Input-Specific Metaplasticity in the Visual Cortex Requires Homer1a-Mediated mGluR5 Signaling

Neuron. 2019 Nov 20;104(4):736-748.e6. doi: 10.1016/j.neuron.2019.08.017. Epub 2019 Sep 25.

Abstract

Effective sensory processing depends on sensory experience-dependent metaplasticity, which allows homeostatic maintenance of neural network activity and preserves feature selectivity. Following a strong increase in sensory drive, plasticity mechanisms that decrease the strength of excitatory synapses are preferentially engaged to maintain stability in neural networks. Such adaptation has been demonstrated in various model systems, including mouse primary visual cortex (V1), where excitatory synapses on layer 2/3 (L2/3) neurons undergo rapid reduction in strength when visually deprived mice are reexposed to light. Here, we report that this form of plasticity is specific to intracortical inputs to V1 L2/3 neurons and depends on the activity of NMDA receptors (NMDARs) and group I metabotropic glutamate receptor 5 (mGluR5). Furthermore, we found that expression of the immediate early gene (IEG) Homer1a (H1a) and its subsequent interaction with mGluR5s are necessary for this input-specific metaplasticity.

Keywords: H1a; NMDA receptor; mGluR5; metabotropic glutamate receptor; metaplasticity; visual cortex.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Female
  • Homeostasis / physiology
  • Homer Scaffolding Proteins / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neuronal Plasticity / physiology*
  • Receptor, Metabotropic Glutamate 5 / metabolism*
  • Signal Transduction / physiology*
  • Visual Cortex / metabolism*

Substances

  • Grm5 protein, mouse
  • Homer Scaffolding Proteins
  • Homer1 protein, mouse
  • Receptor, Metabotropic Glutamate 5