Neuregulin-dependent regulation of fast-spiking interneuron excitability controls the timing of the critical period

Yu Gu, Trinh Tran, Sachiko Murase, Andrew Borrell, Alfredo Kirkwood, Elizabeth M. Quinlan

Research output: Contribution to journalArticle

Abstract

Maturation of excitatory drive onto fast-spiking interneurons (FS INs) in the visual cortex has been implicated in the control of the timing of the critical period for ocular dominance plasticity. However, the mechanisms that regulate the strength of these synapses over cortical development are not understood. Here we use a mouse model to show that neuregulin (NRG) and the receptor tyrosine kinase erbB4 regulate the timing of the critical period. NRG1 enhanced the strength of excitatory synapses onto FS INs, which inhibited ocular dominance plasticity during the critical period but rescued plasticity in transgenics with hypoexcitable FS INs. Blocking the effects of endogenous neuregulin via inhibition of erbBs rescued ocular dominance plasticity in postcritical period adults, allowing recovery from amblyopia induced by chronic monocular deprivation. Thus, the strength of excitation onto FS INs is a key determinant of critical period plasticity and is maintained at high levels by NRG-erbB4 signaling to constrain plasticity in adulthood.

Original languageEnglish (US)
Pages (from-to)10285-10295
Number of pages11
JournalJournal of Neuroscience
Volume36
Issue number40
DOIs
StatePublished - Oct 5 2016

Keywords

  • Critical period
  • Fast-spiking interneurons
  • Neuregulin
  • Ocular dominance plasticity
  • Parvalbumin

ASJC Scopus subject areas

  • Neuroscience(all)

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