Overview:

The metabotropic glutamate receptors (mGLURs) are key receptors in the modulation of excitatory synaptic transmission in the central nervous system. They are implicated in many forms of neural plasticity as well as learning and memory and drug abuse (1). Group I metabotropic glutamate receptors (consisting of mGLUR1 and mGLUR5) are G-protein-coupled neurotransmitter receptors that are localized in the perisynaptic region of the postsynaptic membrane. When activated, Group I mGLURs lead to stimulation of phospholipase and activation of Protein Kinase C. In contrast, activation of Group II metabotropic receptors (mGLUR2 and mGLUR3) leads to inhibition of adenylate cyclase. The mGLUR1 receptor may also be critically involved in limiting the deleterious effects of excitotoxicity (2). In contrast, the mGLUR5 receptor appears to be essential for late phase LTP in area CA1 of the hippocampus (3).

References:

1. Bhattacharya M, Babwah AV, et al, Ral and phospholipase D2-dependent pathway for constitutive metabotropic glutamate receptor endocytosis. J Neurosci 24:8752-8761. 2004.

2. Blaabjerg M, Fang LW, Zimmer J, Baskys A , Neuroprotection against NMDA excitotoxicity by group I metabotropic glutamate receptors is associated with reduction of NMDA stimulated currents. Exp Neurol 183:573-580. 2003.

3. Francesconi W, Cammalleri M, Sanna PP, The metabotropic glutamate receptor 5 is necessary for late-phase long-term potentiation in the hippocampal CA1 region. Brain Res 1022:12-18. 2004.

4. Wilson RI, Nicoll RA, Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses. Nature (London) 410:588-592. 2001.