Group 5 metabotropic glutamate receptors: Role in modulating cortical activity and relevance to cognition

Group 5 metabotropic glutamate (mGlu₅) receptors are abundant in forebrain and limbic regions and provide a novel pharmacological target for modulation of cognition. Here, we review recent advances in understanding the electrophysiology of these receptors which reveal a role for mGlu₅ receptors in the regulation of tonic and bursting modes of neuronal firing, maintenance of distinct forms of synaptic plasticity, and reversal of detrimental effects of NMDA receptor antagonism on cortical neuronal activity. Furthermore, recordings using recently developed positive allosteric modulators of the mGlu₅ receptor suggest that these agents have an electrophysiological profile comparable to the antipsychotic agent clozapine. These findings, in conjunction with behavioral evidence from preclinical studies of cognition, suggest a potential precognitive profile for the mGlu₅ receptor potentiators.