Skip to main content
NeuroRx logoLink to NeuroRx
. 2012 Sep 5;3(4):420–427. doi: 10.1016/j.nurx.2006.07.006

Plasticity

Randolph J Nudo 1,
PMCID: PMC3593404  PMID: 17012055

Summary

Over the past 20 years, evidence has mounted regarding the capacity of the central nervous system to alter its structure and function throughout life. Injury to the central nervous system appears to be a particularly potent trigger for plastic mechanisms to be elicited. Following focal injury, widespread neurophysiological and neuroanatomical changes occur both in the peri-infarct region, as well as throughout the ipsi- and contralesional cortex, in a complex, time-dependent cascade. Since such post-injury plasticity can be both adaptive or maladaptive, current research is directed at understanding how plasticity may be modulated to develop more effective therapeutic interventions for neurological disorders, such as stroke. Behavioral training appears to be a significant contributor to adaptive plasticity after injury, providing a neuroscientific foundation for the development of physical therapeutic approaches. Adjuvant therapies, such as pharmacological agents and exogenous electrical stimulation, may provide a more receptive environment through which behavioral therapies may be imparted. This chapter reviews some of the recent results from animal models of injury and recovery that depict the complex time course of plasticity following cortical injury and implications for neurorehabilitation.

Key Words: plasticity, learning, stroke, brain repair, motor systems, cortex

References

  • 1.Butefisch CM, Davis BC, Wise SP, Sawaki L, Kopylev L, Classen J, Cohen LG. Mechanisms of use-dependent plasticity in the human motor cortex. Proc Natl Acad Sci USA. 2000;97:3661–3665. doi: 10.1073/pnas.97.7.3661. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Cheung SW, Nagarajan SS, Schreiner CE, Bedenbaugh PH, Wong A. Plasticity in primary auditory cortex of monkeys with altered vocal production. J Neurosci. 2005;25:2490–2503. doi: 10.1523/JNEUROSCI.5289-04.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Jones EG. Cortical and subcortical contributions to activity-dependent plasticity in primate somatosensory cortex. Annu Rev Neurosci. 2000;23:1–37. doi: 10.1146/annurev.neuro.23.1.1. [DOI] [PubMed] [Google Scholar]
  • 4.Kleim JA, Barbay S, Cooper NR, Hogg TM, Reidel CN, Remple MS, Nudo RJ. Motor learning-dependent synaptogenesis is localized to functionally reorganized motor cortex. Neurobiol Learn Mem. 2002;77:63–77. doi: 10.1006/nlme.2000.4004. [DOI] [PubMed] [Google Scholar]
  • 5.Meliza CD, Dan Y. Receptive-field modification in rat visual cortex induced by paired visual stimulation and single-cell spiking. Neuron. 2006;49:183–189. doi: 10.1016/j.neuron.2005.12.009. [DOI] [PubMed] [Google Scholar]
  • 6.Stettler DD, Yamahachi H, Li W, Denk W, Gilbert CD. Axons and synaptic boutons are highly dynamic in adult visual cortex. Neuron. 2006;49:877–887. doi: 10.1016/j.neuron.2006.02.018. [DOI] [PubMed] [Google Scholar]
  • 7.Diamond MC, Rosenzweig MR, Bennett EL, Lindner B, Lyon L. Effects of environmental enrichment and impoverishment on rat cerebral cortex. J Neurobiol. 1972;3:47–64. doi: 10.1002/neu.480030105. [DOI] [PubMed] [Google Scholar]
  • 8.Mohammed AH, Zhu SW, Darmopil S, Hjerling-Leffler J, Ern-fors P, Winblad B, Diamond MC, Eriksson PS, Bogdanovic N. Environmental enrichment and the brain. Prog Brain Res. 2002;138:109–133. doi: 10.1016/S0079-6123(02)38074-9. [DOI] [PubMed] [Google Scholar]
  • 9.Bennett EL, Diamond MC, Krech D, Rosenzweig MR. Chemical and anatomical plasticity of the brain. Science. 1964;146:610–619. doi: 10.1126/science.146.3644.610. [DOI] [PubMed] [Google Scholar]
  • 10.Kempermann G, Kuhn HG, Gage FH. Experience-induced neuro-genesis in the senescent dentate gyrus. J Neurosci. 1998;18:3206–3212. doi: 10.1523/JNEUROSCI.18-09-03206.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Rosenzweig MR, Bennett EL, Hebert M, Morimoto H. Social grouping cannot account for cerebral effects of enriched environments. Brain Res. 1978;153:563–576. doi: 10.1016/0006-8993(78)90340-2. [DOI] [PubMed] [Google Scholar]
  • 12.Jenkins WM, Merzenich MM, Ochs MT, Allard T, Guic-Robles E. Functional reorganization of primary somatosensory cortex in adult owl monkeys after behaviorally controlled tactile stimulation. J Neurophysiol. 1990;63:82–104. doi: 10.1152/jn.1990.63.1.82. [DOI] [PubMed] [Google Scholar]
  • 13.Clark SA, Allard T, Jenkins WM, Merzenich MM. Receptive fields in the body-surface map in adult cortex defined by temporally correlated inputs. Nature. 1988;332:444–445. doi: 10.1038/332444a0. [DOI] [PubMed] [Google Scholar]
  • 14.Buonomano DV, Merzenich MM. Associative synaptic plasticity in hippocampal cal neurons is not sensitive to unpaired presynaptic activity. J Neurophysiol. 1996;76:631–636. doi: 10.1152/jn.1996.76.1.631. [DOI] [PubMed] [Google Scholar]
  • 15.Sanes JN, Donoghue JP, Thangaraj V, Edelman RR, Warach S. Shared neural substrates controlling hand movements in human motor cortex. Science. 1995;268:1775–1777. doi: 10.1126/science.7792606. [DOI] [PubMed] [Google Scholar]
  • 16.Park MC, Belhaj-Saif A, Cheney PD. Properties of primary motor cortex output to forelimb muscles in rhesus macaques. J Neurophysiol. 2004;92:2968–2984. doi: 10.1152/jn.00649.2003. [DOI] [PubMed] [Google Scholar]
  • 17.Huntley GW, Jones EG. Relationship of intrinsic connections to forelimb movement representations in monkey motor cortex: A correlative anatomic and physiological study. J Neurophysiol. 1991;66:390–413. doi: 10.1152/jn.1991.66.2.390. [DOI] [PubMed] [Google Scholar]
  • 18.Stoney SD, Thompson WD, Asanuma H. Excitation of pyramidal tract cells by intracortical microstimulation: Effective extent of stimulating current. J Neurophysiol. 1968;31:659–669. doi: 10.1152/jn.1968.31.5.659. [DOI] [PubMed] [Google Scholar]
  • 19.Nudo RJ, Milliken GW, Jenkins WM, Merzenich MM. Use-dependent alterations of movement representations in primary motor cortex of adult squirrel monkeys. J Neurosci. 1996;16:785–807. doi: 10.1523/JNEUROSCI.16-02-00785.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Withers GS, Greenough WT. Reach training selectively alters dendritic branching in subpopulations of layer ii–iii pyramids in rat motor-somatosensory forelimb cortex. Neuropsychologia. 1989;27:61–69. doi: 10.1016/0028-3932(89)90090-0. [DOI] [PubMed] [Google Scholar]
  • 21.Plautz EJ, Milliken GW, Nudo RJ. Effects of repetitive motor training on movement representations in adult squirrel monkeys: Role of use versus learning. Neurobiol Learn Mem. 2000;74:27–55. doi: 10.1006/nlme.1999.3934. [DOI] [PubMed] [Google Scholar]
  • 22.Remple MS, Bruneau RM, VandenBerg PM, Goertzen C, Kleim JA. Sensitivity of cortical movement representations to motor experience: Evidence that skill learning but not strength training induces cortical reorganization. Behav Brain Res. 2001;123:133–141. doi: 10.1016/S0166-4328(01)00199-1. [DOI] [PubMed] [Google Scholar]
  • 23.Glees P, Cole J. Recovery of skilled motor functions after small repeated lesions in motor cortex in macaque. J Neurophysiol. 1950;13:137–148. [Google Scholar]
  • 24.Jenkins WM, Merzenich MMM. Reorganization of neocortical representations after brain injury: A neurophysiological model of the bases of recovery from Stroke. Prog Brain Res. 1987;71:249–266. doi: 10.1016/S0079-6123(08)61829-4. [DOI] [PubMed] [Google Scholar]
  • 25.Nudo RJ, Milliken GW. Reorganization of movement representations in primary motor cortex following focal ischemic infarcts in adult squirrel monkeys. J Neurophysiol. 1996;75:2144–2149. doi: 10.1152/jn.1996.75.5.2144. [DOI] [PubMed] [Google Scholar]
  • 26.Nudo RJ, Wise BM, SiFuentes F, Milliken GW. Neural substrates for the effects of rehabilitative training on motor recovery after ischemic infarct. Science. 1996;272:1791–1794. doi: 10.1126/science.272.5269.1791. [DOI] [PubMed] [Google Scholar]
  • 27.Stroemer RP, Kent TA, Hulsebosch CE. Neocortical neural sprouting, synaptogenesis, and behavioral recovery after neocortical infarction in rats. Stroke. 1995;26:2135–2144. doi: 10.1161/01.STR.26.11.2135. [DOI] [PubMed] [Google Scholar]
  • 28.Carmichael ST. Plasticity of cortical projections after Stroke. Neuroscientist. 2003;9:64–75. doi: 10.1177/1073858402239592. [DOI] [PubMed] [Google Scholar]
  • 29.Schiene K, Bruehl C, Zilles K, Qu M, Hagemann G, Kraemer M, Witte OW. Neuronal hyperexcitability and reduction of gabaa-receptor expression in the surround of cerebral photothrombosis. J Cereb Blood Flow Metab. 1996;16:906–914. doi: 10.1097/00004647-199609000-00014. [DOI] [PubMed] [Google Scholar]
  • 30.Carmichael ST. Cellular and molecular mechanisms of neural repair after stroke: Making waves. Ann Neurol. 2006;59:735–742. doi: 10.1002/ana.20845. [DOI] [PubMed] [Google Scholar]
  • 31.Kleim JA, Jones TA, Schallert T. Motor enrichment and the induction of plasticity before or after brain injury. Neurochem Res. 2003;28:1757–1769. doi: 10.1023/A:1026025408742. [DOI] [PubMed] [Google Scholar]
  • 32.Jones TA, Schallert T. Overgrowth and pruning of dendrites in adult rats recovering from neocortical damage. Brain Res. 1992;581:156–160. doi: 10.1016/0006-8993(92)90356-E. [DOI] [PubMed] [Google Scholar]
  • 33.Dum RP, Strick PL. Frontal lobe inputs to the digit representations of the motor areas on the lateral surface of the hemisphere. J Neurosci. 2005;25:1375–1386. doi: 10.1523/JNEUROSCI.3902-04.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Dancause N, Barbay S, Frost SB, Plautz EJ, Chen D, Zoubina EV, Stowe AM, Nudo RJ. Extensive cortical rewiring after brain injury. J Neurosci. 2005;25:10167–10179. doi: 10.1523/JNEUROSCI.3256-05.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Frost SB, Barbay S, Friel KM, Plautz EJ, Nudo RJ. Reorganization of remote cortical regions after ischemic brain injury: A potential substrate for stroke recovery. J Neurophysiol. 2003;89:3205–3214. doi: 10.1152/jn.01143.2002. [DOI] [PubMed] [Google Scholar]
  • 36.Dancause N, Barbay S, Frost SB, Plautz EJ, Stowe AM, Friel KM, Nudo RJ. Ipsilateral connections of the ventral premotor cortex in a new world primate. J Comp Neurol. 2006;495:374–390. doi: 10.1002/cne.20875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Friel KM, Barbay S, Frost SB, Plautz EJ, Hutchinson DM, Stowe AM, Dancause N, Zoubina EV, Quaney BM, Nudo RJ. Dissociation of sensorimotor deficits after rostral versus caudal lesions in the primary motor cortex hand representation. J Neurophysiol. 2005;94:1312–1324. doi: 10.1152/jn.01251.2004. [DOI] [PubMed] [Google Scholar]
  • 38.Taub E, Uswatte G, King DK, Morris D, Crago JE, Chatterjee A. A placebo-controlled trial of constraint-induced movement therapy for upper extremity after stroke. Stroke. 2006;37:1045–1049. doi: 10.1161/01.STR.0000206463.66461.97. [DOI] [PubMed] [Google Scholar]
  • 39.Sunderland A, Tuke A. Neuroplasticity, learning and recovery after stroke: A critical evaluation of constraint-induced therapy. Neuropsychol Rehabil. 2005;15:81–96. doi: 10.1080/09602010443000047. [DOI] [PubMed] [Google Scholar]
  • 40.Jones TA, Schallert T. Use-dependent growth of pyramidal neurons after neocortical damage. J Neurosci. 1994;14:2140–2152. doi: 10.1523/JNEUROSCI.14-04-02140.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.Bury SD, Adkins DL, Ishida JT, Kotzer CM, Eichhorn AC, Jones TA. Denervation facilitates neuronal growth in the motor cortex of rats in the presence of behavioral demand. Neurosci Lett. 2000;287:85–88. doi: 10.1016/S0304-3940(00)01138-1. [DOI] [PubMed] [Google Scholar]
  • 42.Adkins DL, Bury SD, Jones TA. Laminar-dependent dendritic spine alterations in the motor cortex of adult rats following callosal transection and forced forelimb use. Neurobiol Learn Mem. 2002;78:35–52. doi: 10.1006/nlme.2001.4045. [DOI] [PubMed] [Google Scholar]
  • 43.Jones TA, Chu CJ, Grande LA, Gregory AD. Motor skills training enhances lesion-induced structural plasticity in the motor cortex of adult rats. J Neurosci. 1999;19:10153–10163. doi: 10.1523/JNEUROSCI.19-22-10153.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.Biemaskie J, Corbett D. Enriched rehabilitative training promotes improved forelimb motor function and enhanced dendritic growth after focal ischemic injury. J Neurosci. 2001;21:5272–5280. doi: 10.1523/JNEUROSCI.21-14-05272.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.Kozlowski DA, James DC, Schallert T. Use-dependent exaggeration of neuronal injury after unilateral sensorimotor cortex lesions. J Neurosci. 1996;16:4776–4786. doi: 10.1523/JNEUROSCI.16-15-04776.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46.Humm JL, Kozlowski DA, Bland ST, James DC, Schallert T. Use-dependent exaggeration of brain injury: Is glutamate involved? Exp Neurol. 1999;157:349–358. doi: 10.1006/exnr.1999.7061. [DOI] [PubMed] [Google Scholar]
  • 47.Goldstein LB. Amphetamines and related drugs in motor recovery after Stroke. Phys Med Rehabil Clin N Am. 2003;14:S125–S134. doi: 10.1016/S1047-9651(02)00060-8. [DOI] [PubMed] [Google Scholar]
  • 48.Feeney DM, Gonzalez A, Law WA. Amphetamine, haloperidol, and experience interact to affect rate of recovery after motor cortex injury. Science. 1982;217:855–857. doi: 10.1126/science.7100929. [DOI] [PubMed] [Google Scholar]
  • 49.Gladstone DJ, Danells CJ, Armesto A, McIlroy WE, Staines WR, Graham SJ, Herrmann N, Szalai JP, Black SE. Physiotherapy coupled with dextroamphetamine for rehabilitation after hemiparetic stroke: A randomized, double-blind, placebo-controlled trial. Stroke. 2006;37:179–185. doi: 10.1161/01.STR.0000195169.42447.78. [DOI] [PubMed] [Google Scholar]
  • 50.Platz T, Kim IH, Engel U, Pinkowski C, Eickhof C, Kutzner M. Amphetamine fails to facilitate motor performance and to enhance motor recovery among stroke patients with mild arm paresis: Interim analysis and termination of a double blind, randomised, placebo-controlled trial. Restor Neurol Neurosci. 2005;23:271–280. [PubMed] [Google Scholar]
  • 51.Barbay S, Zoubina EV, Dancause N, Frost SB, Eisner-Janowicz I, Stowe AM, Plautz EJ, Nudo RJ. A single injection of d-amphet-amine facilitates improvements in motor training following a focal cortical infarct in squirrel monkeys. Neurorehabil Neural Repair 2006. In press. [DOI] [PubMed]
  • 52.Adkins DL, Jones TA. D-amphetamine enhances skilled reaching after ischemic cortical lesions in rats. Neurosci Lett. 2005;380:214–218. doi: 10.1016/j.neulet.2005.01.036. [DOI] [PubMed] [Google Scholar]
  • 53.Gilmour G, Iversen SD, O’Neill MF, O’Neill MJ, Ward MA, Bannerman DM. Amphetamine promotes task-dependent recovery following focal cortical ischaemic lesions in the rat. Behav Brain Res. 2005;165:98–109. doi: 10.1016/j.bbr.2005.06.027. [DOI] [PubMed] [Google Scholar]
  • 54.Brown JA, Lutsep HL, Weinand M, Cramer SC. Motor cortex stimulation for the enhancement of recovery from stroke: A prospective, multicenter safety study. Neurosurgery. 2006;58:464–473. doi: 10.1227/01.NEU.0000204126.54417.46. [DOI] [PubMed] [Google Scholar]
  • 55.Plautz EJ, Barbay S, Frost SB, Friel KM, Dancause N, Zoubina EV, Stowe AM, Quaney BM, Nudo RJ. Post-infarct cortical plasticity and behavioral recovery using concurrent cortical stimulation and rehabilitative training: A feasibility study in primates. Neurol Res. 2003;25:801–810. doi: 10.1179/016164103771953880. [DOI] [PubMed] [Google Scholar]
  • 56.Adkins-Muir DL, Jones TA. Cortical electrical stimulation combined with rehabilitative training: Enhanced functional recovery and dendritic plasticity following focal cortical ischemia in rats. Neurol Res. 2003;25:780–788. doi: 10.1179/016164103771953853. [DOI] [PubMed] [Google Scholar]
  • 57.Kleim JA, Bruneau R, VandenBerg P, MacDonald E, Mulrooney R, Pocock D. Motor cortex stimulation enhances motor recovery and reduces peri-infarct dysfunction following ischemic insult. Neurol Res. 2003;25:789–793. doi: 10.1179/016164103771953862. [DOI] [PubMed] [Google Scholar]
  • 58.Carmichael ST, Archibeque I, Luke L, Nolan T, Momiy J, Li S. Growth-associated gene expression after stroke: Evidence for a growth-promoting region in peri-infarct cortex. Exp Neurol. 2005;193:291–311. doi: 10.1016/j.expneurol.2005.01.004. [DOI] [PubMed] [Google Scholar]
  • 59.Jones TA, Bury SD, Adkins-Muir DL, Luke LM, Allied RP, Sakata JT. Importance of behavioral manipulations and measures in rat models of brain damage and brain repair. ILAR J. 2003;44:144–152. doi: 10.1093/ilar.44.2.144. [DOI] [PubMed] [Google Scholar]

Articles from NeuroRx are provided here courtesy of Am. Soc. for Experimental NeuroTherapeutics

RESOURCES