title: Blocking PirB up-regulates spines and functional synapses to unlock visual cortical plasticity and facilitate recovery from amblyopia.
abstract: During critical periods of development, the brain easily changes in response to environmental stimuli, but this neural plasticity declines by adulthood. By acutely disrupting paired immunoglobulin-like receptor B (PirB) function at specific ages, we show that PirB actively represses neural plasticity throughout life. We disrupted PirB function either by genetically introducing a conditional PirB allele into mice or by minipump infusion of a soluble PirB ectodomain (sPirB) into mouse visual cortex. We found that neural plasticity, as measured by depriving mice of vision in one eye and testing ocular dominance, was enhanced by this treatment both during the critical period and when PirB function was disrupted in adulthood. Acute blockade of PirB triggered the formation of new functional synapses, as indicated by increases in miniature excitatory postsynaptic current (mEPSC) frequency and spine density on dendrites of layer 5 pyramidal neurons. In addition, recovery from amblyopia--the decline in visual acuity and spine density resulting from long-term monocular deprivation--was possible after a 1-week infusion of sPirB after the deprivation period. Thus, neural plasticity in adult visual cortex is actively repressed and can be enhanced by blocking PirB function.
authors.affiliation: Department of Biology and Bio-X, James H. Clark Center, Stanford University, Stanford, CA 94305, USA.
authors.forename: David N
authors.initials: DN
authors.lastname: Bochner
authors.affiliation: Department of Biology and Bio-X, James H. Clark Center, Stanford University, Stanford, CA 94305, USA.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Sapp
authors.affiliation: Department of Biology and Bio-X, James H. Clark Center, Stanford University, Stanford, CA 94305, USA.
authors.forename: Jaimie D
authors.initials: JD
authors.lastname: Adelson
authors.affiliation: Division of Neurobiology, Department of Molecular and Cell Biology and Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Siyu
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Biology and Bio-X, James H. Clark Center, Stanford University, Stanford, CA 94305, USA.
authors.forename: Hanmi
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Biology and Bio-X, James H. Clark Center, Stanford University, Stanford, CA 94305, USA.
authors.forename: Maja
authors.initials: M
authors.lastname: Djurisic
authors.affiliation: Vertex Pharmaceuticals Inc., Cambridge, MA 02139, USA.
authors.forename: Josh
authors.initials: J
authors.lastname: Syken
authors.affiliation: Division of Neurobiology, Department of Molecular and Cell Biology and Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Dan
authors.affiliation: Department of Biology and Bio-X, James H. Clark Center, Stanford University, Stanford, CA 94305, USA. cshatz@stanford.edu.
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Shatz
mesh_terms: D000550:Amblyopia / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D000831:Animals, Newborn; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism*; D023882:Dominance, Ocular / Q000187:drug effects; D017353:Gene Deletion; D005838:Genotype; D019426:Integrases / Q000378:metabolism; D008024:Ligands; D051379:Mice; D009473:Neuronal Plasticity / Q000187:drug effects; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D020127:Recovery of Function / Q000187:drug effects; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D014792:Visual Acuity / Q000187:drug effects; D014793:Visual Cortex / Q000187:drug effects / Q000503:physiopathology*
chemical_list: D008024:Ligands; C105949:Pirb protein, mouse; D011971:Receptors, Immunologic; D013629:Tamoxifen; C045073:Cre recombinase; D019426:Integrases