Corticostriatal plasticity is restricted by myelin‐associated neurite growth inhibitors in the adult rat

After unilateral cortical lesions in neonatal rats, the spared unablated hemisphere is known to demonstrate remarkable neuroanatomical plasticity in corticofugal connectivity. This same type of structural plasticity is not seen after similar lesions in adult rats. One possibility for the lack of such a plastic response in the adult central nervous system may be the presence of myelin‐associated neurite growth inhibitory proteins NI‐35/NI‐250. These proteins have previously been found to play a crucial role in preventing axotomized fibers from regenerating after adult rat spinal cord lesions. The aim of this study was to determine if blocking these inhibitory proteins by the application of the specific monoclonal antibody IN‐1 would enhance corticostriatal plasticity from the spared hemisphere after unilateral cortical lesions in adult rats. Six‐ to 8‐week‐old Lewis rats underwent unilateral aspiration lesion of the sensorimotor cortex. Animals were immediately treated with either monoclonal antibody IN‐1 or a control antibody released from hybridoma cells in Millipore filter capsules. After a survival period of 12 weeks, the opposite sensorimotor cortex was stereotaxically injected with the anterograde tracer biotinylated dextran amine, and biotinylated dextran amine–positive corticostriatal fibers were analyzed. The monoclonal antibody IN‐1–treated animals showed an increase in corticostriatal fibers in the dorsolateral striatum contralateral to the injection site compared with control antibody–treated animals or normal controls, indicating a specific sprouting response in the deafferented zone. These results support the idea that through blockade of myelin‐associated neurite inhibitory proteins, lesion‐induced corticofugal plasticity is possible even in the adult central nervous system. Ann Neurol 1999;45:778–786

[1]  P. S. Goldman,et al.  Prenatal removal of frontal association cortex in the fetal rhesus monkey: Anatomical and functional consequences in postnatal life , 1978, Brain Research.

[2]  J. Kapfhammer,et al.  Inverse patterns of myelination and GAP‐43 expression in the adult CNS: Neurite growth inhibitors as regulators of neuronal plasticity? , 1994, The Journal of comparative neurology.

[3]  P. S. Goldman.  Neuronal plasticity in primate telencephalon: anomalous projections induced by prenatal removal of frontal cortex. , 1978, Science.

[4]  M F Chesselet,et al.  Anatomical and functional evidence for lesion‐specific sprouting of corticostriatal input in the adult rat , 1996, The Journal of comparative neurology.

[5]  M. Wiesendanger,et al.  Trajectory of redirected corticospinal axons after unilateral lesion of the sensorimotor cortex in neonatal rat; A phaseolus vulgaris-leucoagglutinin (PHA-L) tracing study , 1991, Experimental Neurology.

[6]  C. Gilbert,et al.  Topographic reorganization in the striate cortex of the adult cat and monkey is cortically mediated , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[7]  C.J. Wilson,et al.  Morphology and synaptic connections of crossed corticostriatal neurons in the rat , 1987, The Journal of comparative neurology.

[8]  E. Neafsey,et al.  Electrophysiological analysis of motor cortical plasticity after cortical lesions in newborn rats , 1985, Brain Research.

[9]  E. Neafsey,et al.  Topography of corticopontine remodelling after cortical lesions in newborn rats , 1986, The Journal of comparative neurology.

[10]  C. Finch,et al.  Astrocytic messenger RNA responses to striatal deafferentation in male rat , 1993, Neuroscience.

[11]  R. Roberts,et al.  Evidence for synaptic proliferation, reorganization, and growth in the excitotoxic lesioned adult rat caudate nucleus , 1990, Experimental Neurology.

[12]  G. Schneider,et al.  Antibody neutralization of neurite growth inhibitors from oligodendrocytes results in expanded pattern of postnatally sprouting retinocollicular axons , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[13]  J. Donoghue,et al.  Neostriatal projections from individual cortical fields conform to histochemically distinct striatal compartments in the rat , 1986, Brain Research.

[14]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[15]  K. Kalil,et al.  Regrowth of severed axons in the neonatal central nervous system: establishment of normal connections. , 1979, Science.

[16]  M. Deschenes,et al.  Corticothalamic projections from layer V cells in rat are collaterals of long-range corticofugal axons , 1994, Brain Research.

[17]  M. Schwab,et al.  Degeneration and regeneration of axons in the lesioned spinal cord. , 1996, Physiological reviews.

[18]  Theresa A. Jones,et al.  Overgrowth and pruning of dendrites in adult rats recovering from neocortical damage , 1992, Brain Research.

[19]  H. Thoenen.  Neurotrophins and Neuronal Plasticity , 1995, Science.

[20]  A. Mcgeorge,et al.  The organization and collateralization of corticostriate neurones in the motor and sensory cortex of the rat brain , 1987, Brain Research.

[21]  M. Pisa.  Motor functions of the striatum in the rat: Critical role of the lateral region in tongue and forelimb reaching , 1988, Neuroscience.

[22]  S. Leong,et al.  Bilateral corticofugal projection to the red nucleus after neonatal lesions in the albino rat , 1976, Brain Research.

[23]  I. Divac,et al.  Prefrontal system in the rat visualized by means of labeled deoxyglucose—further evidence for functional heterogeneity of the neostriatum , 1980, The Journal of comparative neurology.

[24]  I. Whishaw,et al.  Sparing of skilled forelimb reaching and corticospinal projections after neonatal motor cortex removal or hemidecortication in the rat: support for the Kennard doctine , 1988, Brain Research.

[25]  S. Wise,et al.  The motor cortex of the rat: Cytoarchitecture and microstimulation mapping , 1982, The Journal of comparative neurology.

[26]  V L Towle,et al.  Functional magnetic resonance studies of the reorganization of the human hand sensorimotor area after unilateral brain injury in the perinatal period. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[27]  M. Schwab,et al.  Regeneration of lesioned rat optic nerve fibers is improved after neutralization of myelin-associated neurite growth inhibitors , 1994, Brain Research.

[28]  J. Villablanca,et al.  Novel crossed corticothalamic projections after neonatal cerebral hemispherectomy. A quantitative autoradiography study in cats , 1987, Brain Research.

[29]  M Hallett,et al.  Magnetic Stimulation of the Human Cerebral Cortex, an Indicator of Reorganization in Motor Pathways in Certain Pathological Conditions , 1991, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[30]  M. Schwab,et al.  Recovery from spinal cord injury mediated by antibodies to neurite growth inhibitors , 1995, Nature.

[31]  S. Iversen,et al.  Learning impairments following selective kainic acid-induced lesions within the neostriatum of rats , 1981, Behavioural Brain Research.

[32]  J. Kapfhammer,et al.  Increased Expression of the Growth‐associated Protein GAP‐43 in the Myelin‐free Rat Spinal Cord , 1994, The European journal of neuroscience.

[33]  C. D'amato,et al.  Motor-sensory and visual behavior after hemispherectomy in newborn and mature rats. , 1970, Experimental neurology.

[34]  M. Schwab,et al.  Regeneration of Lesioned Septohippocampal Acetylcholinesterase‐positive Axons is Improved by Antibodies Against the Myelin‐associated Neurite Growth Inhibitors NI‐35/250 , 1991, The European journal of neuroscience.

[35]  M. Schwab,et al.  Axonal regeneration in the rat spinal cord produced by an antibody against myelin-associated neurite growth inhibitors , 1990, Nature.

[36]  R. Lund,et al.  Anomalous bilateral corticofugal pathways in albino rats after neonatal lesions. , 1973, Brain research.

[37]  M. Schwab,et al.  Increased collateral sprouting of primary afferents in the myelin-free spinal cord , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[38]  L M Harrison,et al.  Patterns of central motor reorganization in hemiplegic cerebral palsy. , 1993, Brain : a journal of neurology.

[39]  D. Hillman,et al.  Robust synaptic plasticity of striatal cells following partial deafferentation , 1990, Brain Research.

[40]  M. Schwab,et al.  A role for oligodendrocytes in the stabilization of optic axon numbers , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[41]  A. Fagan,et al.  A Role for TrkA during Maturation of Striatal and Basal Forebrain Cholinergic Neurons In Vivo , 1997, The Journal of Neuroscience.

[42]  G. Schneider.  Early Lesions of Superior Colliculus: Factors Affecting the Formation of Abnormal Retinal Projections; pp. 91–109 , 1973 .

[43]  K. Kultas‐Ilinsky,et al.  Synaptic organization of motor corticostriatal projections in the rat , 1981, Experimental Neurology.

[44]  B. Kolb,et al.  Cortical and striatal structure and connectivity are altered by neonatal hemidecortication in rats , 1992, The Journal of comparative neurology.

[45]  M. Roger,et al.  Topographical organization of the projections from physiologically identified areas of the motor cortex to the striatum in the rat , 1992, Neuroscience Research.

[46]  G. Mihailoff,et al.  Corticopontine remodelling after cortical and/or cerebellar lesions in newborn rats , 1983, The Journal of comparative neurology.

[47]  R. Gainetdinov,et al.  Cocaine self-administration in dopamine-transporter knockout mice , 1998, Nature Neuroscience.

[48]  C. Leonard,et al.  The prefrontal cortex of the rat. I. Cortical projection of the mediodorsal nucleus. II. Efferent connections. , 1969, Brain research.

[49]  A. Castro,et al.  The effects of cortical ablations on digital usage in the rat. , 1972, Brain research.

[50]  J. Donoghue,et al.  A collateral pathway to the neostriatum from corticofugal neurons of the rat sensory‐motor cortex: An intracellular HRP study , 1981, The Journal of comparative neurology.

[51]  M. Schwab,et al.  Sprouting and Regeneration of Lesioned Corticospinal Tract Fibres in the Adult Rat Spinal Cord , 1993, The European journal of neuroscience.

[52]  M. E. Goldberger.  The Role Sprouting Might Play During the Recovery of Motor Function , 1981 .

[53]  C. Cotman,et al.  The Critical Afferent Theory: A Mechanism to Account for Septohippocampal Development and Plasticity , 1981 .

[54]  M. Chesselet,et al.  Expression of molecules associated with neuronal plasticity in the striatum after aspiration and thermocoagulatory lesions of the cerebral cortex in adult rats , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[55]  D O Frost,et al.  Plasticity of retinofugal projections after partial lesions of the retina in newborn syrian hamsters , 1979, The Journal of comparative neurology.

[56]  M. Schwab,et al.  Two membrane protein fractions from rat central myelin with inhibitory properties for neurite growth and fibroblast spreading , 1988, The Journal of cell biology.

[57]  A. Castro.  Ipsilateral corticospinal projections after large lesions of the cerebral hemisphere in neonatal rats , 1975, Experimental Neurology.

[58]  M. Schwab,et al.  Functional Recovery and Enhanced Corticofugal Plasticity after Unilateral Pyramidal Tract Lesion and Blockade of Myelin-Associated Neurite Growth Inhibitors in Adult Rats , 1998, The Journal of Neuroscience.

[59]  Yves-Alain Barde,et al.  Neurotrophin-3 enhances sprouting of corticospinal tract during development and after adult spinal cord lesion , 1994, Nature.