TABLE 1

Summary of mGlu receptor subtype expression, signaling, and interacting partners

Group	Receptor	CNS Expression	Synaptic Localization	G protein Coupling	Primary Signaling Pathways	Interacting Partners
Group I	mGlu₁	Widespread in neurons	Predominantly postsynaptic	Primarily Gα_q/11 noncanocial Gα_i/0, Gα_s	PLCβ → IP3 + DAG hydrolysis phospholipase D MAPK/ERK mTOR/p70 S6 kinase	Activates NMDA receptors activates Ca²⁺ channels (e.g., Ca_v2.1) activates CaMKIIα
Group I	mGlu₅	Widespread in neurons	Predominantly postsynaptic	Primarily Gα_q/11 noncanocial Gα_i/0, Gα_s
Group II	mGlu₂	Widespread in neurons	Presynaptic and postsynaptic	Primarily Gα_i/0	Inhibition of adenylyl cyclase MAPK/ERK IP3-PI3 kinase	Activation of K⁺ channels inhibition of voltage-gated Ca²⁺ channels (e.g., N- type)
Group II	mGlu₃	Widespread in neurons, astrocytes	Presynaptic and postsynaptic	Primarily Gα_i/0	Inhibition of adenylyl cyclase MAPK/ERK IP3-PI3 kinase
Group III	mGlu₄	Widespread in neurons, high in cerebellum	Predominantly presynaptic	Primarily Gα_i/0 noncanocial Gα_q/1	Inhibition of adenylyl cylcase MAPK/ERK IP3 (mGlu7) stimulation of cGMP phosphodiesterase (mGlu6)	Activation of K⁺ channels inhibition of Ca²⁺ channels (P/Q subtype)
	mGlu₆	Retina, select neuron populations, microglia	Postsynaptic in retinal cells
	mGlu₇	Widespread in neurons	Active zone of presynaptic terminals
	mGlu₈	Lower and more restricted expression than mGlu4/7	Predominantly presynaptic

caMKII-alpha, Calcium/calmodulin-dependent kinase II; cGMP, cyclic guanosine monophosphate; DAG, diacyl-glycerol; G protein i/o alpha subunit; G protein Gs alpha subunit; G protein Gq alpha subunit; IP3, inositol 1,4,5-trisphosphate; MAPK/ERK, mitogen-activated protein kinase/extracellular receptor kinase; mTOR, mammalian target of rapamycin; PI3 kinase, phosphatidyl inositol 3-kinase; PLCβ, phospholipase Cβ; p70-S6 kinase, P70-S6; P/Q, P/Q-type calcium channel.