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. Reiner and Levitz analyze the mechanisms of crosstalk between ionotropic and metabotropic glutamate receptor signaling, summarize its role in synaptic physiology and disease, and discuss novel approaches to develop a more holistic view of GluR biology.
Reiner, A., & Levitz, J. (2018, June 27). Glutamatergic Signaling in the Central Nervous System: Ionotropic and Metabotropic Receptors in Concert. Neuron. Cell Press. https://doi.org/10.1016/j.neuron.2018.05.018