α_1A-Adrenergic regulation of inhibition in the olfactory bulb

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 GC→MC 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 α_1A-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 GABA_A 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 GC→MC inhibition in the OB results mostly from activation of the α_1A-AR subtype.