Glutamatergic Signaling in the Central Nervous System: Ionotropic and Metabotropic Receptors in Concert

Neuron. 2018 Jun 27;98(6):1080-1098. doi: 10.1016/j.neuron.2018.05.018.


Glutamate serves as both the mammalian brain's primary excitatory neurotransmitter and as a key neuromodulator to control synapse and circuit function over a wide range of spatial and temporal scales. This functional diversity is decoded by two receptor families: ionotropic glutamate receptors (iGluRs) and metabotropic glutamate receptors (mGluRs). The challenges posed by the complexity and physiological importance of each of these subtypes has limited our appreciation and understanding of how these receptors work in concert. In this review, by comparing both receptor families with a focus on their crosstalk, we argue for a more holistic understanding of neural glutamate signaling.

Keywords: G protein-coupled receptor; glutamate receptor; iGluR; ion channel; mGluR; neuromodulation; neurotransmitter; optogenetics; receptor crosstalk; synapse; synaptic plasticity.

Publication types

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

MeSH terms

  • Animals
  • Brain / metabolism*
  • Central Nervous System / metabolism
  • Glutamic Acid / metabolism*
  • Humans
  • Neuronal Plasticity
  • Neurotransmitter Agents / metabolism
  • Optogenetics
  • Receptors, Ionotropic Glutamate / metabolism*
  • Receptors, Ionotropic Glutamate / physiology
  • Receptors, Metabotropic Glutamate / metabolism*
  • Receptors, Metabotropic Glutamate / physiology
  • Synaptic Transmission


  • Neurotransmitter Agents
  • Receptors, Ionotropic Glutamate
  • Receptors, Metabotropic Glutamate
  • Glutamic Acid