title: Experience with the "good" limb induces aberrant synaptic plasticity in the perilesion cortex after stroke.
abstract: Following unilateral stroke, the contralateral (paretic) body side is often severely impaired, and individuals naturally learn to rely more on the nonparetic body side, which involves learning new skills with it. Such compensatory hyper-reliance on the "good" body side, however, can limit functional improvements of the paretic side. In rats, motor skill training with the nonparetic forelimb (NPT) following a unilateral infarct lessens the efficacy of rehabilitative training, and reduces neuronal activation in perilesion motor cortex. However, the underlying mechanisms remain unclear. In the present study, we investigated how forelimb movement representations and synaptic restructuring in perilesion motor cortex respond to NPT and their relationship with behavioral outcomes. Forelimb representations were diminished as a result of NPT, as revealed with intracortical microstimulation mapping. Using transmission electron microscopy and stereological analyses, we found that densities of axodendritic synapses, especially axo-spinous synapses, as well as multiple synaptic boutons were increased in the perilesion cortex by NPT. The synaptic density was negatively correlated with the functional outcome of the paretic limb, as revealed in reaching performance. Furthermore, in animals with NPT, there was dissociation between astrocytic morphological features and axo-spinous synaptic density in perilesion motor cortex, compared with controls. These findings demonstrate that skill learning with the nonparetic limb following unilateral brain damage results in aberrant synaptogenesis, potentially of transcallosal projections, and this seems to hamper the functionality of the perilesion motor cortex and the paretic forelimb.
authors.affiliation: Department of Integrative Biology, University of California, Berkeley, Berkeley, California 94720, sooykim@berkeley.edu.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Psychology and.
authors.forename: Rachel P
authors.initials: RP
authors.lastname: Allred
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, and.
authors.forename: DeAnna L
authors.identifier: http://orcid.org/0000-0002-3063-5731
authors.initials: DL
authors.lastname: Adkins
authors.affiliation: Institute for Neuroscience, University of Texas at Austin, Austin, Texas 78712.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Tennant
authors.affiliation: Department of Psychology and.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Donlan
authors.affiliation: School of Biological and Health Systems Engineering, Arizona State University, Tempe, Arizona 85287.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Kleim
authors.affiliation: Department of Psychology and Institute for Neuroscience, University of Texas at Austin, Austin, Texas 78712.
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Jones
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000473:pathology / Q000648:ultrastructure; D001931:Brain Mapping; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000633:toxicity; D005081:Exercise Therapy; D005552:Forelimb / Q000503:physiopathology*; D007839:Functional Laterality / Q000502:physiology*; D008297:Male; D046529:Microscopy, Electron, Transmission; D009044:Motor Cortex / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure; D009048:Motor Skills / Q000502:physiology; D009068:Movement / Q000502:physiology; D053580:Muscle Strength; D009473:Neuronal Plasticity / Q000502:physiology*; D017729:Presynaptic Terminals / Q000473:pathology / Q000648:ultrastructure; D051381:Rats; D020318:Rats, Long-Evans; D020521:Stroke / Q000139:chemically induced / Q000473:pathology*; D000071939:Stroke Rehabilitation; D013569:Synapses / Q000473:pathology / Q000648:ultrastructure; D013997:Time Factors
chemical_list: D019332:Endothelin-1
keywords: astrocyte; forelimb behavior; learned nonuse; motor cortex; stroke recovery; synaptic plasticity