Glutamate plays a dominant role in neurotransmission at number of synapses in the mammalian main olfactory bulb (MOB). Work from our laboratory as well as by others over the last 5 years has demonstrated that (1) sensory transmission from olfactory nerve (ON) terminals to mitral/tufted cells (M/TCs) and juxtaglomerular cells, and (2) transmission from MiTCs to granule cells (GCs), is mediated by glutamate acting at AMPA and NMDA receptors. Additionally, glutamate released by M!TCs can activate AMPA and NMDA receptors on other MrrCs, providing a source of autoexcitation that enhances responses to ON input. Receptor localization studies suggest that another class of glutamate receptors, metabotropic glutamate receptors (mGluRs), are densely expressed at several glutamatergic synapses in the MOB. In paiticular, the density of mGluRs on MTFCs and GCs are higher than most other regions of the brain. However, the role(s) of mGluRs in synaptic processing in the MOB are unknown. The goal of the present proposal is to close this gap. Preliminary data show that the operation of the MOB network, and the excitability of MCs and GCs, are potently modulated by activation and inactivation of mGluRs. Direct activation of mGluRs on MCs increases their excitability, and in turn, increases their excitatory drive on GCs. Activation of mGluRs also directly increases GC excitability and GABA release. Inactivation of mGluRs, by contrast, potently attenuates MC - GC excitatory transmission. Based on these results and other preliminary data, we hypothesize that activation of mGluRs by synaptically-released glutamate positively modulates lateral inhibition and increases contrast in the MOB network. In agreement with this hypothesis, preliminary studies using optical imaging of voltage-sensitive dyes show that mGluR antagonists dramatically decrease the amplitude, spatial spread and duration of postsynaptic activity in the external plexiform layer evoked by focal glomerular stimulation. This suggests that endogenous activation of mGluRs amplifies lateral inhibition. This hypothesis will be tested at the cellular and circuit levels using patch clamp electrophysiology and functional imaging approaches in mammalian MOB slices from rats, as well as slices from mice with targeted gene deletions of the major mGluRs expressed by MCs and GCs. The overarching goal of this proposal is to elucidate the roles of mGluRs in the operation of the MOB network and odor coding.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
Project #
Application #
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Davis, Barry
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Tennessee Health Science Center
Anatomy/Cell Biology
Schools of Medicine
United States
Zip Code
Dong, Hong-Wei; Ennis, Matthew (2014) Activation of group I metabotropic glutamate receptors enhances persistent sodium current and rhythmic bursting in main olfactory bulb external tufted cells. J Neurophysiol 111:641-7
Dong, Hong-Wei; Davis, James C; Ding, ShengYuan et al. (2012) Expression of transient receptor potential (TRP) channel mRNAs in the mouse olfactory bulb. Neurosci Lett 524:49-54
Nai, Q; Dong, H W; Linster, C et al. (2010) Activation of alpha1 and alpha2 noradrenergic receptors exert opposing effects on excitability of main olfactory bulb granule cells. Neuroscience 169:882-92
Nai, Qiang; Dong, Hong-Wei; Hayar, Abdallah et al. (2009) Noradrenergic regulation of GABAergic inhibition of main olfactory bulb mitral cells varies as a function of concentration and receptor subtype. J Neurophysiol 101:2472-84
Dong, Hong-Wei; Heinbockel, Thomas; Hamilton, Kathryn A et al. (2009) Metabotropic glutamate receptors and dendrodendritic synapses in the main olfactory bulb. Ann N Y Acad Sci 1170:224-38
Dong, Hong-Wei; Hayar, Abdallah; Callaway, Joseph et al. (2009) Group I mGluR activation enhances Ca(2+)-dependent nonselective cation currents and rhythmic bursting in main olfactory bulb external tufted cells. J Neurosci 29:11943-53
Heinbockel, Thomas; Laaris, Nora; Ennis, Matthew (2007) Metabotropic glutamate receptors in the main olfactory bulb drive granule cell-mediated inhibition. J Neurophysiol 97:858-70
Laaris, Nora; Puche, Adam; Ennis, Matthew (2007) Complementary postsynaptic activity patterns elicited in olfactory bulb by stimulation of mitral/tufted and centrifugal fiber inputs to granule cells. J Neurophysiol 97:296-306
Dong, Hong-Wei; Hayar, Abdallah; Ennis, Matthew (2007) Activation of group I metabotropic glutamate receptors on main olfactory bulb granule cells and periglomerular cells enhances synaptic inhibition of mitral cells. J Neurosci 27:5654-63
Heinbockel, Thomas; Hamilton, Kathryn A; Ennis, Matthew (2007) Group I metabotropic glutamate receptors are differentially expressed by two populations of olfactory bulb granule cells. J Neurophysiol 97:3136-41

Showing the most recent 10 out of 25 publications