Excitatory synaptic dysfunction cell-autonomously decreases inhibitory inputs and disrupts structural and functional plasticity

Nat Commun. 2018 Jul 24;9(1):2893. doi: 10.1038/s41467-018-05125-4.


Functional circuit assembly is thought to require coordinated development of excitation and inhibition, but whether they are co-regulated cell-autonomously remains unclear. We investigate effects of decreased glutamatergic synaptic input on inhibitory synapses by expressing AMPAR subunit, GluA1 and GluA2, C-terminal peptides (GluA1CTP and GluA2CTP) in developing Xenopus tectal neurons. GluACTPs decrease excitatory synaptic inputs and cell-autonomously decreases inhibitory synaptic inputs in excitatory and inhibitory neurons. Visually evoked excitatory and inhibitory currents decrease proportionately, maintaining excitation/inhibition. GluACTPs affect dendrite structure and visual experience-dependent structural plasticity differently in excitatory and inhibitory neurons. Deficits in excitatory and inhibitory synaptic transmission and experience-dependent plasticity manifest in altered visual receptive field properties. Both visual avoidance behavior and learning-induced behavioral plasticity are impaired, suggesting that maintaining excitation/inhibition alone is insufficient to preserve circuit function. We demonstrate that excitatory synaptic dysfunction in individual neurons cell-autonomously decreases inhibitory inputs and disrupts neuronal and circuit plasticity, information processing and learning.

Publication types

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

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Animals, Genetically Modified
  • Dendrites / genetics
  • Dendrites / physiology
  • Excitatory Postsynaptic Potentials / physiology*
  • Larva / cytology
  • Larva / genetics
  • Larva / physiology
  • Microscopy, Confocal
  • Neural Inhibition / physiology*
  • Neuronal Plasticity / physiology*
  • Neurons / cytology
  • Neurons / metabolism
  • Neurons / physiology*
  • Peptides / genetics
  • Peptides / metabolism
  • Photic Stimulation
  • Receptors, AMPA / chemistry
  • Receptors, AMPA / genetics
  • Receptors, AMPA / metabolism
  • Superior Colliculi / cytology
  • Time-Lapse Imaging
  • Xenopus laevis


  • Peptides
  • Receptors, AMPA