Delayed maturation of fast-spiking interneurons is rectified by activation of the TrkB receptor in the mouse model of fragile X syndrome

Toshihiro Nomura, Timothy F. Musial, John J. Marshall, Yiwen Zhu, Christine L. Remmers, Jian Xu, Daniel A. Nicholson, Anis Contractor*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Fragile X syndrome (FXS) is a neurodevelopmental disorder that is a leading cause of inherited intellectual disability, and the most common known cause of autism spectrum disorder. FXS is broadly characterized by sensory hypersensitivity and several developmental alterations in synaptic and circuit function have been uncovered in the sensory cortex of the mouse model of FXS (Fmr1 KO). GABAmediated neurotransmission and fast-spiking (FS) GABAergic interneurons are central to cortical circuit development in the neonate. Here we demonstrate that there is a delay in the maturation of the intrinsic properties of FS interneurons in the sensory cortex, and a deficit in the formation of excitatory synaptic inputs on to these neurons in neonatal Fmr1 KO mice. Both these delays in neuronal and synaptic maturation were rectified by chronic administration of a TrkB receptor agonist. These results demonstrate that the maturation of the GABAergic circuit in the sensory cortex is altered during a critical developmental period due in part to a perturbation in BDNF-TrkB signaling, and could contribute to the alterations in cortical development underlying the sensory pathophysiology of FXS.

Original languageEnglish (US)
Pages (from-to)11298-11310
Number of pages13
JournalJournal of Neuroscience
Volume37
Issue number47
DOIs
StatePublished - Nov 22 2017

Keywords

  • Critical period
  • Fast-spiking interneuron
  • Fragile X syndrome
  • Somatosensory cortex
  • Synapse
  • TrkB

ASJC Scopus subject areas

  • Neuroscience(all)

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