Adrenergic modulation of olfactory bulb circuitry affects odor discrimination

Abstract

A rodent's survival depends upon its ability to perceive odor cues necessary to guide mate selection, sexual behavior, foraging, territorial formation, and predator avoidance. Arguably, the need to discriminate odor cues in a complex olfactory environment requires a highly adaptable olfactory system. Indeed, it has been proposed that context-dependent modulation of the initial sensory relay could alter olfactory perception. Interestingly, 40% of the adrenergic innervation from the locus coeruleus, fibers that are activated by contextual cues, innervates the first relay station in the olfactory system (the main olfactory bulb). Here we utilize restricted pharmacological inhibition of olfactory bulb noradrenergic receptors in awake-behaving animals. We show that combined blockade of ␣ and ␤ adrenergic receptors does not impair two-odor discrimination behavior per se but does impair the ability to discriminate perceptually similar odors. Thus, contextual cues conveyed by noradrenergic fibers alter processing before the second synapse in the olfactory cortex, resulting in tuning of the ability to discriminate between similar odors.Particularly intriguing, but poorly understood, is the potential role of adrenergic modulation of the main olfactory bulb (MOB) in adults. The MOB receives strong innervation from the locus coeruleus (LC)-noradrenaline (NA) system, and in rodents ∼40% of LC fibers target the MOB. The fibers are known to be densest in the internal plexiform and granule cell layers, less dense in the external plexiform layer, and sparse in the glomerular layer (McLean et al. 1989) (Fig. 1). Both ␣ and ␤ adrenergic receptors are expressed by cells in the MOB (Pieribone et al. 1994;Woo and Leon 1995;Day et al. 1997). Current evidence suggests that the LC-NA system has a behaviorally meaningful role within the MOB of adult animals engaged in olfactory learning tasks. There is a modest but reproducible release of NA in the MOB during operant conditioning in adult mice (Brennan et al. 1998). In addition, detection of the rewarded odor, presumably relayed from the prefrontal cortex to LC, triggers a brief phasic increase in firing of LC neurons (Bouret and Sara 2004). Gray and coworkers also find that the topical application of propranolol, a ␤ adrenergic antagonist, to the MOB abolished changes in ␥ frequency (40-100 Hz) oscillations in the local field potential elicited by the rewarded odor in an odor discrimination task (Gray et al. 1986). The modulation of odor-induced local field potential oscillations has been postulated to play a role in olfactory learning (Martin et al. 2006). Surprisingly, although the adrenergic effect on odor-induced changes in local field potential oscillations found by Gray and coworkers was robust, propranolol did not change the ability of rabbits to discriminate between odors. Data presented in this paper provide an explanation for the paradoxical observation of Gray and coworkers, as we show that blockade of both ␣ and ␤ adrenergic receptors in the MOB is necessary to attain a chan...

Distinct Roles of Bulbar Muscarinic and Nicotinic Receptors in Olfactory Discrimination Learning

“…In the intact bulbar circuit, there are numerous cellular mechanisms that govern the dynamics of granule cells (Trombley and Shepherd, 1992;Halabisky et al, 2000;Pressler and Strowbridge, 2006;Balu et al, 2007;Pressler et al, 2007;Nai et al, 2010). Our behavioral results complement a growing number of studies suggesting that manipulations that alter fast oscillatory activity in the OB, presumably by altering the granule cell network, impair odor discrimination learning (Stopfer et al, 1997;Doucette et al, 2007;Mandairon et al, 2008;Lepousez and Lledo, 2013). In general, results from these studies indicate that olfactory discrimination learning is impaired when synchrony among OB outputs is disrupted.…”

“…Interestingly, this discrepancy in the role of bulbar cholinergic receptors across behavioral paradigms parallels observations made following blockade of bulbar noradrenergic (NA) receptors. To be specific, Mandairon et al (2008) found only a modest impairment in learning in a digging-based paradigm following blockade of bulbar NA receptors, whereas Doucette et al (2007) observed complete abolishment of learning in a Go/No-Go operant paradigm when blocking bulbar NA receptors. It is possible that the discrepancy between behavioral paradigms arises from differences in the duration of odor exposure on each trial-animals performing a digging-based task may be exposed to the odor for much longer, facilitating rapid learning.…”

“…In particular, disruption of normal OB dynamics by local application of antagonists to cholinergic (Mandairon et al, 2006b;Chaudhury et al, 2009), noradrenergic (Doucette et al, 2007;Mandairon et al, 2008), or GABAergic receptors (Stopfer et al, 1997;Lepousez and Lledo, 2013) impairs the discrimination of similar odorants while sparing discrimination of dissimilar odorants. Based on these previous results, we hypothesized that the variability in performance across odor sets, especially in rats infused with MLA, would be more severe for difficult discrimination tasks involving percep-tually similar odors.…”

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

“…In contrast to the spontaneous discrimination between odorants tested when a habituation task is used, discrimination in a rewarded forced-choice task was only affected when all NE receptors were blocked: similar results were obtained in two very different behavioral paradigms in mice (Doucette et al 2007) and rats (Mandairon et al 2008). The former study showed that in an automated successive go-no-go task, mice with all bulbar NE receptors blocked were significantly impaired in learning a discrimination between highly similar binary mixtures only.…”

α2-Adrenergic receptor activation promotes long-term potentiation at excitatory synapses in the mouse accessory olfactory bulb

“…Enhanced release of noradrenaline (NA) within the MOB plays an important role in long-term synaptic plasticity and odor learning in a variety of contexts. These include olfactory conditioning in neonatal rats (Sullivan et al 1989(Sullivan et al , 1992(Sullivan et al , 2000Harley et al 2006;Zhang et al 2010;Shakhawat et al 2012), the learning of newborn lamb odors after parturition in sheep (Pissonnier et al 1985), odor discrimination after memory formation in mice (Doucette et al 2007;Shea et al 2008;Moreno et al 2012), a specific long-term suppression of mitral cell (MC) responses to paired odors in mice (Shea et al 2008), a long-term reduction of paired-pulse inhibition in neonatal rats (Wilson and Leon 1988), long-term enhancement of synchronized γ frequency oscillations in rat MOB slices (Gire and Schoppa 2008;Pandipati et al 2010), long-term potentiation (LTP) of synaptic strength in rat MOB slices (Yuan 2009;Zhang et al 2010), and a long-term suppression of presynaptic input to MCs in mice (Eckmeier and Shea 2014).…”