Abstract
The olfactory bulb (OB) receives significant cholinergic innervation and widely expresses cholinergic receptors. While acetylcholine (ACh) is essential for olfactory learning, the exact mechanisms by which ACh modulates olfactory learning and whether it is specifically required in the OB remains unknown. Using behavioral pharmacology and optogenetics, we investigated the role of OB ACh in a simple olfactory fear learning paradigm. We find that antagonizing muscarinic ACh receptors (mAChRs) in the OB during fear conditioning but not testing significantly reduces freezing to the conditioned odor, without altering olfactory abilities. Additionally, we demonstrate that m1 mAChRs, rather than m2, are required for acquisition of olfactory fear. Finally, using mice expressing channelrhodopsin in cholinergic neurons, we show that stimulating ACh release specifically in the OB during odor-shock pairing can strengthen olfactory fear learning. Together these results define a role for ACh in olfactory associative learning and OB glomerular plasticity.
Highlights
The olfactory bulb (OB) receives significant input from neuromodulatory centers that release norepinephrine, serotonin, and acetylcholine (ACh) into the OB, which can alter olfactory learning and associated plasticity (Wilson et al, 2004; Fletcher and Chen, 2010; Ross and Fletcher, 2019)
Using a combination of in vivo pharmacology and optogenetics in conjunction with olfactory fear conditioning, we investigated the role of ACh neurotransmission in olfactory fear learning
We aimed to determine whether muscarinic ACh receptors (mAChRs) in the OB are required for acquisition of olfactory fear
Summary
The olfactory bulb (OB) receives significant input from neuromodulatory centers that release norepinephrine, serotonin, and acetylcholine (ACh) into the OB, which can alter olfactory learning and associated plasticity (Wilson et al, 2004; Fletcher and Chen, 2010; Ross and Fletcher, 2019). The cholinergic projection neurons terminate densely in the glomerular layer (Shipley and Ennis, 1996) where odor information is first processed in the brain and represented in a spatiotemporal pattern of glomerular activation unique to each odor (Wachowiak and Cohen, 2001; Spors and Grinvald, 2002; Bozza et al, 2004; Mori et al, 2006; Fletcher et al, 2009; Storace and Cohen, 2017) Both nicotinic and muscarinic ACh receptor (mAChR) subtypes are widely expressed in the glomerular layer (Le Jeune et al, 1995; Castillo et al, 1999; Ghatpande and Gelperin, 2009; D’Souza and Vijayaraghavan, 2012) and have varied. Considering ACh is required for olfactory fear learning and its widespread innervation of the olfactory system, its role in olfactory fear learning and plasticity presents an interesting target for further investigation
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