Stimulation of the Locus Ceruleus Modulates Signal-to-Noise Ratio in the Olfactory Bulb.

Norepinephrine (NE) has been shown to influence sensory, and specifically olfactory processing at the behavioral and physiological levels, potentially by regulating signal-to-noise ratio (S/N). The present study is the first to look at NE modulation of olfactory bulb (OB) in regards to S/N in vivo We show, in male rats, that locus ceruleus stimulation and pharmacological infusions of NE into the OB modulate both spontaneous and odor-evoked neural responses. NE in the OB generated a non-monotonic dose-response relationship, suppressing mitral cell activity at high and low, but not intermediate, NE levels. We propose that NE enhances odor responses not through direct potentiation of the afferent signal per se, but rather by reducing the intrinsic noise of the system. This has important implications for the ways in which an animal interacts with its olfactory environment, particularly as the animal shifts from a relaxed to an alert behavioral state.SIGNIFICANCE STATEMENT Sensory perception can be modulated by behavioral states such as hunger, fear, stress, or a change in environmental context. Behavioral state often affects neural processing via the release of circulating neurochemicals such as hormones or neuromodulators. We here show that the neuromodulator norepinephrine modulates olfactory bulb spontaneous activity and odor responses so as to generate an increased signal-to-noise ratio at the output of the olfactory bulb. Our results help interpret and improve existing ideas for neural network mechanisms underlying behaviorally observed improvements in near-threshold odor detection and discrimination.

Stressors impair odor recognition memory via an olfactory bulb-dependent noradrenergic mechanism.

Non-associative habituation and odor recognition tasks have been widely used to probe questions of social recognition, odor memory duration, and odor memory specificity. Among others, these paradigms have provided valuable insight into how neuromodulation, and specifically norepinephrine/noradrenaline (NE) influences odor memory. In general, NE levels are modulated by arousal, stress, and behavioral state, but there is sparse evidence of a direct relationship between NE and odor memory in adult rodents. The present study uses simple mild psychological stressors (bright light and sound) to modulate NE levels physiologically in order to probe stressors NE-dependent effect on odor recognition memory. In rats with bilateral bulbar cannulations, we show that these stressors modulate olfactory memory and that this effect is at least partially mediated by the olfactory bulb. Specifically, we show that the presence of stressors during the acquisition of odor memory suppresses memory for an odor when tested 30 min after familiarization to that odor. This suppression is blocked by infusing NE antagonists into the olfactory bulb prior to odor acquisition. Additionally, we find that infusion of bulbar NE is sufficient to suppress odor memory in a manner mimicking that of our stressors. These effects are unlikely to be solely mediated by locomotor/exploratory changes produced by stressors, although these stressors influence certain behaviors not directly related to odor investigation. This study provides important information about how behaviorally relevant changes in NE can influence top-down sensory processing and odor memory.

Blocking muscarinic receptors in the olfactory bulb impairs performance on an olfactory short-term memory task.

Cholinergic inputs to cortical processing networks have long been associated with attentional and top-down processing. Experimental and theoretical studies suggest that cholinergic inputs to the main olfactory bulb (OB) can modulate both neural and behavioral odor discrimination. Previous experiments from our laboratory and others demonstrate that blockade of nicotinic receptors directly impairs olfactory discrimination, whereas blockade of muscarinic receptors only measurably impairs olfactory perception when task demands are made more challenging, such as when very low-concentration odors are used or rats are required to maintain sensory memory over long durations. To further investigate the role of muscarinic signaling in the OB, we developed an olfactory delayed match-to-sample task using a digging-based behavioral paradigm. We find that rats are able to maintain robust short-term odor memory for 10-100 s. To investigate the role of muscarinic signaling in task performance, we bilaterally infused scopolamine into the OB. We find that high dosages of scopolamine (38 mM) impair performance on the task across all delays tested, including the baseline condition with no delay, whereas lower dosages (7.6 mM and 22.8 mM) had no measureable effects. These results indicate that general execution of the match-to-sample task, even with no delay, is at least partially dependent on muscarinic signaling in the OB.