Metabotropic glutamate receptors mGluR4 and mGluR8 regulate transmission in the lateral olfactory tract–piriform cortex synapse

The piriform cortex (PC) is the primary terminal zone of projections from the olfactory bulb, termed the lateral olfactory tract (LOT). The PC plays a critical role in processing of olfactory stimuli and is also a highly seizure prone area thought to be involved in some forms of temporal lobe epilepsy. Pharmacological and immunohistochemical studies provide evidence for the localization of various metabotropic glutamate receptors (GluRs) in the PC. We employed whole-cell patch clamp recordings from PC pyramidal cells to determine the roles of group III mGluRs in modulating synaptic transmission at the LOT–PC synapse. The group III mGluR agonist, l-AP4, induced a concentration-dependent inhibition of synaptic transmission at the LOT–PC synapse at concentrations that activate mGluR4 and mGluR8, but not mGluR7 or other mGluR subtypes (EC50 = 473 nM). In addition, the selective mGluR8 agonist, DCPG (300 nM), also suppressed synaptic transmission at the LOT synapse. Furthermore, the inhibitory actions of l-AP4 and Z-cyclopentyl-AP4, a selective mGluR4 agonist, were potentiated by the mGluR4 positive allosteric modulator, PHCCC (30 μM). The high potency of l-AP4, combined with the observed effects of DCPG and PHCCC, suggests that both mGluR4 and mGluR8 play a role in the l-AP4-induced inhibition of synaptic transmission at the LOT–PC synapse.