title: Nogo Receptor 1 Confines a Disinhibitory Microcircuit to the Critical Period in Visual Cortex.
abstract: A characteristic of the developing mammalian visual system is a brief interval of plasticity, termed the "critical period," when the circuitry of primary visual cortex is most sensitive to perturbation of visual experience. Depriving one eye of vision (monocular deprivation [MD]) during the critical period alters ocular dominance (OD) by shifting the responsiveness of neurons in visual cortex to favor the nondeprived eye. A disinhibitory microcircuit involving parvalbumin-expressing (PV) interneurons initiates this OD plasticity. The gene encoding the neuronal nogo-66-receptor 1 (ngr1/rtn4r) is required to close the critical period. Here we combined mouse genetics, electrophysiology, and circuit mapping with laser-scanning photostimulation to investigate whether disinhibition is confined to the critical period by ngr1 We demonstrate that ngr1 mutant mice retain plasticity characteristic of the critical period as adults, and that ngr1 operates within PV interneurons to restrict the loss of intracortical excitatory synaptic input following MD in adult mice, and this disinhibition induces a "lower PV network configuration" in both critical-period wild-type mice and adult ngr1-/-mice. We propose that ngr1 limits disinhibition to close the critical period for OD plasticity and that a decrease in PV expression levels reports the diminished recent cumulative activity of these interneurons.
  
  
  
  Life experience refines brain circuits throughout development during specified critical periods. Abnormal experience during these critical periods can yield enduring maladaptive changes in neural circuits that impair brain function. In the developing visual system, visual deprivation early in life can result in amblyopia (lazy-eye), a prevalent childhood disorder comprising permanent deficits in spatial vision. Here we identify that the nogo-66 receptor 1 gene restricts an early and essential step in OD plasticity to the critical period. These findings link the emerging circuit-level description of OD plasticity to the genetic regulation of the critical period. Understanding how plasticity is confined to critical periods may provide clues how to better treat amblyopia.
authors: Developmental Neuroscience Program, Saban Research Institute, Children's Hospital Los Angeles, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California 90027, and.
authors: Céleste-Élise
authors: 0000-0001-9997-5745
authors: CÉ
authors: Stephany
authors: Department of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, California 92697.
authors: Taruna
authors: 0000-0003-3479-9378
authors: T
authors: Ikrar
authors: Department of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, California 92697.
authors: Collins
authors: C
authors: Nguyen
authors: Department of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, California 92697 xiangmix@uci.edu aaron.mcgee@louisville.edu.
authors: Xiangmin
authors: X
authors: Xu
authors: Developmental Neuroscience Program, Saban Research Institute, Children's Hospital Los Angeles, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California 90027, and xiangmix@uci.edu aaron.mcgee@louisville.edu.
authors: Aaron W
authors: 0000-0003-0843-4973
authors: AW
authors: McGee
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology; D000375:Aging / Q000378:metabolism; D000818:Animals; D003423:Critical Period, Psychological; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009415:Nerve Net / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D000070816:Nogo Receptor 1 / Q000235:genetics / Q000378:metabolism*; D014793:Visual Cortex / Q000502:physiology*; D014796:Visual Perception / Q000502:physiology*
chemical_list: D000070816:Nogo Receptor 1; C419790:Rtn4r protein, mouse
keywords: disinhibition; interneuron; ocular dominance; parvalbumin; plasticity