ACTIVATION OF alpha 1 AND alpha 2 NORADRENERGIC RECEPTORS EXERT OPPOSING EFFECTS ON EXCITABILITY OF MAIN OLFACTORY BULB GRANULE CELLS

作者：Nai Q^*; Dong H W; Linster C; Ennis M

来源：Neuroscience, 2010, 169(2): 882-892.

DOI：10.1016/j.neuroscience.2010.05.010

• norepinephrine
• main olfactory bulb
• adrenergic receptor
• granule cells
• GABA

The mammalian main olfactory bulb (MOB) receives a dense noradrenergic innervation from the pontine nucleus locus coeruleus that is important for neonatal odor preference learning and odor processing in mature animals. Modulation of GABAergic granule cells (GCs) is thought to play a key role in the net functional impact of norepinephrine (NE) release in the MOB, yet there are few direct studies of the influence of NE on these cells. In the present study we investigated noradrenergic modulation of GC excitability using electrophysiological approaches in rat MOB slices. A moderate concentration of NE (10 mu M) and the alpha 1 receptor agonist phenylephrine (10 mu M) depolarized and increased spontaneous or current injection-evoked spiking in GCs. By contrast, low NE concentrations (0.1-1.0 mu M) or the alpha 2 receptor agonist clonidine (Clon, 10 mu M) hyperpolarized and decreased the discharge of GCs. The effects of NE (10 mu M) were blocked by antagonism of alpha 1 and alpha 2 receptors. Inhibitory effects of low NE concentrations were blocked or converted to excitatory responses by alpha 2 receptor blockade, whereas excitatory effects of the moderate NE concentration were converted to inhibitory responses after alpha 1 receptor blockade. NE (10 mu M) and phenylephrine elicited inward currents that reversed near the potassium equilibrium potential. The effects of NE and phenylephrine were associated with increased membrane input resistance. Clonidine elicited an outward current associated with decreased membrane input resistance that reversed near the potassium equilibrium potential. These results indicate that alpha 1 and alpha 2 receptor activation exert opposing effects on GC excitability. Low concentrations of NE acting via alpha 2 receptors suppress GC excitability, while higher concentrations of NE acting at alpha 1 receptors increase GC excitability. These findings are consistent with recent findings that alpha 1 and alpha 2 receptor activation increase and decrease, respectively, GABAergic inhibition of mitre! cells. The differential affinities of alpha 1 and alpha 2 noradrenergic receptor subtypes may allow for differential modulation of GABA release and olfactory processing as a function of the level of NE release, which in turn, is regulated by behavioral state.

• 出版日期2010-8-25