Recurrent Dendrodendritic Inhibition of Accessory Olfactory Bulb Mitral Cells Requires Activation of Group I Metabotropic Glutamate Receptors

Abstract

Metabotropic glutamate receptors (mGluRs) modulate neural excitability and network tone in many brain regions. Expression of mGluRs is particularly high in the accessory olfactory bulb (AOB), a CNS structure critical for detecting chemicals that identify kin and conspecifics. Because of its relative simplicity and its direct projection to the hypothalamus, the AOB provides a model system for studying how mGluRs affect the flow of encoded sensory information to downstream areas. We investigated the role of group I mGluRs in synaptic processing in AOB slices and found that under control conditions, recurrent inhibition of principal neurons (mitral cells) was completely eliminated by the mGluR1 antagonist LY367385 [(S)-(ϩ)-␣-amino-4-carboxy-2 methylbenzeneacetic acid]. In addition, the group I mGluR agonist DHPG [(S)-3,5-dihydroxyphenylglycine; 20 M] induced a dramatic increase in the rate of spontaneous IPSCs. This increase was dependent on voltage-gated calcium channels but persisted even after blockade of ionotropic glutamatergic transmission and sodium channels. Together, these results indicate that mGluR1 plays a critical role in controlling information flow through the AOB and suggest that mGluR1 may be an important locus for experience-dependent changes in synaptic function.

Muscarinic receptor type 1 (M1) stimulation, probably through KCNQ/Kv7 channel closure, increases spontaneous GABA release at the dendrodendritic synapse in the mouse accessory olfactory bulb

“…Glutamatergic actions can be mediated by either ionotropic or metabotropic glutamate receptors. Among the metabotropic glutamate receptors, mGluR1 alone is responsible for increases in spontaneous GABA release from granule cells (Castro et al, 2007). Thus, we applied carbachol together in the presence of antagonists of ionotropic glutamate receptors (kynurenic acid, CNQX and D-AP5) and mGluR1 receptors (AP3 and MCPG).…”

“…Barium does enter through calcium channels, but compared with calcium, has negligible actions to release vesicles (Miledi, 1966). The marked effect of barium was also observed in the presence of a mixture of glutamatergic receptor inhibitors (5 mM kynurenic acid, 30 !M CNQX, 50 !M D-AP5, and 500 !M MCPG; n = 3), which should inhibit all of the glutamatergic receptors that are known to stimulate GABA release from granule cells (Castro et al, 2007). Furthermore, XE-991, a derivate of linodipine and a more potent and specific antagonist for the KCNQ channel (Elmedyb et al, 2007), increased the mIPSCs in the presence of the glutamatergic blockers (5 mM kynurenic acid, 30 !M CNQX, 50 !M D-AP5, and 500 !M MCPG in perfusate; from 10 to 50 !M XE-991, 7 out of 9 cells; Fig.…”

“…Glutamate is released from the mitral cell, while GABA is released from the granule cell (Jia et al, 1999;Taniguchi and Kaba, 2001). Spontaneous release of GABA from granule cells can be recorded as chloride currents in mitral cells using whole-cell recording; neuromodulators can increase the spontaneous mIPSC frequency via stimulation of noradrenergic !1 receptors (Araneda and Firestein, 2006) or mGluR1 metabotropic glutamate receptors (Castro et al, 2007).…”

α2-Adrenergic receptor activation promotes long-term potentiation at excitatory synapses in the mouse accessory olfactory bulb

“…Conventional whole-cell recordings with Cs + -internal solution in the pipette were performed in the presence of TTX (1 µM) to block Na + channels and thus prevent any contribution of axonal transmission. A depolarizing voltage step reported to evoke a relatively slow inward Ca 2+ current (Isaacson and Strowbridge 1998;Schoppa et al 1998;Taniguchi and Kaba 2001;Castro et al 2007) was followed by IPSCs (Fig. 5A).…”

“…Glutamate released from MC dendrites activates the GC dendrites, which in turn mediate the GABAergic dendrodendritic inhibition (DDI) of the MC dendrites (Jia et al 1999;Taniguchi and Kaba 2001). This feedback inhibition at the reciprocal synapses regulates MC output (Jia et al 1999;Taniguchi and Kaba 2001;Castro et al 2007;Taniguchi et al 2013).…”