Modulation of lateral perforant path excitatory responses by metabotropic glutamate 8 (mGlu8) receptors

• Published in: Neuropharmacology Vol. 43; no. 2; pp. 223 - 230
• Main Authors: Zhai, Jin, Tian, Ming Ting, Wang, Yi, Yu, Jian Liang, Köster, Anja, Baez, Melvyn, Nisenbaum, Eric S.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Oxford Elsevier Ltd 01.08.2002; Elsevier
• Subjects: Animals; Autoreceptor; Biological and medical sciences; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Dentate gyrus; Dose-Response Relationship, Drug; Entorhinal cortex; Excitatory Postsynaptic Potentials - drug effects; Excitatory Postsynaptic Potentials - physiology; Female; Fundamental and applied biological sciences. Psychology; Hippocampus - drug effects; Hippocampus - physiology; In Vitro Techniques; Male; Metabotropic; mGluR; Mice; Mice, Inbred C57BL; Mice, Knockout; Perforant path; Perforant Pathway - drug effects; Perforant Pathway - physiology; Receptors, Metabotropic Glutamate - agonists; Receptors, Metabotropic Glutamate - deficiency; Receptors, Metabotropic Glutamate - genetics; Vertebrates: nervous system and sense organs; Autoreceptor; Metabotropic; Dentate gyrus; Entorhinal cortex; mGluR; Perforant path; Rodentia; Central nervous system; Electrophysiology; In vitro; Vertebrata; Synapse; Mammalia; mglu8 glutamate receptor; Metabotropic receptor; Mouse; Animal; Perforant pathway; Mechanism of action; Excitatory postsynaptic potential; Hippocampus; Brain (vertebrata)
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/S0028-3908(02)00087-4

The contribution of metabotropic glutamate 8 (mGlu8) receptors to modulation of medial and lateral perforant path (MPP and LPP) inputs to the dentate gyrus was investigated using electrophysiological recording of field excitatory postsynaptic potentials (fEPSPs) from hippocampal slices taken from wild-type and mGlu8 receptor knockout animals. Application of the selective group III mGlu receptor agonist, L-AP4 (1–100 μM), reduced fEPSPs evoked by LPP, but not MPP stimulation in wild-type slices in a concentration-dependent manner (EC 50=4.7 μM). The selective mGlu8 receptor agonist, DCPG (1–30 μM) also suppressed LPP fEPSPs with an EC 50 value of 3.1 μM. The L-AP4-induced reduction in LPP fEPSPs could be blocked by the group III antagonist, MSOP (100 μM) in wild-type slices and was eliminated in mGlu8 receptor-deficient slices. Additional experiments showed that MPP fEPSPs were suppressed by the group II agonist, LY379268 (0.01–3 μM) in control slices (EC 50=153.1 nM); an effect that was not altered in mGlu8 receptor knockout slices (EC 50=153.8 nM) . In addition, LY379268 had little effect on fEPSPs evoked by LPP stimulation in mGlu8 receptor-deficient slices. In conjunction with recent receptor localization studies, these results suggest that the mGlu8 receptors serve as autoreceptors on LPP afferents to the dentate gyrus.