Role of a metabotropic glutamate receptor in synaptic modulation in the accessory olfactory bulb

Abstract

Various functions of glutamate transmission are mediated by both ionotropic and metabotropic glutamate receptors. The metabotropic glutamate receptors (mGluRs) consists of at least six different subtypes that are classified into three subgroups, mGluR1/mGluR5, mGluR2/mGluR3, and mGluR4/mGluR6 (refs 1-5), but their physiological roles are largely unknown. Here we report the identification of a very potent agonist for mGluR2/mGluR3, DCG-IV, and the specific localization of mGluR2 in granule cell dendrites that form dendrodendritic synapses with mitral cells in the accessory olfactory bulb. Using the DCG-IV agonist for mGluR2 in combination with slice patch-recording, we demonstrate that the granule cell mGluR2 presynaptically suppresses inhibitory GABA (gamma-aminobutyrate) transmission to the mitral cell. Our results indicate that mGluR2 in granule cells plays an important role in the persistent excitation of olfactory sensory transmission in the accessory olfactory bulb by relieving mitral cells from the GABA inhibition.

Characterization of (2S,2′R,3′R)‐2‐(2′,3′‐[3H]‐Dicarboxycyclopropyl)glycine Binding in Rat Brain

“…DCG IV has been shown to inhibit forskolin-stimulated cyclic AMP formation with potencies of 300 and 200 nM for Chinese hamster ovary cells expressing mGlu2 and mGlu3 receptors, respectively (Hayashi et al, 1993), and these values fit well with the affinity found for both rat brain cortex and mGlu2-transfected membranes. DCG IV was also reported to inhibit NMDA receptors with an EC 50 close to 3 jiM (Hayashi et al, 1993). However, NMDA was unable to inhibit [ 3H] DCG IV binding, even at a high concentration.…”

“…It is interesting that the affinity constant determined by using the onesite model (180 nM) was extremely close to the value found for the mGlu2 receptor-transfected cell membranes~KD value of 160 nM (Cartmell et al, 1998)]. DCG IV has been shown to inhibit forskolin-stimulated cyclic AMP formation with potencies of 300 and 200 nM for Chinese hamster ovary cells expressing mGlu2 and mGlu3 receptors, respectively (Hayashi et al, 1993), and these values fit well with the affinity found for both rat brain cortex and mGlu2-transfected membranes. DCG IV was also reported to inhibit NMDA receptors with an EC 50 close to 3 jiM (Hayashi et al, 1993).…”

“…As DCG IV was shown to be inactive on both mGlul and mGlu4 receptors (Hayashi et al, 1993), the specificity of this ligand in rat brain homogenates is probably restricted to the group II mGlu receptors. This was also illustrated by the lack of effect of DHPG, the low potency of L-AP4 (ruling out a significant affinity to mGlu8 receptors), and the high potency of the new group II agonist and antagonist LY354740 and LY341495 (Monn et al, 1997;Schoepp et a!., 1997;Ornstein et al, 1998) …”

“…Group I (mGlu 1 and 5) receptors stimulate phosphatidylinositol hydrolysis when expressed in mammalian cells (Houamed et al, 1991;Masu et al, 1991;Abe et al, 1992) and are selectively activated by (S)-3,5-dihydroxyphenylglycine (DHPG) (Ito et al, 1992;Gereau and Conn, 1995). Group II (mGlu2 and 3) receptors are negatively coupled to cyclic AMP production when expressed in mammalian cells (Tanabe et al, 1992(Tanabe et al, , 1993 and are specifically activated by (+)-2-aminobicyclo [3.1 .0] hexane-2,6-dicarboxylate (LY354740) (Monn et al, 1997;Schoepp et al, 1997) and (2 S, 2' R, 3' R) -2-(2 ',3 '-dicarboxycyclopropyl) glycine (DCG IV), although this compound, at high concentration, appears to activate also N-methyl-D-aspartate (NMDA) receptors (Hayashi et al, 1993;Ishida et al, 1993). These receptors are also blocked by the highly potent, although not selective, new antagonist, 2-amino-2-(2-carboxycyclopropan-1-yl ) -3-(dibenzopyran-4-yl)propanoic acid (LY341495) (Chung et al, 1997;Ornstein et al, 1998).…”

General organization of the perinatal and adult accessory olfactory bulb in mice

“…Albeit during the last 2 decades, progress in the knowledge of the VNS in general and of the AOB in particular has been considerable (Hayashi et al, 1993;Taniguchi and Kaba, 2001;Araneda and Firestein, 2006), there are still some specific aspects of the AOB that require further exploration. Among the issues in need of precision is the exact morphology of the AOB, especially when it is obtained from mice.…”