Home LiteratureArticle Details
PMID: 18579732 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

In vivo calcium imaging reveals functional rewiring of single somatosensory neurons after stroke.

Winship IR, Murphy TH

Abstract

Functional mapping and microstimulation studies suggest that recovery after stroke damage can be attributed to surviving brain regions taking on the functional roles of lost tissues. Although this model is well supported by data, it is not clear how activity in single neurons is altered in relation to cortical functional maps. It is conceivable that individual surviving neurons could adopt new roles at the expense of their usual function. Alternatively, neurons that contribute to recovery may take on multiple functions and exhibit a wider repertoire of neuronal processing. In vivo two-photon calcium imaging was used in adult mice within reorganized forelimb and hindlimb somatosensory functional maps to determine how the response properties of individual neurons and glia were altered during recovery from ischemic damage over a period of 2-8 weeks. Single-cell calcium imaging revealed that the limb selectivity of individual neurons was altered during recovery from ischemia, such that neurons normally selective for a single contralateral limb processed information from multiple limbs. Altered limb selectivity was most prominent in border regions between stroke-altered forelimb and hindlimb macroscopic map representations, and peaked 1 month after the targeted insult. Two months after stroke, individual neurons near the center of reorganized functional areas became more selective for a preferred limb. These previously unreported forms of plasticity indicate that in adult animals, seemingly hardwired cortical neurons first adopt wider functional roles as they develop strategies to compensate for loss of specific sensory modalities after forms of brain damage such as stroke.

MeSH Terms
Adaptation, Physiological Afferent Pathways Animals Brain Ischemia/metabolism,physiopathology Brain Mapping Calcium Signaling Extremities/innervation Functional Laterality Male Mice Mice, Inbred C57BL Nerve Regeneration Neuronal Plasticity Neurons/metabolism,pathology Neurons, Afferent/metabolism,pathology Optics and Photonics Photic Stimulation Recovery of Function Somatosensory Cortex/pathology Staining and Labeling Stroke/metabolism,physiopathology
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Winship Ian R
Department of Psychiatry, Brain Research Centre, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3.
Murphy Timothy H
References (86)
86 references, click to expand
  1. Upregulation of GABAA-receptor alpha1- and alpha2-subunit mRNAs following ischemic cortical lesions in rats.
    Brain Res. 1999 Jan 16;816(1):234-7 PMID: 9878756
  2. Synchronous neuronal activity is a signal for axonal sprouting after cortical lesions in the adult.
    J Neurosci. 2002 Jul 15;22(14):6062-70 PMID: 12122067
  3. Astrocytic Ca2+ signaling evoked by sensory stimulation in vivo.
    Nat Neurosci. 2006 Jun;9(6):816-23 PMID: 16699507
  4. Induction of reproducible brain infarction by photochemically initiated thrombosis.
    Ann Neurol. 1985 May;17(5):497-504 PMID: 4004172
  5. Neural correlates of outcome after stroke: a cross-sectional fMRI study.
    Brain. 2003 Jun;126(Pt 6):1430-48 PMID: 12764063
  6. Neuroimaging experimental studies on brain plasticity in recovery from stroke.
    Eura Medicophys. 2007 Jun;43(2):241-54 PMID: 17589415
  7. Local networks in visual cortex and their influence on neuronal responses and dynamics.
    J Physiol Paris. 2004 Jul-Nov;98(4-6):429-41 PMID: 16274974
  8. Vicarious function within the human primary motor cortex? A longitudinal fMRI stroke study.
    Brain. 2005 May;128(Pt 5):1122-38 PMID: 15728652
  9. Functional recovery of forelimb response capacity after forelimb primary motor cortex damage in the rat is due to the reorganization of adjacent areas of cortex.
    Neuroscience. 1995 Oct;68(3):793-805 PMID: 8577374
  10. Behavioural report of single neuron stimulation in somatosensory cortex.
    Nature. 2008 Jan 3;451(7174):65-8 PMID: 18094684
  11. Plasticity of primary somatosensory cortex paralleling sensorimotor skill recovery from stroke in adult monkeys.
    J Neurophysiol. 1998 Apr;79(4):2119-48 PMID: 9535973
  12. Reorganization of neocortical representations after brain injury: a neurophysiological model of the bases of recovery from stroke.
    Prog Brain Res. 1987;71:249-66 PMID: 3588947
  13. Diverse modes of axon elaboration in the developing neocortex.
    PLoS Biol. 2005 Aug;3(8):e272 PMID: 16026180
  14. Imaging large-scale neural activity with cellular resolution in awake, mobile mice.
    Neuron. 2007 Oct 4;56(1):43-57 PMID: 17920014
  15. New patterns of intracortical projections after focal cortical stroke.
    Neurobiol Dis. 2001 Oct;8(5):910-22 PMID: 11592858
  16. Cloning of human GAP-43: growth association and ischemic resurgence.
    Neuron. 1988 Apr;1(2):133-9 PMID: 3272163
  17. Cortical functional architecture and local coupling between neuronal activity and the microcirculation revealed by in vivo high-resolution optical imaging of intrinsic signals.
    Proc Natl Acad Sci U S A. 1990 Aug;87(16):6082-6 PMID: 2117272
  18. Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo.
    Nat Methods. 2004 Oct;1(1):31-7 PMID: 15782150
  19. Stimulus-dependent changes in spike threshold enhance feature selectivity in rat barrel cortex neurons.
    J Neurosci. 2005 Mar 16;25(11):2983-91 PMID: 15772358
  20. Electrophysiological transcortical diaschisis after cortical photothrombosis in rat brain.
    Stroke. 1996 Jun;27(6):1105-9; discussion 1109-11 PMID: 8650722
  21. Electrophysiological changes in the surrounding brain tissue of photochemically induced cortical infarcts in the rat.
    Neurosci Lett. 1993 May 28;155(1):69-72 PMID: 8361665
  22. Extensive turnover of dendritic spines and vascular remodeling in cortical tissues recovering from stroke.
    J Neurosci. 2007 Apr 11;27(15):4101-9 PMID: 17428988
  23. Recovery recapitulates ontogeny.
    Trends Neurosci. 2000 Jun;23(6):265-71 PMID: 10838596
  24. Long-term cellular dysfunction after focal cerebral ischemia: in vitro analyses.
    Neuroscience. 1998 Jul;85(1):15-27 PMID: 9607699
  25. Dynamics of spontaneous activity in neocortical slices.
    Neuron. 2001 Dec 6;32(5):883-98 PMID: 11738033
  26. Functional recovery after brain lesion--contralateral neuromodulation: an fMRI study.
    Neuroreport. 2001 May 25;12(7):1543-7 PMID: 11388445
  27. Rapid astrocyte calcium signals correlate with neuronal activity and onset of the hemodynamic response in vivo.
    J Neurosci. 2007 Jun 6;27(23):6268-72 PMID: 17554000
  28. Plasticity of cortical projections after stroke.
    Neuroscientist. 2003 Feb;9(1):64-75 PMID: 12580341
  29. Rapid reversible changes in dendritic spine structure in vivo gated by the degree of ischemia.
    J Neurosci. 2005 Jun 1;25(22):5333-8 PMID: 15930381
  30. A comparison of different models of stroke on behaviour and brain morphology.
    Eur J Neurosci. 2003 Oct;18(7):1950-62 PMID: 14622227
  31. Spatial organization of neuronal population responses in layer 2/3 of rat barrel cortex.
    J Neurosci. 2007 Nov 28;27(48):13316-28 PMID: 18045926
  32. Effects of postlesion experience on behavioral recovery and neurophysiologic reorganization after cortical injury in primates.
    Neurorehabil Neural Repair. 2000;14(3):187-98 PMID: 11272475
  33. Neuronal damage and plasticity identified by microtubule-associated protein 2, growth-associated protein 43, and cyclin D1 immunoreactivity after focal cerebral ischemia in rats.
    Stroke. 1998 Sep;29(9):1972-80; discussion 1980-1 PMID: 9731626
  34. Reorganization of the human ipsilesional premotor cortex after stroke.
    Brain. 2004 Apr;127(Pt 4):747-58 PMID: 14749291
  35. Reorganization of movement representations in primary motor cortex following focal ischemic infarcts in adult squirrel monkeys.
    J Neurophysiol. 1996 May;75(5):2144-9 PMID: 8734610
  36. Imaging input and output of neocortical networks in vivo.
    Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):14063-8 PMID: 16157876
  37. Spatio-temporal subthreshold receptive fields in the vibrissa representation of rat primary somatosensory cortex.
    J Neurophysiol. 1998 Dec;80(6):2882-92 PMID: 9862892
  38. Functional magnetic resonance imaging of reorganization in rat brain after stroke.
    Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12766-71 PMID: 11606760
  39. Correlation between brain reorganization, ischemic damage, and neurologic status after transient focal cerebral ischemia in rats: a functional magnetic resonance imaging study.
    J Neurosci. 2003 Jan 15;23(2):510-7 PMID: 12533611
  40. Receptive field dynamics in adult primary visual cortex.
    Nature. 1992 Mar 12;356(6365):150-2 PMID: 1545866
  41. Synaptic integration by V1 neurons depends on location within the orientation map.
    Neuron. 2002 Dec 5;36(5):969-78 PMID: 12467599
  42. Axonal sprouting accompanies functional reorganization in adult cat striate cortex.
    Nature. 1994 Apr 21;368(6473):737-40 PMID: 8152484
  43. Response properties of vibrissa units in rat SI somatosensory neocortex.
    J Neurophysiol. 1978 May;41(3):798-820 PMID: 660231
  44. Highly ordered arrangement of single neurons in orientation pinwheels.
    Nature. 2006 Aug 24;442(7105):925-8 PMID: 16906137
  45. Coupling of total hemoglobin concentration, oxygenation, and neural activity in rat somatosensory cortex.
    Neuron. 2003 Jul 17;39(2):353-9 PMID: 12873390
  46. Spatiotemporal dynamics of cortical sensorimotor integration in behaving mice.
    Neuron. 2007 Dec 6;56(5):907-23 PMID: 18054865
  47. Collateral growth and angiogenesis around cortical stroke.
    Stroke. 2001 Sep;32(9):2179-84 PMID: 11546914
  48. Cellular and molecular mechanisms of neural repair after stroke: making waves.
    Ann Neurol. 2006 May;59(5):735-42 PMID: 16634041
  49. Fine mapping of the spatial relationship between acute ischemia and dendritic structure indicates selective vulnerability of layer V neuron dendritic tufts within single neurons in vivo.
    J Cereb Blood Flow Metab. 2007 Jun;27(6):1185-200 PMID: 17164811
  50. Middle cerebral artery (MCA) stroke produces dysfunction in adjacent motor cortex as detected by intracortical microstimulation in rats.
    Neuroscience. 2005;130(3):601-10 PMID: 15590144
  51. Sparse optical microstimulation in barrel cortex drives learned behaviour in freely moving mice.
    Nature. 2008 Jan 3;451(7174):61-4 PMID: 18094685
  52. Functional imaging with cellular resolution reveals precise micro-architecture in visual cortex.
    Nature. 2005 Feb 10;433(7026):597-603 PMID: 15660108
  53. Combined voltage and calcium epifluorescence imaging in vitro and in vivo reveals subthreshold and suprathreshold dynamics of mouse barrel cortex.
    J Neurophysiol. 2007 May;97(5):3751-62 PMID: 17360827
  54. Neural correlates of motor recovery after stroke: a longitudinal fMRI study.
    Brain. 2003 Nov;126(Pt 11):2476-96 PMID: 12937084
  55. Dynamic receptive fields of reconstructed pyramidal cells in layers 3 and 2 of rat somatosensory barrel cortex.
    J Physiol. 2003 Nov 15;553(Pt 1):243-65 PMID: 12949232
  56. Neocortical neural sprouting, synaptogenesis, and behavioral recovery after neocortical infarction in rats.
    Stroke. 1995 Nov;26(11):2135-44 PMID: 7482662
  57. Longitudinal changes in cerebral response to proprioceptive input in individual patients after stroke: an FMRI study.
    Neurorehabil Neural Repair. 2006 Sep;20(3):398-405 PMID: 16885426
  58. Reorganization of visual cortical maps after focal ischemic lesions.
    J Cereb Blood Flow Metab. 2003 Jul;23(7):811-20 PMID: 12843784
  59. Targeted bulk-loading of fluorescent indicators for two-photon brain imaging in vivo.
    Nat Protoc. 2006;1(1):380-6 PMID: 17406260
  60. In vivo two-photon calcium imaging of neuronal networks.
    Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):7319-24 PMID: 12777621
  61. Adult cortical dynamics.
    Physiol Rev. 1998 Apr;78(2):467-85 PMID: 9562036
  62. Motor cortex stimulation enhances motor recovery and reduces peri-infarct dysfunction following ischemic insult.
    Neurol Res. 2003 Dec;25(8):789-93 PMID: 14669520
  63. Induction of bilateral plasticity in sensory cortical maps by small unilateral cortical infarcts in rats.
    Eur J Neurosci. 2003 Feb;17(3):623-7 PMID: 12581180
  64. Functional architecture of cortex revealed by optical imaging of intrinsic signals.
    Nature. 1986 Nov 27-Dec 3;324(6095):361-4 PMID: 3785405
  65. Imaging the impact of cortical microcirculation on synaptic structure and sensory-evoked hemodynamic responses in vivo.
    PLoS Biol. 2007 May;5(5):e119 PMID: 17456007
  66. Homeostatic regulation of eye-specific responses in visual cortex during ocular dominance plasticity.
    Neuron. 2007 Jun 21;54(6):961-72 PMID: 17582335
  67. Intrinsic firing patterns and whisker-evoked synaptic responses of neurons in the rat barrel cortex.
    J Neurophysiol. 1999 Mar;81(3):1171-83 PMID: 10085344
  68. Functional reorganization of visual cortex maps after ischemic lesions is accompanied by changes in expression of cytoskeletal proteins and NMDA and GABA(A) receptor subunits.
    J Neurosci. 2004 Feb 25;24(8):1812-21 PMID: 14985421
  69. Two-photon imaging of cortical surface microvessels reveals a robust redistribution in blood flow after vascular occlusion.
    PLoS Biol. 2006 Feb;4(2):e22 PMID: 16379497
  70. The functional organization of the barrel cortex.
    Neuron. 2007 Oct 25;56(2):339-55 PMID: 17964250
  71. Foci of orientation plasticity in visual cortex.
    Nature. 2001 May 3;411(6833):80-6 PMID: 11333981
  72. Enriched rehabilitative training promotes improved forelimb motor function and enhanced dendritic growth after focal ischemic injury.
    J Neurosci. 2001 Jul 15;21(14):5272-80 PMID: 11438602
  73. The functional anatomy of motor recovery after stroke in humans: a study with positron emission tomography.
    Ann Neurol. 1991 Jan;29(1):63-71 PMID: 1996881
  74. Immunohistochemical evidence for dysregulation of the GABAergic system ipsilateral to photochemically induced cortical infarcts in rats.
    Neuroscience. 1998 Dec;87(4):871-9 PMID: 9759975
  75. Rapid morphologic plasticity of peri-infarct dendritic spines after focal ischemic stroke.
    Stroke. 2008 Apr;39(4):1286-91 PMID: 18323506
  76. Spatial-temporal distribution of whisker-evoked activity in rat somatosensory cortex and the coding of stimulus location.
    J Neurosci. 2000 Aug 15;20(16):6135-43 PMID: 10934263
  77. Bi-hemispheric contribution to functional motor recovery of the affected forelimb following focal ischemic brain injury in rats.
    Eur J Neurosci. 2005 Feb;21(4):989-99 PMID: 15787705
  78. Widespread and long-lasting alterations in GABA(A)-receptor subtypes after focal cortical infarcts in rats: mediation by NMDA-dependent processes.
    J Cereb Blood Flow Metab. 2002 Dec;22(12):1463-75 PMID: 12468891
  79. Adaptation-induced plasticity of orientation tuning in adult visual cortex.
    Neuron. 2000 Oct;28(1):287-98 PMID: 11087001
  80. Reorganization of remote cortical regions after ischemic brain injury: a potential substrate for stroke recovery.
    J Neurophysiol. 2003 Jun;89(6):3205-14 PMID: 12783955
  81. Synaptic plasticity during recovery from permanent occlusion of the middle cerebral artery.
    Neurobiol Dis. 2007 Jul;27(1):44-53 PMID: 17490888
  82. Background synaptic activity is sparse in neocortex.
    J Neurosci. 2006 Aug 9;26(32):8267-77 PMID: 16899721
  83. The functional microarchitecture of the mouse barrel cortex.
    PLoS Biol. 2007 Jul;5(7):e189 PMID: 17622195
  84. Neuronal hyperexcitability and reduction of GABAA-receptor expression in the surround of cerebral photothrombosis.
    J Cereb Blood Flow Metab. 1996 Sep;16(5):906-14 PMID: 8784234
  85. Afferent connections of the lateral agranular field of the rat motor cortex.
    J Comp Neurol. 1983 Jul 10;217(4):390-404 PMID: 6886060
  86. Extensive cortical rewiring after brain injury.
    J Neurosci. 2005 Nov 2;25(44):10167-79 PMID: 16267224
Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
2008-06-25
Pages
6592-606
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6670410
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com