Inhibitory circuit gating of auditory critical-period plasticity

Nat Neurosci. 2018 Feb;21(2):218-227. doi: 10.1038/s41593-017-0064-2. Epub 2018 Jan 22.


Cortical sensory maps are remodeled during early life to adapt to the surrounding environment. Both sensory and contextual signals are important for induction of this plasticity, but how these signals converge to sculpt developing thalamocortical circuits remains largely unknown. Here we show that layer 1 (L1) of primary auditory cortex (A1) is a key hub where neuromodulatory and topographically organized thalamic inputs meet to tune the cortical layers below. Inhibitory interneurons in L1 send narrowly descending projections to differentially modulate thalamic drive to pyramidal and parvalbumin-expressing (PV) cells in L4, creating brief windows of intracolumnar activation. Silencing of L1 (but not VIP-expressing) cells abolishes map plasticity during the tonotopic critical period. Developmental transitions in nicotinic acetylcholine receptor (nAChR) sensitivity in these cells caused by Lynx1 protein can be overridden to extend critical-period closure. Notably, thalamocortical maps in L1 are themselves stable, and serve as a scaffold for cortical plasticity throughout life.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Auditory Cortex / cytology
  • Auditory Cortex / physiology*
  • Bicuculline / pharmacology
  • Biguanides / pharmacology
  • Evoked Potentials, Auditory, Brain Stem / drug effects
  • Evoked Potentials, Auditory, Brain Stem / genetics
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / genetics
  • Female
  • Interneurons / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Nicotine / pharmacology
  • Nicotinic Agonists / pharmacology
  • Otoacoustic Emissions, Spontaneous / genetics
  • Parvalbumins / genetics
  • Parvalbumins / metabolism
  • Sensory Gating / genetics
  • Sensory Gating / physiology*
  • Serotonin Receptor Agonists / pharmacology
  • Vasoactive Intestinal Peptide / genetics
  • Vasoactive Intestinal Peptide / metabolism


  • Biguanides
  • Nicotinic Agonists
  • Parvalbumins
  • Serotonin Receptor Agonists
  • Vasoactive Intestinal Peptide
  • Nicotine
  • 1-(3-chlorophenyl)biguanide
  • Bicuculline