title: α(1A)-Adrenergic regulation of inhibition in the olfactory bulb.
abstract: By regulating inhibition at dendrodendritic synapses between mitral and granule cells (GCs), noradrenergic neurons extending from the brainstem provide an input essential for odour processing in the olfactory bulb (OB). In the accessory OB (AOB), we have recently shown that noradrenaline (NA) increases GABA inhibitory input on to mitral cells (MCs) by exciting GCs. Here, we show that GCs in the main OB (MOB) exhibit a similar response to NA, indicating a common mechanism for noradrenergic regulation of GCMC inhibition throughout the OB. In GCs of the MOB, NA (10 μM) produced a robust excitatory effect that included a slow afterdepolarization that followed a train of action potentials evoked by a current stimulus. The depolarization and slow afterdepolarization in GCs were blocked by the α1A-adrenergic receptor (AR) selective antagonist WB 4101 (30 nm) and mimicked by the α(1A)-AR selective agonist A 61603 (1 μM). In recordings from MCs, A 61603 (30 nm-1 μM) produced a sizeable increase in the frequency of spontaneous and miniature IPSCs, an effect completely abolished by the GABAA receptor antagonist gabazine (5 μM). Likewise, activation of β-ARs increased the frequency of spontaneous IPSCs; however, this effect was smaller and confined to the first postnatal weeks. NA enhanced inhibition in MCs across a broad concentration range (0.1-30 μM) and its effects were completely abolished by a mixture of α1- and β-AR antagonists (1 μM prazosin and 10 μM propranolol). Furthermore, the general α2-AR agonist clonidine (10 μM) failed to affect sIPSC frequency. Thus, the NA-mediated increase in GCMC inhibition in the OB results mostly from activation of the α1A-AR subtype.
authors.affiliation: Department of Biology, University of Maryland, College Park, MD 20742, USA.
authors.forename: Nathan C
authors.initials: NC
authors.lastname: Zimnik
authors.forename: Tyler
authors.initials: T
authors.lastname: Treadway
authors.forename: Richard S
authors.initials: RS
authors.lastname: Smith
authors.forename: Ricardo C
authors.initials: RC
authors.lastname: Araneda
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D009830:Olfactory Bulb / Q000502:physiology*; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D013569:Synapses / Q000502:physiology
chemical_list: D000316:Adrenergic alpha-Agonists; D018340:Receptors, Adrenergic, alpha-1; D009638:Norepinephrine