In the atrophic corticospinal tract related to the ablated cerebral cortex, the small axons were decreased in number two weeks after the operation. However, new myelinated small axons appeared around day 28 and their diameters increased gradually from after day 56 to day 84. The original large axon in the atrophic corticospinal tract was much more increased in size than that in the corticospinal tract of the non-operated-on control. When HRP was injected into the left cervical cord of the adult rat whose right cerebral cortex had been ablated during the neonatal period, a considerable number of HRP-labeled neurons was seen in the healthy left cerebral cortex. When the corticospinal tract was traced antegradely by injecting HRP into the healthy left cerebral cortex, an aberrant corticospinal tract reaching into the ipsilateral dorsal funiculus was observed. These results give a morphological basis for the well known fact that children who have had brain damage during the neonatal period and early infancy have the capacity for recovery of motor function.     

A ventral uncrossed corticospinal tract in the rat

By studying cross-section autoradiograms of the spinal cord with dark field microscopy we demonstrated a ventral uncrossed corticospinal tract in the rat. Corticospinal fibers were labeled by the slow axoplasmic flow of a minute volume of high specific activity tritiated proline injected directly into the motor sensory cortex. The uncrossed ventral corticospinal tract was small but easily identifiable in the cervical region. More caudally the tract became less distinct and could not be traced below midthoracic levels. Only two corticospinal tracts were identified in this study: the well-known crossed dorsal corticospinal tract and the ventral uncrossed corticospinal tract described in this study.     

Changes in motor cortex activation after recovery from spinal cord inflammation.

Diseases of the spinal cord are associated with reactive changes in cerebral cortex organization. Many studies in this area have examined spinal cord conditions not associated with recovery, making it difficult to consider the value of these cortical events in the restoration of neurological function. We studied patients with myelitis, a syndrome of transient spinal cord inflammation, in order to probe cortical changes that might contribute to recovery after disease of the spinal cord. Seven patients, each of whom showed improvement in hand motor function after a diagnosis of myelitis involving cervical spinal cord, were clinically evaluated then studied with functional MRI. During right and left index finger tapping, activation volumes were assessed in three cortical motor regions within each hemisphere. Results were compared with findings in nine control subjects. Compared to the control group, myelitis patients had larger activation volumes within contralateral sensorimotor as well as contralateral premotor cortex. The degree of daily hand use showed a significant correlation with the volume of activation in contralateral sensorimotor cortex. Recovery from myelitis is associated with an enlarged activation volume in contralateral motor cortices. This change in motor cortex function is related to behavioral experience, and thus may contribute to motor improvement. The expanded activation in motor cortex, seen with several forms of spinal cord insult may have maximal utility when corticospinal tract axons are preserved.     

Dominance of ipsilateral corticospinal pathway in congenital mirror movements

OBJECTIVE: To clarify the mechanism of congenital mirror movements. DESIGN: The triple stimulation technique (TST) and the silent period were used to investigate a patient with congenital mirror movements. The TST was used to calculate the ratio of ipsilateral to contralateral corticospinal tracts from the two hemispheres to the spinal motor neurones. RESULTS: Transcranial magnetic stimulation over unilateral M1 induced larger ipsilateral than contralateral motor evoked potentials on both sides. Only 9% of spinal motor neurones innervating the abductor digitorum minimi were excited by contralateral primary motor cortex (M1) stimulation, while 94% were excited by the ipsilateral M1 stimulation. The silent period was examined during mirror movements and with voluntary contraction of the right first dorsal interosseus mimicking mirror movements. Left M1 stimulation (through the crossed corticospinal tract) did not show any difference in silent period between the two conditions, while right M1 stimulation (through the uncrossed tract) caused a longer silent period during mirror movements than during voluntary contractions. CONCLUSIONS: The results suggest that mirror movements may be caused by a strong connection between ipsilateral M1 and the mirror movements conveyed through a dominant ipsilateral corticospinal pathway.     

Cell death of corticospinal neurons is induced by axotomy before but not after innervation of spinal targets

The response of corticospinal neurons to axotomy at postnatal ages from 5 days to adulthood was studied in the golden hamster (Mesocricetus auratus). Corticospinal neurons were retrogradely labeled with fluorescent rhodamine latex beads injected into the cervical or lumbar spinal cord. A unilateral lesion of the medullary pyramidal tract was made 1-2 days later and the brains fixed 1-30 days after axotomy. Comparisons of labeled axotomized corticospinal neurons with labeled normal corticospinal neurons in the contralateral cortex showed that axotomy at 14 days or later caused cell shrinkage but not cell death. Axotomy prior to 14 days caused cell death of corticospinal neurons. More neurons died the earlier the lesion was made, culminating in virtual complete cell death of corticospinal neurons following axotomy at 5 days. Axotomy at a given age did not affect all corticospinal neurons uniformly. Lumbar projection neurons underwent cell death ranging from slight to complete following axotomy at 13 and 9 days, respectively. Cervical projection neurons, in contrast, survived axotomy after a lesion at 9 days but underwent complete cell death if the lesion occurred at 5 days. Since corticospinal axons innervate the cervical cord from postnatal days 4-8 and the lumbar cord from 10-14 days (Reh and Kalil, '81; J. Comp. Neurol. 200:55-67), the ability of corticospinal neurons to survive axotomy appears to be temporally well correlated with their innervation of spinal targets. These neurons die if their axons are cut prior to target innervation but are able to survive if axotomy occurs after their axons innervate spinal targets. The results show that plasticity in the corticospinal pathway documented in previous reports cannot take the form of regrowth of severed axons, since early lesions cause extensive corticospinal cell death. Aberrant corticospinal pathways resulting from early lesions must therefore arise from undamaged axons. Additional retrograde labeling experiments showed that the opposite cortex responded to contralateral pyramidotomy by sprouting into denervated areas of the spinal cord. Thus another source of plasticity after early pyramidal tract lesions is sprouting from corticospinal axons arising from the intact cortex.     

Synaptic targets of commissural interneurons in the lumbar spinal cord of neonatal rats

There is strong evidence that commissural interneurons, neurons with axons that extend to the contralateral side of the spinal cord, play an important role in the coordination of left/right alternation during locomotion. In this study we investigated the projections of commissural interneurons to motor neurons and other commissural interneurons on the other side of the spinal cord in neonatal rats. To establish whether there are direct contacts between axons of commissural interneurons and motor neurons, we carried out two series of experiments. In the first experiment we injected biotinylated dextran amine (BDA) into the lateral motor column to retrogradely label commissural interneurons that may have direct projections to motor neurons. Stained neurons were recovered in the ventromedial areas of the contralateral gray matter in substantial numbers. In the second experiment BDA was injected into the ventromedial gray matter on one side of the lumbar spinal cord, whereas motor neurons were simultaneously labeled on the opposite side by applying biocytin onto the ventral roots. BDA injections into the ventromedial gray matter labeled a strong axon bundle that arose from the site of injection, crossed the midline in the ventral commissure, and extensively arborized in the contralateral ventral gray matter. Many of these axons made close appositions with dendrites and somata of motor neurons and also with commissural interneurons retrogradely labeled with BDA. The results suggest that commissural interneurons may establish monosynaptic contacts with motor neurons on the opposite side of the spinal cord. Our findings also indicate that direct reciprocal connections between commissural interneurons on the two sides of the spinal cord may also exist.