α1A-Adrenergic regulation of inhibition in the olfactory bulb
Article first published online: 19 FEB 2013
© 2013 The Authors. The Journal of Physiology © 2013 The Physiological Society
The Journal of Physiology
Volume 591, Issue 7, pages 1631–1643, April 2013
How to Cite
Zimnik, N. C., Treadway, T., Smith, R. S. and Araneda, R. C. (2013), α1A-Adrenergic regulation of inhibition in the olfactory bulb. The Journal of Physiology, 591: 1631–1643. doi: 10.1113/jphysiol.2012.248591
- Issue published online: 27 MAR 2013
- Article first published online: 19 FEB 2013
- Accepted manuscript online: 22 JAN 2013 08:05AM EST
- (Received 15 November 2012; accepted after revision 21 December 2012; first published online 24 December 2012)
- • Here, in mouse brain slices, we examined the cellular effects of noradrenaline to better understand its influence on olfactory bulb processing.
- • β- and α1-adrenergic receptor activation increases GABA currents in mitral cells in an age-dependent manner; the β-adrenergic effect is prominent only during early postnatal weeks, while the α1 effect is present at all ages.
- • This study focused on the α1-mediated increase in GABA inhibitory currents in mitral cells and found noradrenaline acts on the α1A-adrenergic receptor subtype to produce long-lasting excitation of granule cells.
- • The enhancement of inhibition by noradrenaline was consistent across a broad concentration range; at all concentrations, noradrenaline increased inhibitory currents in mitral cells.
- • Our studies highlight the important role of α1A-adrenergic receptor subtypes in increasing inhibition at dendrodendritic synapses, suggesting a synaptic mechanism for noradrenergic modulation of olfactory driven behaviours.
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 α1A-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.