title: Neuregulin-1/ErbB4 Signaling Regulates Visual Cortical Plasticity.
abstract: Experience alters cortical networks through neural plasticity mechanisms. During a developmental critical period, the most dramatic consequence of occluding vision through one eye (monocular deprivation) is a rapid loss of excitatory synaptic inputs to parvalbumin-expressing (PV) inhibitory neurons in visual cortex. Subsequent cortical disinhibition by reduced PV cell activity allows for excitatory ocular dominance plasticity. However, the molecular mechanisms underlying critical period synaptic plasticity are unclear. Here we show that brief monocular deprivation during the critical period downregulates neuregulin-1(NRG1)/ErbB4 signaling in PV neurons, causing retraction of excitatory inputs to PV neurons. Exogenous NRG1 rapidly restores excitatory inputs onto deprived PV cells through downstream PKC-dependent activation and AMPA receptor exocytosis, thus enhancing PV neuronal inhibition to excitatory neurons. NRG1 treatment prevents the loss of deprived eye visual cortical responsiveness in vivo. Our findings reveal molecular, cellular, and circuit mechanisms of NRG1/ErbB4 in regulating the initiation of critical period visual cortical plasticity.
authors.affiliation: Department of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, Irvine, CA 92697-1275, USA.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, Irvine, CA 92697-1275, USA.
authors.forename: Taruna
authors.initials: T
authors.lastname: Ikrar
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697-4550, USA.
authors.forename: Melissa F
authors.initials: MF
authors.lastname: Davis
authors.affiliation: Department of Anesthesiology and Perioperative Care, University of California, Irvine, Irvine, CA 92697-4265, USA.
authors.forename: Nian
authors.initials: N
authors.lastname: Gong
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697-4550, USA.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Zheng
authors.affiliation: Department of Anesthesiology and Perioperative Care, University of California, Irvine, Irvine, CA 92697-4265, USA.
authors.forename: Z David
authors.initials: ZD
authors.lastname: Luo
authors.affiliation: Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA.
authors.forename: Cary
authors.initials: C
authors.lastname: Lai
authors.affiliation: Department of Neuroscience and Regenerative Medicine, Augusta University, Augusta, GA 30912, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Mei
authors.affiliation: Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, Irvine, CA 92697-4560, USA.
authors.forename: Todd C
authors.initials: TC
authors.lastname: Holmes
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA 92697-4550, USA.
authors.forename: Sunil P
authors.initials: SP
authors.lastname: Gandhi
authors.affiliation: Department of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, Irvine, CA 92697-1275, USA; Department of Biomedical Engineering, University of California, Irvine, Irvine, CA 92697-2715, USA; Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, CA 92697-2715, USA. Electronic address: xiangmin.xu@uci.edu.
authors.forename: Xiangmin
authors.initials: X
authors.lastname: Xu
mesh_terms: D000818:Animals; D003423:Critical Period, Psychological; D023882:Dominance, Ocular / Q000502:physiology*; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D008297:Male; D051379:Mice; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D020890:Neuregulin-1 / Q000494:pharmacology / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010320:Parvalbumins / Q000378:metabolism; D066247:Receptor, ErbB-4 / Q000502:physiology*; D012683:Sensory Deprivation / Q000502:physiology; D014793:Visual Cortex / Q000254:growth & development / Q000502:physiology*
chemical_list: D020890:Neuregulin-1; D010320:Parvalbumins; C587690:Erbb4 protein, mouse; D066247:Receptor, ErbB-4