Chapter 13. Functional Crosstalk between Group I Metabotropic Glutamate Receptors and Ionotropic Glutamate Receptors Controls Synaptic Transmission

Abstract

The glutamatergic synapse harbours both ionotropic and metabotropic receptors that are tightly tethered by intracellular scaffolding proteins. We review how such a multiprotein scaffold supports functional interactions between the two receptor types. We provide evidence from the literature that glutamate metabotropic receptors can either potentiate or inhibit N-methyl-d-aspartate (NMDA) receptors. We also discuss recent data suggesting that these receptor interactions may support important physiological functions such as synaptic plasticity, learning and memory. For instance we describe previous work showing that metabotropic glutamate receptors can induce either long-term potentiation or depression of NMDA and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor synaptic responses in various regions of the brain and regulate synaptic strength by modulating NMDA receptor facilitation of endocannabinoid release. We report that dysfunctions of these regulations can contribute to mental retardation, drug addiction or neurodegenerative disorders such as Parkinson's and Alzheimer's diseases. Together, the data reported in this review highlight the importance of crosstalk between ionotropic and metabotropic glutamate receptors in synaptic functions and related physiological and pathological phenomena.