Abstract
The cholinergic system has extensive projections to the olfactory bulb (OB) where it produces a state-dependent regulation of sensory gating. Previous work has shown a prominent role of muscarinic acetylcholine (ACh) receptors (mAChRs) in regulating the excitability of OB neurons, in particular the M1 receptor. Here, we examined the contribution of M1 and M3 mAChR subtypes to olfactory processing using mice with a genetic deletion of these receptors, the M1−/− and the M1/M3−/− knockout (KO) mice. Genetic ablation of the M1 and M3 mAChRs resulted in a significant deficit in odor discrimination of closely related molecules, including stereoisomers. However, the discrimination of dissimilar molecules, social odors (e.g., urine) and novel object recognition was not affected. In addition the KO mice showed impaired learning in an associative odor-learning task, learning to discriminate odors at a slower rate, indicating that both short and long-term memory is disrupted by mAChR dysfunction. Interestingly, the KO mice exhibited decreased olfactory neurogenesis at younger ages, a deficit that was not maintained in older animals. In older animals, the olfactory deficit could be restored by increasing the number of new born neurons integrated into the OB after exposing them to an olfactory enriched environment, suggesting that muscarinic modulation and adult neurogenesis could be two different mechanism used by the olfactory system to improve olfactory processing.
Highlights
The detection and processing of chemosensory signals by the olfactory system enables a myriad of behaviors, such as food preferences, predator avoidance and social interactions, including keen recognition and mate selection (Sullivan et al, 2015)
Previous work has shown that cholinergic modulation of excitation of granule cells (GCs) in the olfactory bulb (OB) occurs mainly through activation of type M1 muscarinic acetylcholine (ACh) receptors (mAChRs) (Pressler et al, 2007; Smith and Araneda, 2010; Smith et al, 2015), the contribution of this receptor
Previous work has shown a prominent role of mAChRs, in particular the M1 receptor, in regulating the excitability of OB neurons (Pressler et al, 2007; Smith and Araneda, 2010; Smith et al, 2015)
Summary
The detection and processing of chemosensory signals by the olfactory system enables a myriad of behaviors, such as food preferences, predator avoidance and social interactions, including keen recognition and mate selection (Sullivan et al, 2015). These odor-triggered behaviors rely on the ability of olfactory circuits to experience short and long-term plasticity, enabling learning and recognition of new odors and the discrimination of salient odor stimuli against a background of less relevant odor cues. Inhibition of MCs by GCs is thought to contribute to neuronal computations in the OB including sparsening and feature binding of odor representations (Koulakov and Rinberg, 2011; Kato et al, 2012; Lepousez et al, 2013; Gschwend et al, 2015)
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