Activation of α1 and α2 noradrenergic receptors exert opposing effects on excitability of main olfactory bulb granule cells

Abstract

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 µM) and the α1 receptor agonist phenylephrine (10 µM) depolarized and increased spontaneous or current injection-evoked spiking in GCs. By contrast, low NE concentrations (0.1–1.0 µM) or the α2 receptor agonist clonidine (10 µM) hyperpolarized and decreased the discharge of GCs. The effects of NE (10 µM) were blocked by antagonism of α1 and α2 receptors. Inhibitory effects of low NE concentrations were blocked or converted to excitatory responses by α2 receptor blockade, whereas excitatory effects of the moderate NE concentration were converted to inhibitory responses after α1 receptor blockade. NE (10 µM) 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 α1 and α2 receptor activation exert opposing effects on GC excitability. Low concentrations of NE acting via α2 receptors suppress GC excitability, while higher concentrations of NE acting at α1 receptors increase GC excitability. These findings are consistent with recent findings that α1 and α2 receptor activation increase and decrease, respectively, GABAergic inhibition of mitral cells. The differential affinities of α1 and α2 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.

Nonlinear effects of noradrenergic modulation of olfactory bulb function in adult rodents

“…Specifically, low concentrations of NE (0.1-1.0 M) or ␣2-receptor agonists hyperpolarized and inhibited granule cell spontaneous or evoked spike discharge (Nai et al 2010). By contrast, 10 M NE or ␣1-receptor agonists depolarized and increased granule cell discharge.…”

“…Modulatory inputs on mitral and granule cells can potentially affect the dynamics of neural activity as well as spike timing and degrees of synchronization. Levels of synchronization among bulbar outputs have been proposed to contribute to odor processing and learning experimentally (Beshel et al 2007;Brea et al 2009;Kay et al 2009;Nusser et al 2001). Modulatory inputs to granule and mitral cells can potentially regulate oscillatory dynamics of olfactory bulb processing and hence change the processing of odors, as proposed early on by Freeman and colleagues (Di Prisco and Freeman 1985;Gray et al 1986) and shown recently in slices of young rats by Schoppa and colleagues (Gire and Schoppa 2008;Pandipati et al 2010).…”

Action of the Noradrenergic System on Adult-Born Cells Is Required for Olfactory Learning in Mice

“…In a recent publication Nai et al (2010) reported that NA can either increases or decrease the excitability of adult granule cell depending on the applied concentration and the noradrenergic receptors subtype activated. Such effects were mediated by variation in the membrane resistance (R m ) through a modification of potassium conductance.…”

Olfactory bulb α2-adrenoceptor activation promotes rat pup odor-preference learning via a cAMP-independent mechanism

“…The evidence that clonidine reduces granule cell activity (Nai et al 2010;Pandipati et al 2010) predicts elevated mitral cell excitation during odor paired with clonidine. We performed pCREB immunohistochemistry as an index of mitral cell activation and to assess the role of CREB in the clonidine model.…”

“…Recently, studies of a 2 -adrenoceptor activation in the olfactory bulb in vitro have revealed receptor effects that could promote odor learning (Nai et al 2010;Pandipati et al 2010). In particular, the a 2 -adrenoceptor agonist, clonidine, has been shown to decrease granule cell excitability (Nai et al 2010), releasing the odor-encoding mitral cells from tonic inhibition, and to promote olfactory bulb synchrony at g EEG frequencies (Pandipati et al 2010).…”