Unilateral Cortical Ablation Research Articles

Molecular mechanisms of lesion-induced axonal sprouting in the corticofugal projection: the role of glial cells.

Molecular mechanisms of lesion-induced axonal sprouting in the corticofugal projection: the role of glial cells.

Involvement of Denervated Midbrain-Derived Factors in the Formation of Ectopic Cortico-Mesencephalic Projection after Hemispherectomy.

Neuronal remodeling after brain injury is essential for functional recovery. After unilateral cortical lesion, axons from the intact cortex ectopically project to the denervated midbrain, but the molecular mechanisms remain largely unknown. To address this issue, we examined gene expression profiles in denervated and intact mouse midbrains after hemispherectomy at early developmental stages using mice of either sex, when ectopic contralateral projection occurs robustly. The analysis showed that various axon growth-related genes were upregulated in the denervated midbrain, and most of these genes are reportedly expressed by glial cells. To identify the underlying molecules, the receptors for candidate upregulated molecules were knocked out in layer 5 projection neurons in the intact cortex, using the CRISPR/Cas9-mediated method, and axonal projection from the knocked-out cortical neurons was examined after hemispherectomy. We found that the ectopic projection was significantly reduced when integrin subunit β three or neurotrophic receptor tyrosine kinase 2 (also known as TrkB) was knocked out. Overall, the present study suggests that denervated midbrain-derived glial factors contribute to lesion-induced remodeling of the cortico-mesencephalic projection via these receptors.SIGNIFICANCE STATEMENT After brain injury, compensatory neural circuits are established that contribute to functional recovery. However, little is known about the intrinsic mechanism that underlies the injury-induced remodeling. We found that after unilateral cortical ablation expression of axon-growth promoting factors is elevated in the denervated midbrain and is involved in the formation of ectopic axonal projection from the intact cortex. Evidence further demonstrated that these factors are expressed by astrocytes and microglia, which are activated in the denervated midbrain. Thus, our present study provides a new insight into the mechanism of lesion-induced axonal remodeling and further therapeutic strategies after brain injury.

Sensory cortex lesion triggers compensatory neuronal plasticity

BackgroundLesions to the human brain often cause dramatic impairments in the life of patients because of the very limited capacity of the mammalian nervous system to regenerate. On the other hand, neuronal tissue has a high capacity to reorganize itself so that loss of function due to brain damage may be compensated through neuroplastic reorganization of undamaged tissue in brain regions adjacent or contralateral to the lesion site. In this study we investigated the effect of serial lesions of the auditory cortices (AC) in both hemispheres of Mongolian gerbils on discrimination performance for fast amplitude modulated tones (AM). Healthy animals were trained to discriminate two fast AM, an ability that has previously been shown to critically depend on cortical processing. Their ability to maintain significant discrimination performance was retested after unilateral AC lesion, and again after lesion of the contralateral AC, with 15 days of continuing training in between the two lesions.ResultsAfter bilateral cortical ablation of both AC and 45 days of training the animals show no change in pure tone detection threshold as measured with modulation of the acoustic startle reflex which has been shown to rely on subcortical structures. In contrast to simultaneous bilateral ablation of AC that results in complete loss of AM discrimination ability in this paradigm we found compensatory plasticity that seems to be triggered by unilateral cortical ablation with subsequent training and that is able to almost fully compensate for the lost cortical functions.ConclusionsOur results demonstrate that AM discrimination ability that normally depends on AC may be transferred to other brain regions when the brain has time to activate compensatory plasticity between the lesions of the two AC hemispheres. For this process to take place obviously one intact AC hemisphere is needed. This finding may open perspectives for new therapeutic strategies that may alleviate the impairments after multiple ischemic strokes.

Long‐term regulation in calretinin staining in the rat inferior colliculus after unilateral auditory cortical ablation

In this study we analyzed the effects in the inferior colliculus of a unilateral ablation of the auditory cortex in rats. Variations in both calretinin immunoreactivity and protein levels determined by Western blot suggest that such lesions induce changes in the regulation of this calcium-binding protein. Stereological counts of calretinin-immunoreactive neurons in the inferior colliculus 15, 90, and 180 days after the lesion showed a progressive increase in the number of immunoreactive neurons, with a parallel increase in the intensity of staining. Two hundred forty days after the cortical lesion, both the number of immunoreactive neurons and the staining intensity had returned to control values. The effects of the cortical lesion on calretinin regulation are more intense in those inferior colliculus subdivisions more densely innervated by the corticocollicular projection. This finding, along with the time course of calretinin regulation suggests that degeneration of the descending projection is linked to calretinin regulation in the inferior colliculus. We hypothesize, based on the role of calretinin, that the observed increase in immunoreactivity levels seen in the inferior colliculus after lesioning of the auditory cortex may be related to altered excitability in deafferented neurons. Our finding, may reflect adaptive mechanisms to changes in calcium influx and excitability in inferior colliculus neurons induced by lesions of the descending projection from the cortex to the inferior colliculus.

Contralesional neglect in monkeys with small unilateral parietal cortical ablations

Transient contralesional spatial neglect, in addition to motor impairment in the contralesional arm, is sometimes seen in patients following cerebral infarction in the right hemisphere and is seen following experimental occlusion of the right middle cerebral artery in primates. To test whether contralesional visuospatial neglect arises from a disruption of the forward flow of information from the striate cortex through the dorsal territory of the middle cerebral artery, we made a small strip suction ablation in the right parietal cortex from the medial edge of the dorsal cortical surface to the posterior ventral edge of the superior temporal gyrus in marmoset monkeys. These monkeys did not exhibit a motor impairment, or misreaching, with the contralesional arm. When they were unrestrained and free to use either arm, they were impaired at finding rewards in their contralesional space and in choosing the nearer of two rewards hidden in ipsilesional space (i.e. they had an ultra-ipsilesional bias in ipsilesional space). Comparison of performance under four conditions in a task in which the monkeys were constrained to reach into each hemispace with each arm separately indicated that they were impaired at reaching into contralesional, but not ipsilesional, space with either arm but they did not exhibit any impairment confined to the contralesional arm. These impairments in contralesional space were transient suggesting that the monkeys were able to re-align their egocentric spatial coordinates to obviate these deficits.

Ibotenic acid lesions in the pedunculopontine region result in recovery of visual orienting in the hemianopic cat

Cats rendered hemianopic by a unilateral visual cortical ablation can recover the visual orienting response in the hemianopic visual field following disruption of the caudal non-tectotectal containing half of the commissure of the superior colliculus. Ibotenic acid lesions of a small ‘critical zone’ in the contralateral substantia nigra result in a similar recovery effect. A conceptual framework developed by Wallace et al. (1990) [J. Comp. Neurol. 296, 222–252] proposed that elimination of contralateral substantia nigra ‘critical zone’ inhibition on the superior colliculus ipsilateral to a visual cortical lesion is responsible for the recovery. This model is insufficient, however, to explain the observation that hemi-decorticate cats with contralateral substantia nigra ‘critical zone’ lesions which include but extend beyond the ‘critical zone’ do not demonstrate the recovery. In these cats, subsequent transection of the commissure of the superior colliculus does lead to the recovery. We hypothesize that another projection through the caudal commissure of the superior colliculus, from the pedunculopontine nucleus, is involved in the recovery effect. Visual orienting behavior was recorded before and after ibotenic acid lesions made in the pedunculopontine nucleus region contralateral to a visual cortical ablation in 16 cats. Four cats with lesions in a small rostral region of the contralateral pedunculopontine nucleus recovered the visual orienting response in the previously hemianopic visual field. Contralateral tectal projections from the pedunculopontine nucleus are thought to be cholinergic and terminate as distinct patches in the intermediate gray layers of the superior colliculus. Since this region of the pedunculopontine nucleus also receives GABA-ergic afferents from the substantia nigra, we propose that a subcortical neural circuit including the substantia nigra, pedunculopontine nucleus, and superior colliculus is involved in the recovery of visual orienting.

Alleviation of brain injury-induced cerebral metabolic depression by amphetamine: a cytochrome oxidase histochemistry study.

Measurements of oxidative metabolic capacity following the ablation of rat sensorimotor cortex and ,he administration of amphetamine were examined to determine their effects on the metabolic dysfunction that follows brain injury. Twenty-four hours after surgery, rats sustaining either sham operations or unilateral cortical ablation were administered a single injection of D-amphetamine (2 mg/kg; i.p.) or saline and then sacrificed 24 h later. Brain tissue was processed for cytochrome oxidase histochemistry, and 12 bilateral cerebral areas were measured, using optical density as an index of the relative amounts of the enzyme. Compared with that of the control groups, cytochrome oxidase in the injured animals was significantly reduced throughout the cerebral cortex and in 5 of II subcortical structures. This injury-induced depression of oxidative capacity was most pronounced in regions of the hemisphere ipsilateral to the ablation. Animals given D-amphetamine had less depression of oxidative capacity, which was most pronounced bilaterally in the cerebral cortex, red nucleus, and superior colliculus; and in the nucleus accumbens, caudateputamen, and globus pallidus ipsilaterai to the ablation. The ability of D-amphetamine to alleviate depressed cerebral oxidative metabolism following cortical injury may be one mechanism by which drugs increasing noradrenaline release accelerate functional recovery in both animals and humans.

Differential regulation of the growth-associated proteins, GAP-43 and SCG-10, in response to unilateral cortical ablation in adult rats

Synapse replacement after brain injury has been widely documented by anatomical studies in various parts of both the developing and adult nervous system. However, the molecular events that define the specificity of the empirically derived rules of reactive synaptogenesis in different regions of the adult brain remain unclear. In this study we examined the differential regulation of the lesion-induced response of the two growth-associated proteins, superior cervical ganglia-10 and growth-associated protein-43, after unilateral cortex ablation, and determined a hierarchical order for the lesion response from remaining afferent projection neurons originating from the contralateral cortex, ipsilateral thalamus and substantia nigra. We report that in response to unilateral cortex ablation both messenger RNA, by northern blot, and protein, by estern blot, for superior cervical ganglia-10 but not growth-associated protein-43 was increased in the homologous area of the contralateral cortex but not the ipsilateral thalamus or substantia nigra. In addition, the specificity of the superior cervical ganglia-10 response, assessed by combined in situ hybridization and retrograde FluoroGold labeling of striatal afferent neurons, found that superior cervical ganglia-10 messenger RNA was increased prominently in layer V pyramidal neurons of the contralateral corticostriatal pathway but was unchanged in afferent projection neurons from the thalamus and substantia nigra. Furthermore, the increase in both superior cervical ganglia-10 messenger RNA and protein seen at three days postlesion in contralateral corticostriatal neurons coincides in time with the initiation of neurite outgrowth in the deafferented striatum by contralateral corticostriatal axons described in our previous ultrastructural study. However, if cortical input to the striatum was removed bilaterally the lesion-induced response for superior cervical ganglia-10 messenger RNA shifted secondarily to thalamostriatal neurons in the ipsilateral thalamus. These data provide evidence that superior cervical ganglia-10 and growth-associated protein-43 are differentially regulated in neurons of the contralateral corticostriatal pathway in response to unilateral cortex ablation and suggests that superior cervical ganglia-10 plays a role in the regulation of neurite outgrowth in the adult striatum after brain injury. However, the specific role that superior cervical ganglia-10 may play in reactive synaptogenesis remains unclear. In addition, our data suggest that a hierarchical order exists for the reinnervation of deafferented striatal neurons after unilateral cortex ablation with preference given to homologous axons from the contralateral cortex.

Two modes of corticospinal reinnervation occur close to spinal targets following unilateral lesion of the motor cortex in neonatal hamsters

Although it has been shown that unilateral neonatal cortical ablation induces bilateral corticospinal projections, the explanation for the pathways responsible for this bilateral innervation remains controversial. We hypothesized that such reinnervation may be supplied from newly formed fibers sprouting at the level rostral to, or at, or caudal to the pyramidal decussation. In order to test our hypothesis, we examined the brain and spinal cord of young hamsters which had a unilateral ablation of the right motor cortex at six days postnatally, and then received an injection of an anterograde neuronal lectin tracer, Phaseolus vulgaris-leucoagglutinin, into the hindlimb area of the left motor cortex at 21 days postnatally. For the identification of motoneurons in the lumbar spinal cord, some of these animals also received an injection of cholera toxin subunit B, a retrograde tracer, into the gastrocnemius muscle. A quantitative analysis in the left gray matter of the lumbar spinal cord indicated that the lectin labeling was two to eight times higher in cortically ablated animals than in intact animals. Immunohistochemical detection of the lectin revealed that innervation of the left spinal cord occurred close to targets at lower levels in the spinal cord. Two modes of reinnervation (types I and II) by the intact corticospinal tract were recognized. The type I fibers consisted of recrossing axon collaterals sprouted from the intact dorsal funiculus near their targets, while the type II fibers were recrossing parent axons which entered the intact, right gray matter several levels rostral to their targets, and then changed direction toward the targets. The recrossing at lower spinal levels yielded a large number of ipsilaterally labeled axons and their terminals in the gray matter of the denervated lumbar cord, with a distribution pattern similar to that seen on the intact side. The present results indicate that such ipsilateral innervation may play an important role in the sparing and recovery of function following neonatal hemicortical injury.

Ibotenic acid lesions of the substantia nigra pars reticulata ipsilateral to a visual cortical lesion fail to restore visual orienting responses in the cat

Unilateral removal of all known visual cortical areas in the cat renders the animal hemianopic in the contralateral visual field as measured by visual perimetry and other behavioral tests. We have shown that visual orientation behavior can be restored to the previously blind hemifield by destruction of a critical zone in the substantia nigra pars reticulata contralateral to a cortical lesion (Wallace et al., J. Comp. Neurol. 296:222-252, 1990). The model proposed to explain this recovery postulates that damage to the crossed nigrotectal projection disinhibits the superior colliculus ipsilateral to the cortical lesion and this leads to recovery. If disinhibition can account for recovery, then destruction of the uncrossed nigrotectal projection, which is known to exert a tonic inhibition on the superior colliculus, should also result in recovery. We made unilateral visual cortical ablations and ipsilateral ibotenic acid lesions of the substantia nigra pars reticulata. Visual orienting behavior was assessed in animals for a period of 4 to 31 weeks. Contrary to the prediction of the model, we failed to observe a recovery of visual orienting behavior in the blind hemifield in any of 23 animals.

Validation of a single-day Morris Water Maze procedure used to assess cognitive deficits associated with brain damage

This experiment was designed to validate a single-day Morris Water Maze procedure used to assess cognitive functioning in rats. Separate groups of randomly assigned rats received either bilateral or unilateral fimbria fornix transections, bilateral or unilateral cortical ablations, or a sham surgical control procedure. Subjects were tested 7 days postoperatively with a modified version of the Morris Water Maze procedure that requires only a single day of training. The results indicated that bilateral fimbria fornix transections severely disrupted acquisition. Unilateral fimbria fornix transections and bilateral and unilateral cortical lesions disrupted acquisition less severely but impaired subsequent test performance. In general, unilateral lesions of both types produced less severe deficits than bilateral lesions. The practical and analytical advantages of the single-day procedure are discussed.

Few neocortial and thalamic morphological changes after a neonatal frontal cortical ablation contrast with the effects of a similar lesion in fetal cats

To further understand the neuroanatomical consequences following perinatal brain injury, quantitative morphometric analysis was performed on the brain of cats receiving a unilateral frontal cortical ablation between postnatal days (P) 9 and P 14 and intact control cats. In all cats, the volume of the neocortex and thalamus was measured bilaterally and that of the thalamic ventrobasal complex (VBc) was measured ipsilaterally. In addition, using stereology, the neuronal and glial (presumably) cell packing densities (CPD) and the total number of neurons and glial cells (TCN) were measured in the ipsilateral VBc. The neuronal and glial cell coss-sectional areas (CSA) were also measured in the ipsilateral VBc. The mean ipsilateral and contralateral neocortex volumes were similar between the two animal groups. There was a statistically significant 14% and 13% reduction in mean ipsilateral and contralateral thalamic volumes, respectively for the lesioned animals, while the VBc shrank by 16% relative to intact controls. The mean neuronal and glial CPD were similar between the two groups. The mean neuronal TCN was reduced by 10% in the neonatal-lesioned cats, while the mean glial TCN was reduced by 31% in the same animals, however neither value reached significance. Lastly, the mean CSA of neurons and glial cells showed a tendency to be smaller in the lesioned cats by 8% and 9%, respectively. These results: (a) indicate that the neonatal lesion caused only minor morphological brain alterations and this sharply contrasts with the marked changes previously reported in cats with a similar lesion sustained prenatally; (b) suggest that the enhanced behavioral recovery and/or sparing reported for the present cats compared to fetal-lesioned animals is at least partially due to the morphological sparing reported here; (c) together with previous findings in fetal cats, support the hypothesis that the morphological changes after a neonatal neocortical lesion are qualitatively different and may depend on different mechanisms as compared to those occurring after similar damage sustained prenatally.

Mechanism on Formation of New Ipsilateral Corticospinal Tract Following Neonatal Unilateral Cortical Ablation in Rats

Mechanism on Formation of New Ipsilateral Corticospinal Tract Following Neonatal Unilateral Cortical Ablation in Rats

Glutamate receptor expression in rat striatum: Effect of deafferentation

The cerebral cortex is the primary source of glutamatergic afferents to the neostriatum. We used in situ hybridization to examine the effect of removal of the glutamatergic input to the striatum by unilateral frontal cortical ablation on the expression of genes encoding subunits from three families of glutamate receptors: N-methyl- d-aspartate receptors (NMDAR1, NMDAR2A, and NMDAR2B); α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors (GluR1-4, flip and flop splice variants); and metabotropic receptors (mGluR1-5). Significant changes were restricted to the dorsolateral quadrant of the ipsilateral striatum, the main projection area of the sensorimotor cortex. The expression of those messages which are normally abundant, NMDAR1, NMDAR2A, GluR1-4 flop and mGluR1, 3 and 5, was decreased in the deafferented dorsolateral striatum by 10–39% at 3 days after cortical ablation and subsequently increased to 120–165% of control at 15 and 60 days. mRNAs encoding the flip isoforms of GluR1-4, mGluR2 and 4, and an alternatively spliced region of NMDAR1 (Insertion I) which are undetectable or present at low levels in the striatum were not induced by cortical ablation. In contrast, both glial fibrillary acid protein and β-actin mRNA expression were markedly enhanced at 3 and 15 days, returning to near normal at 60 days. Striatal NMDA, AMPA and metabotropic type 1 ligand binding sites were increased as early as 3 days after cortical ablation, reached a peak at 15 days and remained increased for up to 60 days, while metabotropic type 2 binding was slightly but significantly reduced at 3 and 15 days and [ 3H]kainate binding did not change significantly. These results demonstrate that cortical ablation, and subsequent loss of glutamatergic afferents to the striatum, results in alterations in the expression of genes encoding glutamate receptor subunits in striatal neurons. The regulation of these genes appears to be coordinate, so that the relative abundance of the different messages is preserved.

Axon ramification following unilateral cortical ablation in neonatal rats

We confirmed the formation of an aberrant ipsilateral corticospinal tract after unilateral cerebral cortical ablation during the neonatal period in rat. This tract was studied using anterograde horseradish peroxidase (HRP) tracing. Ramifications of the axons in the pyramidal tract were found to contribute to the ipsilateral tract at the level of the pyramidal decussation, suggesting that ramification of immature axons plays an important role in the formation of the ipsilateral corticospinal tract.

Effect of unilateral motor cortex ablation on activity of choline acetyltransferase and levels of amino acid transmitter candidates in the spinal cord of adult monkeys

Evidence that L-glutamate is a neurotransmitter of corticofugal fibers was sought by measuring changes in several biochemical markers of neurotransmitter function in discrete regions of spinal cord after ablation of sensorimotor cortex in monkeys. One and five weeks after unilateral cortical ablation, samples from six areas of spinal cord (ventral, lateral and dorsal regions of the left and right sides) were analysed for choline acetyltransferase (ChAT) activity and contents of amino acid transmitter candidates-glutamic acid (Glu), aspartic acid (Asp), glycine (Gly), taurine (Tau) and gamma-aminobutyric acid (GABA). During one to five weeks after unilateral cortical ablation of the monkey, prolonged hemiplegia in the contralateral side was observed. Histological examination of the spinal cord 5 weeks after unilateral (left) cortical ablation showed no apparent change in either control (ipsilateral, left) or affected (contralateral, right) sides of the cord as examined by the Klüver-Barrera method. The ChAT activity as a cholinergic marker was scarcely changed in any region of either left (control) or right (affected) side of the spinal cord at one and five weeks after unilateral (left side) ablation of the motor cortex. Amino acid levels in each region of the spinal cord were not significantly changed one week after unilateral ablation of the motor cortex. However, a significant decrease of Glu content was observed in the lateral column of the affected (right) side compared to the control (left) side of cervical and lumbar cord five weeks after cortical ablation of the left motor area. No concomitant alterations of other amino acids were detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Transient enhancement of low-threshold calcium current in thalamic relay neurons after corticectomy

1. The alterations of voltage-sensitive calcium currents produced in thalamic cells by injury were investigated under voltage clamp using patch-clamp recordings in the whole-cell configuration. 2. One day after unilateral cortical ablation in immature rats (postnatal day 7), low-threshold transient calcium (T) currents in acutely isolated thalamic relay neurons (RNs) were increased by 68% compared with contralateral controls (P < 0.001). Three days after the operation, T currents in injured neurons were at 44% of control levels (P < 0.001). On the other hand, high-threshold (L) calcium currents in RNs did not change over the same interval. 3. To investigate the mechanism for the increase of T current, both kinetics and voltage dependency of activation and inactivation were examined. At a test voltage of -40 mV, the activation time constant decreased from 4.1 to 3.2 ms (P < 0.05); however, this small change was insufficient to explain the large increase in T current. Time constants for both fast and slow inactivation did not change significantly, nor did voltage dependence of activation or inactivation of thalamic T currents. 4. Methyl-phenyl-succinimide (MPS, 1 mM), a compound known to block T currents, was used to examine possible alterations in the pharmacological properties of T channels after injury. MPS was more effective in reducing T currents in normal versus injured RNs (24 and 20% reductions, respectively; P < 0.05), suggesting that pharmacological properties of T channels in the injured RNs may be different from those of the normal RNs.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of cortical ablation on apomorphine- and scopolamine-induced changes in dopamine turnover and ascorbic acid catabolism in the rat striatum

Levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), ascorbic acid and dehydroascorbic acid (DHAA) were measured by HPLC in the striatum of rats whose fronto-parietal cortex had been unilaterally ablated after a single injection of apomorphine (1 mg/kg s.c.), scopolamine (0.6 mg/kg s.c.) or L-glutamate (500 mg/kg i.p.). Unilateral cortical ablation decreased striatal levels of glutamate in both striata ipsilateral (35%) and contralateral (17–25%) to the lesion. Apomorphine and scopolamine significantly increased (+94 and +122%, respectively) the DHAA/ ascorbic acid ratio in the striata ipsilateral to the lesion in unoperated and sham-operated rats (+72 and +34%, respectively), but both drugs failed to increase it in ablated rats. L-Glutamate significantly increased the DHAA/ ascorbic acid ratio in unoperated (+53%) and ablated rats (+37%). The increase in sham-operated rats (+34%) did not reach statistical significance. Apomorphine and scopolamine significantly decreased the DOPAC/DA ratio in the striata ipsilateral to the lesion of unoperated, sham-operated and ablated rats. The decrease in the DOPAC/DA ratio induced only minor changes in striatal DA and DOPAC levels. We conclude that the apomorphine- and scopolamine-induced increase in ascorbic acid oxidation in the striatum requires intact cortico-striatal glutamatergic pathways. Cortical ablation potentiates the apomorphine- and scopolamine-induced inhibition of striatal DA turnover.

Asymmetric increase in substance P immunoreactivity in the rat and guinea pig substantia nigra after unilateral neocortical ablation

Substance P was visualized in the rat and the guine pig basal ganglia, mesencephalon and spinal cord after surgical unilateral cortical ablation. An increased density in substance P-like immunoreactive patterns in the substantia nigra was observed ipsilaterally to the lesioned hemisphere. These results, together with previous observations in cases of Alzheimer's disease presenting with asymmetric cortical atrophy, suggest an influence of the corticostriatal pathway on substance P-like immunoreactivity in these subcortical structures. Finally, these experiments proved to be a reliable animal model for the study of the effects of neocortical lesions on the neuropeptidergic innervation of certain subcortical regions.

Formation of an ipsilateral corticospinal tract after ablation of cerebral cortex in neonatal rat

The formation of an aberrant ipsilateral corticospinal tract after unilateral cerebral cortical ablation during the neonatal period has been confirmed in the rat. The tract was chronologically studied using the antegrade horseradish peroxidase (HRP) tracing method. An aberrant ipsilateral tract is not observed 3 days after the operation. However, ipsilateral HRP positive fibers become apparent on day 7 and progressively more prominent until day 14. These results suggest that the ipsilateral corticospinal tract is composed of collateral axons originating from pyramidal neurons in the healthy ipsilateral cerebral cortex. These results also indicate that, when cerebral cortex has the damage during early postnatal life, the remaining cortical neurons which have been freed from the damage show considerable plasticity in terms of the collateral axons.