Activation of Group II Metabotropic Glutamate Receptors Suppresses Excitability of Mouse Main Olfactory Bulb External Tufted and Mitral Cells.

Hong-Wei Dong,Matthew Ennis

doi:10.3389/fncel.2017.00436

Hong-Wei Dong, Matthew Ennis

Open Access

https://doi.org/10.3389/fncel.2017.00436

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Abstract

Metabotropic glutamate receptors (mGluRs) are abundantly expressed in the rodent main olfactory bulb. The function of Group I mGluRs has been investigated in a number of studies, while the actions of Group II mGluRs, which include the mGluR2 and mGluR3 subtypes, have been less well explored. Here, we used electrophysiological approaches in mouse olfactory bulb slices to investigate how Group II mGluR activation and inactivation modifies the activity of external tufted (ET) and mitral cells. The Group II mGluR agonist DCG-IV was found to directly and uniformly reduce the spontaneous discharge of ET and mitral cells. The inhibitory effect of DCG-IV was absent in mitral cells with truncated apical dendrites, indicating a glomerular site of action. DCG-IV did not influence olfactory nerve-evoked monosynaptic responses in ET or mitral cells, indicating that Group II mGluRs do not presynaptically modulate glutamate release from olfactory nerve terminals. In contrast, DCG-IV suppressed polysynaptic responses in periglomerular cells evoked by olfactory nerve stimulation. DCG-IV also inhibited glutamate release from ET cells, and suppressed the spontaneous and olfactory nerve-evoked long-lasting depolarization in mitral cells. Applied alone, Group II receptor antagonists were without effect, suggesting that basal activation of these receptors is nil. These findings suggest that Group II mGluRs inhibit ET and mitral cell activity and further dampen intraglomerular excitatory circuits by suppressing glutamate release.

Highlights

Neurons in main olfactory bulb (MOB) express members of the three-metabotropic glutamate receptor family groups designated as: Group I, Group II and Group III (Conn and Pin, 1997)
In the presence of CNQX-APV-gabazine and LY341495 (2 μM), a selective Group II Metabotropic glutamate receptors (mGluRs) antagonist at low micromolar concentrations (Kingston et al, 1998), DCG-IV did not alter firing rate, burst rate or the number of spikes/burst (Figure 1C, D p > 0.05, n = 4, paired t-tests). These results show that activation of Group II mGluRs suppresses external tufted (ET) cell firing and this persists when ionotropic glutamate and GABA receptors are blocked (Figure 1D, p > 0.05 for all firing parameters, Kruskal-Willis Test followed by Chi-Square post-hoc tests)
The present results indicate that activation of Group II mGluRs directly inhibits ET and mitral cells, and reduces glutamate release from ET cells

Summary

Introduction

Neurons in main olfactory bulb (MOB) express members of the three-metabotropic glutamate receptor (mGluR) family groups designated as: Group I (mGluR1 and 5), Group II (mGluR2 and 3) and Group III (mGluR4 and 6-8) (Conn and Pin, 1997). The function of Group I mGluRs (mGluR1 and 5) in the MOB has been explored in a number of studies and has been linked to excitation of mitral/tufted and granule cells, slow oscillatory activity in response to olfactory nerve input and prolonged odor responses (Schoppa and Westbrook, 2001; Heinbockel et al, 2004, 2007; Yuan and Knopfel, 2006; Dong et al, 2007, 2009; Matsumoto et al, 2009). MGluR3 mRNA expression is negligible in the MOB, with only few scattered neurons of unknown identity observed (Ohishi et al, 1993). MGluR2 protein or mRNA localization studies report the presence of labeled neuron in all MOB layers, with substantial populations in the glomerular, mitral and granule cell. Studies using nonspecific mGluR2/3 antibodies (Petralia et al, 1996; Sahara et al, 2001) yielded results comparable to mGluR2 specific antibodies, suggesting that mGluR2 is the only Group II receptor with a significant functional role in the MOB

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