Group 5 metabotropic glutamate receptors: role in modulating cortical activity and relevance to cognition.
Group 5 metabotropic glutamate (mGlu(5)) 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 mGlu(5) 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 mGlu(5) 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 mGlu(5) receptor potentiators.
Homayoun
Houman
H
Department of Neuroscience, University of Pittsburgh, A210 Langley Hall, Pittsburgh, PA 15260, USA. homayounh@upmc.edu
Moghaddam
Bita
B
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D017397:Prefrontal Cortex / Q000378:metabolism / Q000502:physiology*; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000145:classification / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism
D014150:Antipsychotic Agents; D018691:Excitatory Amino Acid Antagonists; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate