Modulation of the main olfactory bulb circuitry by norepinephrine, dopamine and metabotropic glutamate receptors

Abstract

Several neuromodulatory transmitter systems, including norepinephrine (NE), dopamine (DA) and metabotropic glutamate receptor (mGluR) signaling systems, are present within the main olfactory bulb (MOB). There is very little information, however, about the physiological role of these modulatory transmitter systems in the MOB. The goal of the present studies, therefore, was to investigate the roles of NE, DA and mGluRs in the functioning of the MOB using electrophysiological approaches in vitro. Noradrenergic inputs to MOB arise from the nucleus locus coeruleus and terminate heavily in the granule cell layer, and to a lesser extent, in the mitral and external plexiform layers. We investigated the effects of noradrenergic receptor agents on the spontaneous and olfactory nerve (ON) evoked activity of mitral cells using extracellular, single unit recordings. NE, via activation of alpha1 noradrenergic receptors, increased mitral cell responses evoked by relatively weak, perithreshold stimulation of the ON. This suggests that NE release in the MOB may increase the sensitivity of mitral cells to weak odors. DA is present in the juxtaglomerular interneurons while DA D2 receptors are located on ON terminals. We investigated the role of DA in MOB synaptic processing using single unit and field potential recordings. DA and D2 receptor agonists suppressed the spontaneous and ON-evoked activity of mitral cells, and suppressed ON-evoked field excitatory postsynaptic potentials (fEPSPs) in the glomerular layer. DA effects on fEPSPs elicited by paired-pulse ON stimulation suggest that the actions of DA are mediated by D2 receptor-mediated inhibition of ON terminals. Anatomical studies suggest that mGluRs may play a role at several synapses in the MOB. ACPD-sensitive mGluRs are expressed by mitral/tufted (M/T) and granule cells. The goal of the final set of experiments was to investigate the role of ACPD-sensitive mGluRs in glutamatergic transmission from ON terminals to M/T cells and from M/T cells to granule cells. The results indicate that ACPD-sensitive mGluRs presynaptically increase glutamate release from M/T cell lateral dendrites, and postsynaptically depolarize granule cells. This suggests that activation of ACPD-sensitive mGluRs following glutamate release from M/T cells may increase activation of granule cells, and thus, facilitate lateral inhibition in the MOB.