Modulation of lateral perforant path excitatory responses by metabotropic glutamate 8 (mGlu8) receptors.
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 microM), reduced fEPSPs evoked by LPP, but not MPP stimulation in wild-type slices in a concentration-dependent manner (EC(50) = 4.7 microM). The selective mGlu8 receptor agonist, DCPG (1-30 microM) also suppressed LPP fEPSPs with an EC(50) value of 3.1 microM. The L-AP4-induced reduction in LPP fEPSPs could be blocked by the group III antagonist, MSOP (100 microM) 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 microM) 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.
Zhai
Jin
J
Neuroscience Division, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
Tian
Ming Ting
MT
Wang
Yi
Y
Yu
Jian Liang
JL
Köster
Anja
A
Baez
Melvyn
M
Nisenbaum
Eric S
ES
D000818:Animals; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019580:Perforant Pathway / Q000187:drug effects / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000172:deficiency* / Q000235:genetics
D018094:Receptors, Metabotropic Glutamate; C111435:metabotropic glutamate receptor 8